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Contributors
Preface
Acknowledgments
Abbreviations
1 Psychotic Disorders
2 Bipolar Disorders
3 Depressive Disorders
4 Anxiety Disorders
5 Trauma and Stressor-Related Disorders and

Dissociative Disorders
6 Obsessive-Compulsive and Related Disorders
7 Eating Disorders
8 Neurodevelopmental Disorders and Child and

Adolescent Psychiatric Conditions
9 Neurocognitive Disorders
10 Substance-Related Disorders
11 Personality Disorders
12 Miscellaneous Disorders
13 Special Clinical Topics
14 Legal Issues
15 Antipsychotics
16 Antidepressants and Somatic Therapies
17 Mood Stabilizers
18 Anxiolytics
19 Miscellaneous Medications
20 Major Adverse Drug Reactions
21 Psychological Theory and Psychotherapy
Questions
Answers
Appendix
Index
Margaret Benningfield, MD
Assistant Professor of Psychiatry and Behavioral Sciences
Department of Psychiatry and Behavioral Sciences
Vanderbilt University School of Medicine
Nashville, Tennessee
Ramzi Mardam Bey, MD

Ronald L. Cowan, MD, PhD

Professor of Psychiatry and Behavioral Sciences
Professor of Radiology and Radiological Sciences
Professor of Psychology
Vanderbilt University
Sheryl Fleisch, MD
Bradley Freeman, MD
Associate Professor of Clinical Psychiatry and Behavioral Sciences
Sonia Matwin, PhD

Michael J. Murphy, MD, MPH

National Medical Director
Behavioral Health
Hospital Corporation of America
Adam Pendleton, MD, MBA

Fellow in Geriatric Psychiatry
Meghan Riddle, MD
Lloyd I. Sederer, MD
Chief Medical Officer
New York State Office of Mental Health
Adjunct Professor
Columbia/Mailman School of Public Health
Medical Editor for Mental Health
The Huffington Post
Contributing Writer
US News and World Report
New York, New York
Maja Skikic, MD
Jonathan Smith, MD
Fellow in Consultation-Liaison Psychiatry
Yasas Chandra Tanguturi, MBChB

Assistant Professor of Clinical Psychiatry and Behavioral Sciences
Jose Arriola Vigo, MD

Fellow in Consultation-Liaison Psychiatry
Edwin Williamson, MD
lueprints Psychiatry was conceived by a group of recent
B medical school graduates who saw that there was a need for a
thorough yet compact review of psychiatry that would adequately
prepare students for the USMLE yet would be digestible in small
pieces that busy residents can read during rare moments of calm
between busy hospital and clinical responsibilities. Many students
have reported that the book is also useful for the successful
completion of the core and advanced psychiatry clerkships. We
believe that the book provides a good overview of the field that the
student should supplement with more in-depth reading. Before
Blueprints Psychiatry, we felt that review books were either too
cursory to be adequate or too detailed in their coverage for busy
readers with little free time. We have kept the content current by
repeated updates and revisions of the book while retaining a
balance between comprehensiveness and brevity. This new edition
reflects changes in response to user feedback. The structure of the
book mirrors the major concepts and therapeutics of modern
psychiatric practice. We cover each major diagnostic category,
each major class of somatic and psychotherapeutic treatment, legal
issues, and special situations that are unique to the field. In this
edition, we have updated all diagnoses to those included in the
current Diagnostic and Statistical Manual, 5th edition (DSM-5) and
have included new images, 25% more USMLE study questions,
and a Neural Basis section for each major diagnostic category. We
recommend that those preparing for USMLE read the book in
chapter order but cross reference when helpful between diagnostic
and treatment chapters. We hope that Blueprints Psychiatry fits as
neatly into your study regimen as it fits into your backpack or
briefcase. You never know when you’ll have a free moment to
review for the boards!
Michael J. Murphy
Ronald L. Cowan
e would like to acknowledge the faculty, staff, medical
W students, and trainees of the Vanderbilt Psychiatric Hospital
and Vanderbilt University Medical Center for their contributions
and ongoing inspiration.
Michael J. Murphy
Ronald L. Cowan
AA Alcoholics anonymous
ABG Arterial blood gas
ACLS Advanced cardiac life support
ADHD Attention-deficit/hyperactivity disorder
ASP Antisocial personality disorder
BAL Blood alcohol level
BID Twice daily
CBC Complete blood count
CBT Cognitive-behavioral therapy
CNS Central nervous system
CO2 Carbon dioxide
CPR Cardiopulmonary resuscitation
CSF Cerebrospinal fluid
CT Computerized tomography
CVA Cerebrovascular accident
DBT Dialectical behavior therapy
DID Dissociative identity disorder
DT Delirium tremens
ECG Electrocardiogram
ECT Electroconvulsive therapy
EEG Electroencephalogram
EPS Extrapyramidal symptoms
EW Emergency ward
FBI Federal Bureau of Investigation
5HIAA 5-hydroxy indoleacetic acid
5HT 5-hydroxy tryptamine
GABA Gamma-amino butyric acid
GAD Generalized anxiety disorder
GHB Gamma-hydroxybutyrate
GI Gastrointestinal
HIV Human immunodeficiency virus
HPF High-power field
ICU Intensive care unit
IM Intramuscular
IPT Intrapersonal therapy
IQ Intelligence quotient
IV Intravenous
LP Lumbar puncture
LSD Lysergic acid diethylamine
MAOI Monoamine oxidase inhibitor
MCV Mean corpuscular volume
MDMA 3,4-methylenedioxy-methamphetamine
MR Mental retardation
MRI Magnetic resonance imaging
NIDA National Institute on Drug Abuse
NMS Neuroleptic malignant syndrome
OCD Obsessive-compulsive disorder
PCA Patient-controlled analgesia
PMN Polymorphonuclear leukocytes
PO By mouth
PTSD Posttraumatic stress disorder
QD Each day
REM Rapid eye movement
SES Socioeconomic status
SSRI Selective serotonin reuptake inhibitor
TCA Tricyclic antidepressant
TD Tardive dyskinesia
T4 Tetra-iodo thyronine
TID Three times daily
TSH Thyroid-stimulating hormone
T3 Tri-iodo thyronine
WBC White blood cell count
WISC-R Wechsler Intelligence Scale for Children–Revised
Psychotic disorders are a collection of disorders in which
psychosis, defined as a gross impairment in reality testing,
predominates the symptom complex. Psychotic symptoms are
characterized into five domains: hallucinations, delusions,
disorganized thought, disorganized or abnormal motor behavior,
and negative symptoms. Table 1-1 lists the Diagnostic and
Statistical Manual of Mental Disorders, Fifth edition (DSM-5)
classification of the psychotic disorders.
TABLE 1-1. Psychotic Disorders

Schizophrenia
Schizophreniform disorder
Schizoaffective disorder
Brief psychotic disorder
Schizotypal (personality) disorder
Delusional disorder
It is important to understand that primary psychotic disorders

are different from mood disorders with psychotic features and
drug-induced psychosis. Patients can present with a severe episode
of depression or mania and have delusions and hallucinations.
These patients do not have a primary psychotic disorder; rather,
their psychosis is secondary to a mood disorder.
The diagnoses described in this chapter are among the most
severely disabling of mental disorders. Disability is due in part to
the chronicity and the extreme degree of social and occupational
dysfunction associated with these disorders.
NEURAL BASIS
Much of our understanding of the neural basis for psychotic
disorders is based in research on schizophrenia. Schizophrenia is
currently considered a neurodevelopmental illness. Reduced
regional brain volume with enlarged cerebral ventricles is a
hallmark finding. Brain volume is reduced in limbic regions
including amygdala, hippocampus, and parahippocampal gyrus.
The prefrontal cortex microanatomy is altered. Thalamic and basal
ganglia regions are also affected. Altered dopamine function is
strongly implicated in positive and negative symptoms of
schizophrenia. An excess of dopamine in the mesolimbic pathway
is thought to contribute to the positive symptoms of schizophrenia,
whereas deficient dopamine function in the mesocortical pathways
is thought to contribute to the negative symptoms. γ-Aminobutyric
acid (GABA), glutamate, and the other monoamine
neurotransmitters are also likely affected.
SCHIZOPHRENIA
Schizophrenia is a disorder in which patients have psychotic
symptoms and social or occupational dysfunction that persists for
at least 6 months.
EPIDEMIOLOGY
Schizophrenia affects 1% of the population. The typical age of
onset is the late teens to the early 20s for men and the mid- to late
20s for women. Women are more likely to have a “first break” later
in life; in fact, about one-third of women have an onset of illness
after age 30, with a second peak occurring after menopause.
Schizophrenia is diagnosed disproportionately among the lower
socioeconomic classes; although theories exist for this finding,
none has been substantiated.
RISK FACTORS
Risk factors for schizophrenia include genetic risk factors (family
history), prenatal and perinatal factors such as difficulties or
infections during maternal pregnancy or delivery, winter births,
neurocognitive abnormalities such as low premorbid intelligence
quotient (IQ) or early childhood neurodevelopmental difficulties,
urban living, migration to a different culture, sexual trauma, and
cannabis use (especially in susceptible individuals).
ETIOLOGY
The etiology of schizophrenia is unknown. There is a clear
inheritable component, but familial incidence is sporadic, and
schizophrenia does occur in families with no history of the disease.
Schizophrenia is widely believed to be a neurodevelopmental
disorder. Multiple neuronal types and pathways appear to be
implicated, including those using the neurotransmitters dopamine,
glutamate, and GABA.
Dopamine
The most widely investigated theory for contributions to
schizophrenia is the dopamine hypothesis, which posits that
schizophrenia is due to hyperactivity in brain dopaminergic
pathways. This theory is consistent with the efficacy of
antipsychotics (which block dopamine receptors) (Fig. 1-1) and the
ability of drugs (such as cocaine or amphetamines) that stimulate
dopaminergic activity to induce psychosis. Postmortem studies
have also shown higher numbers of dopamine receptors in specific
subcortical nuclei of those with schizophrenia than in those with
normal brains.
FIGURE 1-1. Dopamine: For dopamine receptor type 2 (D2)

antagonist medications, the affinity with which the drug binds the D2
receptor predicts the drugs potency as an antipsychotic, supporting
the dopamine hypothesis of schizophrenia. (From Bear MF, Connors
BW, Paradiso MA. Neuroscience: Exploring the Brain, 4th ed.
Philadelphia, PA: Wolters Kluwer, 2015.)
Glutamate
Glutamate dysfunction may contribute to schizophrenia. Clinical
observations revealed that drugs (such as ketamine and
phencyclidine [PCP]) that block the N-methyl-d-aspartate (NMDA)
receptor channel can produce psychotic symptoms in humans (Fig.
1-2). Similarly, psychotic symptoms are prominent in individuals
with anti-NMDA encephalitis, an autoimmune condition associated
with antibodies directed against the NMDA receptor.
FIGURE 1-2. Glutamate: The drug phencyclidine (PCP) can block the
N-methyl-d-aspartate (NMDA) receptor channel and is associated with
hallucinations and paranoia in humans. Similarly, autoimmune
reactions against the NMDA receptor (known as anti-NMDA receptor
encephalitis) can produce a range of psychotic symptoms. (From Bear
MF, Connors BW, Paradiso MA. Neuroscience: Exploring the Brain,
4th ed. Philadelphia, PA: Wolters Kluwer, 2015.)
γ-Aminobutyric Acid
Alterations in prefrontal cortical GABA interneurons are most
strongly linked to cognitive impairments in schizophrenia. There
do not appear to be reductions in overall GABA interneurons in the
prefrontal cortex but the synthetic enzyme (GAD67) for GABA is
lower in a subset of these neurons, among other indicators of
altered GABA function such as altered GABA reuptake.
More recent studies have focused on structural and functional
abnormalities through brain imaging of patients with schizophrenia
and control populations. No one finding or theory to date suffices
to explain the etiology and pathogenesis of this complex disease.
CLINICAL MANIFESTATIONS
History and Mental Status Examination

Schizophrenia is a disorder characterized by symptoms that have
been termed positive and negative symptoms, by a pattern of
social and occupational deterioration, and by persistence of the
illness for at least 6 months. Positive symptoms are characterized
by the presence of unusual thoughts, perceptions, and behaviors
(e.g., hallucinations, delusions, agitation); negative symptoms are
characterized by the absence of normal social and mental functions
(e.g., lack of motivation, isolation, anergia, and poor self-care). The
positive versus negative distinction was made in a nosologic
attempt to identify subtypes of schizophrenia, as well as because
some medications seem to be more effective in treating negative
symptoms. Clinically, patients often exhibit both positive and
negative symptoms at the same time. Although subtypes of
schizophrenia are no longer recognized, it is worthwhile to note
that a preponderance of negative symptoms portends a poorer
prognosis. Table 1-2 lists common positive and negative
symptoms.
TABLE 1-2. Positive and Negative Symptoms of
Schizophrenia
Negative Symptoms
Affective Decreased expression of emotion, such as lack of

flattening or expressive gestures
blunting
Alogia Literally “lack of words,” including poverty of speech
and of speech content in response to a question
Avolition— Decreased energy toward self-care, work/school,
apathy movement
Positive Symptoms
Hallucinations Auditory, visual, tactile, or olfactory hallucinations;
voices that are commenting
Delusions Often described by content; persecutory, grandiose,
paranoid, religious; ideas of reference, thought
broadcasting, thought insertion, thought withdrawal
Bizarre Aggressive/agitated, odd clothing or appearance, odd
behavior social behavior, repetitive-stereotyped behavior
Based on Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock’s Concise Textbook of Clinical
Psychiatry. Philadelphia, PA: Wolters Kluwer, 2017.
To make the diagnosis (Table 1-3), two (or more) of the

following symptoms must be present: delusions, hallucinations,
disorganized speech, grossly disorganized or catatonic (mute or
posturing) behavior, or negative symptoms. At least one of the two
symptoms must be delusions, hallucinations, or disorganized
speech. There must also be social or occupational dysfunction. The
patient must be ill for at least 6 months, including prodromal
periods.
TABLE 1-3. 1-Diagnostic Criteria for Schizophrenia

Delusions At least one of the two criteria must come
Hallucinations from the first three
Disorganized speech
Grossly disorganized or
catatonic behavior
Negative symptoms
To diagnose schizophrenia, two symptoms from the above list must be
present for at least 1 month and at least one of the symptoms must come
from the first three. Symptoms must cause functional impairment and the
overall period of symptoms must be at least 6 months.
Patients with schizophrenia generally have a history of

abnormal premorbid functioning. The prodrome of schizophrenia
includes poor social skills, social withdrawal, and unusual
(although not frankly delusional) thinking, sometimes referred to as
magical thinking. Notably, there is a strong correlation between
schizotypal personality disorder and development of schizophrenia.
Inquiring about the premorbid history may help to distinguish
schizophrenia from a psychotic illness secondary to mania or drug
ingestion.
Patients with schizophrenia are at high risk for suicide.
Approximately 20% will attempt suicide, and 5% will complete
suicide. Risk factors for suicide include male gender, age younger
than 30 years, poor social support, chronic course, prior depression,
and recent hospital discharge.
Diagnostic Evaluation
The diagnostic evaluation for schizophrenia involves a detailed
history, physical, and laboratory examination, preferably including
brain magnetic resonance imaging (MRI). Although there is no
diagnostic laboratory or imaging finding for schizophrenia,
cerebral ventricular enlargement is typical. Medical causes, such as
neuroendocrine abnormalities and psychostimulant use disorder,
and such brain insults as tumors or infection, should be ruled out.
DIFFERENTIAL DIAGNOSIS
The differential diagnosis of an acute psychotic episode is broad
and challenging (Table 1-4). Once a medical or substance-related
condition has been ruled out, the task is to differentiate
schizophrenia from a schizoaffective disorder, a mood disorder
with psychotic features, a delusional disorder, or a personality
disorder.
TABLE 1-4. Causes of Acute Psychotic Syndromes

Major Psychiatric Disorders
Acute exacerbation of Depression with psychotic features
schizophrenia
Atypical psychoses Mania
(e.g., schizophreniform)
Drug Use and Withdrawal
Alcohol withdrawal Phencyclidine (PCP) and hallucinogen use
Amphetamines and Sedative-hypnotic withdrawal
cocaine use
Prescription Drugs
Anticholinergic agents
Digitalis toxicity
Glucocorticoids and adrenocorticotropic hormone (ACTH)
Isoniazid
l-DOPA (3,4-dihydroxy-l-phenylalanine) and other dopamine agonists
Nonsteroidal anti-inflammatory agents
Withdrawal from monoamine oxidase inhibitors (MAOIs)
Other Toxic Agents
Carbon disulfide Heavy metals
Neurologic Causes
AIDS encephalopathy Infectious viral encephalitis
Brain tumor Lupus cerebritis
Complex partial Neurosyphilis
seizures
Early Alzheimer’s or Stroke
Pick’s disease
Huntington’s disease Wilson’s disease
Hypoxic
encephalopathy
Metabolic Causes
Acute intermittent Hypo- and hypercalcemia
porphyria
Cushing’s syndrome Hypo- and hyperthyroidism
Early hepatic Paraneoplastic syndromes (anti-NMDA [N-
encephalopathy methyl d-aspartate] receptor encephalitis;
limbic encephalitis)
Nutritional Causes
Niacin deficiency Vitamin B12 deficiency
(pellagra)
Thiamine deficiency
(Wernicke-Korsakoff’s
syndrome)
From Rosenbaum JF, Arana GW, Hyman SE, et al. Handbook of Psychiatric Drug Therapy, 5th ed.
Philadelphia, PA: Lippincott Williams & Wilkins, 2005.
MANAGEMENT
Antipsychotic agents are primarily used in treatment. These
medications are used to treat acute psychotic episodes and to
maintain patients in remission or with long-term illness.
Antipsychotic medications are discussed in Chapter 15.
Combinations of several classes of medications are often
prescribed in severe or refractory cases. Psychosocial treatments,
including stable reality-oriented psychotherapy with increasing
support for cognitive behavioral therapy, family support,
psychoeducation, social and vocational skills training, and attention
to details of living situation (housing, roommates, daily activities)
are critical to the long-term management of these patients.
Complications of schizophrenia include those related to
antipsychotic medications, secondary consequences of poor health
care and impaired ability to care for oneself, and increased rates of
suicide. Once diagnosed, schizophrenia is a long-term
remitting/relapsing disorder with impaired interepisode function.
Poorer prognosis occurs with early onset, a history of head trauma,
or comorbid substance abuse.
SCHIZOAFFECTIVE DISORDER
Patients with schizoaffective disorder have psychotic episodes that
resemble schizophrenia but with prominent mood
disturbances. Their psychotic symptoms, however, must persist
for at least 2 weeks in the absence of any mood syndrome.
EPIDEMIOLOGY
Lifetime prevalence is estimated at 0.5% to 0.8%. Age of onset is
similar to schizophrenia (late teens to early 20s).
RISK FACTORS
Risk factors for schizoaffective disorder are not well established
but likely overlap with those of schizophrenia and affective
disorders.
ETIOLOGY
The etiology of schizoaffective disorder is unknown. It may be a
variant of schizophrenia, a variant of a mood disorder, a distinct
psychotic syndrome, or simply a superimposed mood disorder and
psychotic disorder.

Patients with schizoaffective disorder meet the diagnostic criteria
for psychotic symptoms of schizophrenia and also meet criteria for
a major mood disturbance (mania or major depressive episode).
They must also have periods of at least 2 weeks during some point
in their illness in which they have psychotic symptoms (delusions
or hallucinations) without a major mood disturbance. Mood
disturbances need to be present for a substantial portion of the
illness.
There are two subtypes of schizoaffective disorder recognized
in the DSM-5, depressive type and bipolar type, which are
determined by the nature of the mood disturbance episodes.
The diagnostic evaluation for schizoaffective disorder is similar to
other psychiatric conditions and involves a detailed history,
physical, and laboratory examination, preferably including brain
magnetic resonance imaging. Medical conditions producing
secondary behavioral symptoms should be ruled out.
Mood disorders (depressive or bipolar disorders) with psychotic
features, as in mania or psychotic depression, are different from
schizoaffective disorder in that patients with schizoaffective
disorder have persistence (for at least 2 weeks) of the psychotic
symptoms after the mood symptoms have resolved. Schizophrenia
is differentiated from schizoaffective disorder by the absence of a
prominent mood disorder in the course of the illness.
It is important to distinguish the prominent negative symptoms
of the patient with schizophrenia from the lack of energy or
anhedonia in the depressed patient with schizoaffective disorder.
More distinct symptoms of a mood disturbance (such as depressed
mood and sleep disturbance) should indicate a true coincident
mood disturbance.
MANAGEMENT
Patients are treated with medications that target the psychosis and
the mood disorder. Typically, these patients require the
combination of an antipsychotic medication and a mood
stabilizer. Mood stabilizers are described in Chapter 17. An
antidepressant or electroconvulsive therapy may be needed for an
acute depressive episode. Psychosocial treatments are similar for
schizoaffective disorder and schizophrenia. Complications of
schizoaffective disorder include those related to antipsychotic and
mood stabilizer medications, secondary consequences of poor
health care and impaired ability to care for oneself, and increased
rates of suicide. Prognosis is better than for schizophrenia and
worse than for bipolar disorder or major depression. Patients with
schizoaffective disorder are more likely than those with
schizophrenia but less likely than mood-disordered patients to have
a remission after treatment.
SCHIZOPHRENIFORM DISORDER
Essentially, schizophreniform disorder is diagnosed when an
individual has symptoms of schizophrenia that last between 1 and 6
months. The diagnostic criteria do not require the presence of
impaired social or occupational functioning, although they can be
present.
EPIDEMIOLOGY
Outcome studies of this disorder indicate that about one-third of the
patients recover but most of the remaining two-thirds are ultimately
diagnosed with schizophrenia or schizoaffective disorder. The
diagnosis of schizophreniform disorder may help avoid premature
diagnosis of patients with schizophrenia before some other
disorder, such as bipolar disorder, manifests itself.
RISK FACTORS
Because most patients with schizophreniform disorder are
eventually diagnosed with schizophrenia, risk factors are likely
similar for the two groups.
ETIOLOGY
At this time, the etiology is unknown. At least one study found
similarities in brain structure abnormalities between patients with
schizophrenia and those with schizophreniform disorder.

Schizophreniform disorder is essentially short-course
schizophrenia without the requirement of social withdrawal and
occupational impairment. Patients with this disorder have what
appears to be an episode of schizophrenia, including delusions,
hallucinations, disorganized speech, or negative symptoms, but the
duration of illness including prodromal, active, and residual phases
is from 1 to 6 months. The diagnosis changes to schizophrenia if
the symptoms extend past 6 months, even if only residual
symptoms are left.
Care must be taken to distinguish schizophreniform disorder from a
manic or depressive episode with psychotic features. Other causes
of an acute psychosis must be ruled out (substance-induced or due
to a general medical condition).
MANAGEMENT
The disorder is by definition self-limited. When symptoms cause
severe impairment, treatment is similar to that for the acute
treatment of psychosis in schizophrenia.
BRIEF PSYCHOTIC DISORDER

In brief psychotic disorder, the patient experiences a full psychotic
episode that is short lived. It can be temporally related to some
stressor or occur postpartum, but it is also seen without any
apparent antecedent.
EPIDEMIOLOGY
This condition is twice as common in females. The average onset is
in ones in their mid-30s.
ETIOLOGY
Although the etiology is unknown, the disorder seems to be
associated with borderline personality disorder and schizotypal
personality disorder.

In brief psychotic disorder, the patient develops psychotic
symptoms that last for at least 1 day but no more than 1 month,
followed by eventual return to premorbid functioning. Patients can
exhibit any combination of delusions, hallucinations, disorganized
speech, or grossly disorganized behavior. There are three
recognized subtypes: with marked stressors (formerly known as
brief reactive psychosis), without marked stressors, and
postpartum onset (if onset is during pregnancy or within 4 weeks
after delivery). Patients with the postpartum onset typically develop
symptoms within 1 to 2 weeks after delivery that resolve within 2
to 3 months.
It is important to rule out schizophrenia, especially if the disorder
worsens or persists for more than a month. A mood disorder such
as mania or depression with psychotic features must be ruled out.
MANAGEMENT
Hospitalization may be necessary to protect the patient. Treatment
with antipsychotics is common, although the condition is by
definition self-limited, and no specific treatment is required. The
containing environment of the hospital milieu may be sufficient to
help the patient recover.
DELUSIONAL DISORDER
Delusional disorder is characterized by delusions lasting 1 month
or more without other psychotic symptoms. It is rare, its course is
long term, and treatment is supportive.
EPIDEMIOLOGY
This disorder is rare, with a prevalence of 0.2%. Generally, onset is
in middle to late life. Its course is generally long term with
remission uncommon.
ETIOLOGY
The etiology is unknown. Often, psychosocial stressors appear to
be etiologic, for example, following migration. In migration
psychosis, the recently immigrated person develops persecutory
delusions. Many patients with delusional disorder have a paranoid
character premorbidly. Paranoid personality disorder has been
found in families of patients with delusional disorder.

This disorder is characterized by well-systematized delusions,
which are fixed beliefs that do not change in the face of
contradictory evidence. The delusions are nonbizarre if they could
happen in real life (such as being followed, poisoned, infected,
loved at a distance, having a disease, or being deceived by one’s
spouse or significant other). Delusions are considered bizarre if
they don’t align with ordinary life experiences. The delusions must
be present for at least 1 month. Other than the delusion, the
patient’s social adjustment may be normal.
The patient must not meet criteria for schizophrenia. Any mood
disorder must be brief relative to the duration of the illness. The
DSM-5 recognizes seven subtypes of delusional disorder (Table 1-
5).
TABLE 1-5. Delusional Disorder Subtypes

Erotomanic A person becomes falsely convinced that another person is
in love with him or her.
Grandiose A person becomes falsely convinced that he or she has
special abilities or is in other ways much more important
than reality indicates.
Jealous A person becomes falsely convinced that his or her lover is
unfaithful.
Persecutory A person becomes falsely convinced that others are out to
harm him or her and that he or she is being conspired
against in general.
Somatic A person becomes falsely convinced that he or she has a
bodily function disorder, for example, organ dysfunction,
body odor, or parasite infection.
Mixed A person is so diagnosed when no single delusional theme
predominates.
Unspecified A person is so diagnosed when a single delusional theme
cannot be determined or when the predominant delusional
theme does not match subtype criteria.
It is important to rule out other psychiatric or medical illnesses that
could have caused the delusions. Thereafter, delusional disorder
must be distinguished from major depression with psychotic
features, mania, schizophrenia, and paranoid personality.
MANAGEMENT
Trials of antipsychotics are appropriate but are often ineffective.
The primary treatment is psychotherapy, taking care neither to
support nor to refute the delusion but to maintain an alliance with
the patient. Without such an alliance, most patients fall out of
treatment; with an alliance, over time, the patient may relinquish
the delusions.
CATATONIA
Catatonia is a condition that is not restricted to schizophrenia or
psychotic disorders but that can occur in association with other
mental disorders, medical conditions, or conditions of unclear
origin.
Catatonia is a complex neuropsychiatric syndrome that involves
motor, speech, and attentional abnormalities and occurs in the
context of a psychiatric illness, substance use, or general medical
condition. Originally thought to be a complication of
schizophrenia, it is now recognized in mood disorders, in substance
use disorders, and in response to brain trauma or medical
conditions that affect the central nervous system. Although the
presentation can vary, it can present similarly regardless of
etiology.
EPIDEMIOLOGY
Catatonia occurs in 10% to 15% of patients with psychosis and
mood disorders. However, given the severity of the syndrome and
the fact that it can occur suddenly in a patient with no history of
catatonia, it should always be considered in situations where there
are speech or motor abnormalities consistent with the syndrome.
RISK FACTORS
The main risk factors include prior history of catatonia, history of a
mood or psychotic disorder, autism, recent physical or mental
trauma, inflammation or other physical perturbation of the nervous
system.
Catatonia most commonly manifests with mutism and slowed or
absent body movements. However, some patients present with
excessive or unusual motor activity or gestures. “Posturing”—
assuming a part of the body, usually a limb in a contorted, fixed
position—is a classic symptom. Motor disturbances can be
complete stupor, catalepsy, or waxy flexibility (movement of a
limb that stays in position). Sudden bursts of excessive activity
alternating with motionlessness can occur. The behavior is
generally considered to be involuntary, though some actions may
seem purposeful (such as acting opposite of a command, known as
negativism). The DSM-5 criteria require that 3 of the 12 recognized
symptoms (Table 1-6) be present to make the diagnosis. Catatonia
can worsen to the point of a systemic illness characterized by
severe muscle rigidity, hyperpyrexia, and autonomic instability.
This severe catatonia is malignant and, if untreated, may result in
death.
TABLE 1-6. Symptoms of Catatonia

Stupor
Catalepsy
Waxy flexibility
Mutism
Negativism
Posturing
Mannerism
Stereotypy
Agitation
Grimacing
Echolalia
Echopraxia

Taking a careful history from collateral sources is important given
that the patient is not able to relay the history. Asking about recent
physical symptoms, medical diagnoses, surgical procedures, falls,
or head trauma are important to rule out medical causes. A full
psychiatric history including social and developmental history
should be obtained. Prior history of neurologic symptoms may be
relevant. Family history of psychiatric illness and/or catatonia is an
important factor. In addition to a full physical examination, a
focused neurologic exam to the degree that the patient can
cooperate should focus on the key symptoms and signs of
catatonia.
The main diagnostic tool for determining the diagnosis is a
systematic examination of the movement and testing for negativism
as well as waxy flexibility and catalepsy. Brain imaging is only
helpful if there is a concern for an intracranial lesion.
Electroencephalographic examination is nonspecific in catatonia.
Blood tests are useful to rule out infectious and inflammatory
processes. Rarely, a patient can have evidence of anti-NMDA
antibodies causing an encephalitis leading to the catatonic
presentation. Although not part of the DSM-5 criteria, in clinical
practice, improvement following benzodiazepine administration is
often considered diagnostic of a catatonic state if other conditions
are met.
The differential diagnosis includes psychotic behavior mimicking
some catatonic features, such as malingering in a patient who is
clever enough to know the symptoms. Neuroleptic malignant
syndrome would be considered if the patient becomes rigid, febrile,
and medically unstable. Severe depression, severe anxiety, and
negative symptoms of schizophrenia can all lead to mutism,
staring, and minimal responsiveness, but at least two other features
must be present to diagnose catatonia. Underlying medical
conditions must always be ruled out.
MANAGEMENT
Patients who are catatonic can respond dramatically to acute doses
of benzodiazepines, particularly when injected intramuscularly or
administered intravenously. However, some patients may need
large dosages to achieve results. Often, the effect wanes as the
medication starts to be metabolized. If an underlying medical
condition is suspected of being the cause, treating that condition
can reverse the catatonia. If response to a regularly scheduled
benzodiazepine dosage starts to fade, it may be necessary to raise
the dosage to higher than usually prescribed. Patients with severe
catatonia have required four to five times the usual dosage or
greater to achieve a response. In some cases, it is necessary to treat
with electroconvulsive therapy (ECT). This treatment seems to
have a similarly robust effect on catatonia and also can treat some
of the underlying psychiatric conditions.
PROGNOSIS
The prognosis for most patients with catatonia is good. Once
properly diagnosed, the condition usually responds well to
treatment. Some patients will have recurrences of the syndrome,
and occasionally patients require ongoing maintenance therapy to
stay in remission. This usually involves maintenance ECT in these
cases.
KEY POINTS
Schizophrenia is characterized by psychosis and
social/occupational dysfunction that lasts for at
least 6 months.
Schizophrenia has a 10% suicide rate
(approximately one-third attempt suicide).
Schizophrenia is treated with antipsychotics,
cognitive behavior therapy, and psychosocial
support.
In schizoaffective disorder, there are mood
disturbances with psychotic episodes and there
are periods of psychosis without a mood
disturbance.
Schizoaffective disorder is treated with
antipsychotics and mood stabilizers.
The prognosis for schizoaffective disorder is better
than for schizophrenia but worse than for a mood
disorder.
Schizophreniform disorder resembles
schizophrenia but resolves completely in less than
6 months (roughly two-thirds progress to
schizophrenia or bipolar disorder).
Delusional disorder is characterized by delusions
and is long-term and unremitting.
Brief psychotic disorder is characterized by typical
psychotic symptoms lasting from 1 to 30 days.
Brief psychotic disorder can be preceded by a
stressor and can occur postpartum.
CLINICAL VIGNETTES
VIGNETTE 1
A 23-year-old African American man is brought to the emergency
department by the local police because of being disruptive on a public
street. He was allegedly yelling at a wall as if there were people in the
wall. He was shirtless and shoeless when picked up by the police. An
adjacent store owner who said he was behaving in a threatening
manner to his customers called the law enforcement. The officers
apprehended him, and, knowing that he suffers from mental illness,
brought him to the emergency room (ER) for evaluation. You are the
first doctor to assess him in the ER and find him sitting in recliner in
the psychiatric area of the ER. He appears disheveled and frustrated.
He doesn’t answer your questions until you sit down next to him and
then he starts to tell you about the voices he is hearing. Records
indicate that he has presented several times in a similar manner since
he became ill at age 17. He reports smoking marijuana daily and also
using some synthetic drugs. It also appears from his record that he
does not usually take medication consistently. His vital signs are
within normal limits. His complete blood count is normal and his CK is
elevated at 100.
1. What diagnosis is least likely on the differential diagnosis list?

a. Schizophrenia
b. Schizoaffective disorder
c. Substance-induced psychotic disorder
d. Bipolar disorder
e. Agoraphobia
2. Which of the following criteria are NOT used to make a diagnosis

of schizophrenia?
a. Auditory hallucinations
b. Delusions
c. Suicidal thoughts
d. Disorganized behavior
e. Negative symptoms
3. If the patient has a positive urine drug screen for

tetrahydrocannabinol (THC) but the patient has presented
repeatedly in the past with psychosis and a normal urine drug
screen, the most likely primary diagnosis is:
a. Delusional disorder
b. Brief psychotic disorder
c. Cannabis-induced psychotic disorder
d. Schizophrenia
e. Cannabis use disorder
VIGNETTE 2
A 36-year-old single white male who lives alone presents to a primary
care office complaining that a woman who lives in the apartment
above him is spying on him through “pinholes” in the ceiling of his
apartment. He reports that she moved in 2 years ago just after the
death of his mother and that his concerns began almost immediately
after that. He says that he has trouble sleeping feeling like she is
watching him and feels that he has no privacy. He thinks that she just
wants to see him naked and laugh at him. He has gone to the landlord
about it but he has not done anything. The landlord told him that it
would be impossible to do what he claims given the structure of the
building. But the patient insists that is true. You ask a psychologist in
your office to evaluate him further. He reports back that the patient
has had difficulty forming adult sexual relationships and was very
close with his mother until she died. He reports that there are no other
symptoms–no hallucinations, other odd beliefs or problems with self-
care. The patient has a job as an accountant with a small business in
town and has some friends in the area with whom he attends movies
and concerts for recreation. He has dated some females but has not
established any long-term relationships.
1. The most likely diagnosis is:

a. Brief psychotic disorder
b. Schizophrenia
c. Delusional disorder
d. Somatoform disorder
e. Autism spectrum disorder
2. The least likely diagnosis on the differential diagnosis is:

a. Obsessive-compulsive disorder
b. Delirium
c. Schizophrenia
d. Bipolar disorder
e. Panic disorder
3. The prognosis with treatment is:

a. Poor due to the tendency to develop more delusional beliefs
and hallucinations.
b. Poor due to the co-occurrence of substance abuse.
c. Guarded due to the chronic stable nature of the disorder.
d. Good due to the good response to pharmacotherapy.
e. Excellent due to the high rate of spontaneous remission.
ANSWERS
VIGNETE 1 Question 1
1. Answer E:
The patient presents with signs and symptoms that could be
consistent with schizophrenia, schizoaffective disorder, bipolar
disorder, and substance-induced psychotic disorder. Agoraphobia
would present with excessive fear, anxiety, and social avoidance,
none of which are characteristics of this presentation. The patient has
had symptoms for several years, and so brief psychotic disorder would
not be in the differential because this condition persists for less than 1
month. A diagnosis of schizophrenia can be made even in the
presence of use of drugs that might cause psychosis if the patient’s
history indicates that the psychotic symptoms preceded drug use or
that they persist well beyond the expected period of drug effects.
Psychoactive substance use is very commonly comorbid with
schizophrenia. Schizoaffective disorder would be considered if the
patient had prominent mood symptoms such as mania or severe
depression and the psychotic symptoms persisted for at least 2 weeks
during periods in which mood was euthymic.
2. Answer C:
The patient presents with classic symptoms of schizophrenia,
including delusions, hallucinations (voices), disorganized behavior
(talking to the wall), and negative symptoms (poorly groomed and not
fully dressed). About 20% of patients with schizophrenia attempt
suicide at some point in their illness with an overall 5% rate of
completed suicide this is not a diagnostic feature of the condition.
Suicide rates are increased across many psychiatric conditions.
Appropriate treatment is thought to reduce the risk of suicide although
among the antipsychotic medications, only clozapine has
demonstrated a clear effect on reducing suicidal ideation and suicide
attempts.
3. Answer D:
Although you would need to know more details of the timing of the
onset of the patient’s illness and his prior drug use patterns, the
available evidence supports schizophrenia as the most likely
diagnosis. Given a positive urine drug screen for THC, the patient has
recently used cannabis, which may be a trigger for relapse but the
global symptoms do not occur exclusively in the presence of the
substance. Although the patient presents with delusions, the presence
of hallucinations and disorganized behavior makes delusional disorder
inadequate to explain the symptom profile. His recurrent bouts of
psychosis are inconsistent with brief psychotic disorder because they
have persisted for over 1 year and brief psychotic disorder duration is
less than 1 month. In addition, the patient may have a cannabis use
disorder but his primary diagnosis would be consistent with
schizophrenia. Cannabis use is very common in patients with
psychosis and is thought to unmask or amplify the severity of
symptoms.
1. Answer C:
Given the patient’s apparent persistence of the delusional belief for
about 2 years, a brief psychotic disorder is ruled out because the time
course for brief psychotic disorder is less than 1-month duration.
Delusional disorder is characterized by well-systematized delusions,
which are fixed false beliefs. The delusions are nonbizarre if they
could happen in real life (such as being followed, poisoned, infected,
loved at a distance, having a disease, or being deceived by one’s
spouse or significant other). Delusions are considered bizarre if they
don’t align with ordinary life experiences. In this case, the patient has
nonbizarre delusions. The delusions must be present for at least 1
month. Other than the delusion, the patient’s social adjustment may
be normal. Because he does not exhibit other psychotic symptoms
(e.g., positive symptoms such as auditory or visual hallucinations or
negative symptoms such as lack of motivation, isolation, anergia, and
poor self-care), he fails to meet criteria for a schizophrenia diagnosis.
Although he is preoccupied with the notion that the neighbor is spying
on his body, he does not appear to have primary concerns about the
appearance of his body that are out of the ordinary as would be seen
in an obsessive-compulsive disorder, such as body dysmorphic
disorder. Finally, although he seems to have a somewhat restricted
life, he does not exhibit impaired social communication and
interactions, or a repetitive or restricted repertoire of activities and
interests characteristic of a patient with autism spectrum disorder.
2. Answer E:
The patient could be suffering from an obsession (as opposed to a
psychosis) if he exhibited the capacity to discern reality from fantasy
(intact reality testing) regarding the fear of being spied on and did not
believe that his neighbor was actually spying on him, but instead had
an obsessional worry that it might be occurring. Delirium is not
common in otherwise healthy 36-year-olds except in cases of drug
intoxication or withdrawal. However, delirium can present with
delusions or hallucinations and if the patient was confused or had
waxing and waning levels of arousal, disorientation, or impaired
attention, a delirium could explain the symptoms, albeit not for such a
long duration. His belief about the neighbor could be part of a larger
delusional system with hallucinations and aberrant functioning,
consistent with schizophrenia, but evidence is not provided for the full
criteria at this point. Similarly, the delusion could be secondary to a
bipolar manic episode with psychotic symptoms but this diagnosis
would require additional history of marked mood disturbances.
Although the fear of being spied on could result in anxiety, it is not
characteristic of panic disorder, which is characterized by recurrent,
unexpected panic attacks that can occur with or without agoraphobia.
Panic attacks typically come on suddenly, peak within minutes, and
last 5 to 30 minutes. Since no evidence for panic symptoms is
provided, this would not be on the differential diagnosis.
3. Answer C:
Guarded due to the chronic stable nature of the disorder is the
prognosis with treatment. Delusional disorder tends to remain fixed
and stable, neither worsening nor improving in most patients. The
primary treatment is psychotherapy, taking care neither to support nor
to refute the delusion but to maintain an alliance with the patient.
Without such an alliance, most patients fall out of treatment; with an
alliance, over time, the patient may relinquish the delusions. A small
percentage of patients will go on to develop a more global psychotic
disorder such as schizophrenia, but most do not. Substance abuse is
not a common co-occurring diagnosis. Unfortunately, patients rarely
remit spontaneously. Medication can be effective when patients agree
to a trial, with about a third to one-half showing significant
improvement following treatment with antipsychotic medication. If the
patient does not have insight into the delusional nature of symptoms,
medication adherence is less likely.
Bipolar disorders are a type of mood disorders. Mood is a
persistent emotional state (as differentiated from affect, which is
the external display of feelings). The Diagnostic and Statistical
Manual of Mental Disorders, Fifth edition (DSM-5) separated the
classification of mood disorders into depressive disorders and
bipolar and related disorders. The bipolar disorders are bipolar I
disorder, bipolar II disorder, and cyclothymic disorder, in addition
to bipolar disorder due to substance use or medication and bipolar
disorder due to another medical condition (Table 2-1). Bipolar
disorders are cyclic (usually over a period of weeks to months) and
recurrent.
TABLE 2-1. Bipolar Disorders

Bipolar I disorder
Bipolar II disorder
Cyclothymia
Substance/medication-induced bipolar disorder
Bipolar disorder due to another medical condition
NEURAL BASIS
The neural basis of bipolar disorders, and of mood disorders in
general, is not well understood. Because bipolar disorders most
commonly consist of elevated mood (mania and hypomania) and
depression, some neural substrates affected in bipolar disorder
overlap with those implicated in depressive disorders discussed in
Chapter 3 (see Fig. 3-1). In particular, emerging findings suggest
deficits in ventrolateral and orbitofrontal prefrontal cortex
connections with the amygdala, along with abnormal function and
lower brain volume in these regions. In addition, neural circuitry
mediating sleep–wake cycles and circadian rhythms are involved in
bipolar disorders. At the neurotransmitter level, monoamine
function (dopamine, norepinephrine, and serotonin), γ-
aminobutyric acid (GABA), and glutamate are implicated.
BIPOLAR I DISORDER
Bipolar I disorder is the most serious of the bipolar disorders and is
diagnosed after at least one episode of mania (Table 2-2). A manic
episode is diagnosed according to DSM-5 when a person
experiences a change in mood that is different from his or her
baseline or usual mood, and increased energy and activity. Patients
or their family and friends may notice an abrupt change with
elevated mood or irritable mood and increased physical activity.
DSM-5 criteria for manic episode require that the mood and energy
change last at least 1 week and be present most of the day.
Additional criteria for manic episode include alterations in at least
three areas, including self-esteem (increased self-esteem or
grandiosity), sleep (decreased need for sleep), speech (increased or
pressured), thoughts (racing or disorganized), attention (increased
distractability), activity (increased goal-directed activity), and
behavior (taking part in activities that are potentially risky).
Patients with bipolar I disorder typically also experience major
depressive episodes in the course of their lives.
TABLE 2-2. Bipolar I Disorder

MoodEnergy Change in mood (elevated or irritable) and increased
and activity activity from baseline.
Self-esteem At least three symptoms involving self-esteem, sleep,
Sleep speech, thoughts, attention, activity, and behavior are also
Speech required.
Thoughts
Attention
Activity
Behavior
EPIDEMIOLOGY
The lifetime prevalence is 0.4% to 1.6%, and the male-to-female
ratio is 1:1. There are no racial variations in incidence.
ETIOLOGY
Genetic and familial studies reveal that bipolar I disorder is
associated with increased bipolar I, bipolar II, and major depressive
disorders in first-degree relatives. Candidate genes involved in
bipolar disorder have been studied extensively, but no single gene
has been identified. Genetic susceptibility appears to involve the
interaction of many genes with small effects rather than a single
gene with a major effect. Genome-wide association studies have
found that several genetic variants are associated with bipolar
disorder. Mania can be precipitated by psychosocial stressors, and
there is evidence that sleep–wake cycle perturbations may
predispose a person to mania.
Bipolar I disorder is defined by the occurrence of mania (or a
mixed episode). A single manic episode is sufficient to meet
diagnostic requirements. Most patients, however, have recurrent
episodes of mania typically intermixed with depressive episodes.
The criteria for a manic episode are outlined in Table 2-2.
The first episode of mania usually occurs in the patient’s early
20s. Manic episodes are typically briefer than depressive episodes.
The transition between manic and major depressive episodes
occurs without an intervening period of euthymia in about two-
thirds of patients (Fig. 2-1A). Lifetime suicide rates range from
10% to 15%.
FIGURE 2-1. Bipolar mood disorders. (A) Bipolar I disorder. (B)
Bipolar II disorder. (C) Cyclothymic disorder.
Children can present with bipolar disorder that resembles the

adult type but differs according to age and developmental level.
Very young children might present with uncontrollable giggling,
slightly older children might try to teach their grammar school
class in the presence of their teacher, and adolescents might present
with severe anger outbursts and agitation. Co-occurring psychiatric
problems and psychosocial difficulties are the norm. Most children
with bipolar disorder have more than one relative with the
condition. A first manic episode in elderly individuals is
uncommon. Medical or neurologic causes of new bipolar disorder
in an older person should be thoroughly investigated.
Differential Diagnosis
Mania may be induced by antidepressants, stimulants,
electroconvulsive therapy (ECT), and phototherapy. When this
occurs, the patient is diagnosed with a substance/medication-
induced bipolar and related disorder, not bipolar I disorder, unless
the symptoms persist beyond what would be expected for the
duration of the influence of the causative agent. Bipolar and related
disorder due to another medical condition is the other major
differential diagnosis. Schizoaffective disorder, borderline
personality disorder, and major depressive disorder with agitation
are also considerations.
MANAGEMENT
Individuals experiencing a manic episode often have poor insight
and resist treatment. Pharmacologic interventions for acute mania
include antipsychotics in conjunction with benzodiazepines (for
rapid tranquilization) and initiation of mood stabilizers.
Antipsychotics are frequently used in mania with and without
psychotic features. Lithium is the most commonly used mood
stabilizer, but valproic acid is also effective. Carbamazepine,
lamotrigine, gabapentin, and long-acting benzodiazepines are used
if first-line treatments fail. Some atypical antipsychotics,
particularly clozapine, quetiapine, olanzapine, and aripiprazole, act
as mood stabilizers and are increasingly being used for
maintenance of bipolar disorder. ECT for manic, mixed, or
depressed episodes is used in patients with medication intolerance
and when a more immediate response is needed (e.g., to treat a
severely suicidal patient). For patients who have a history of
multiple recurrences or have a partial but inadequate response to a
maintenance drug that is tolerated, adding a second medication is
recommended. Common combinations include lithium or
valproate, plus a second-generation antipsychotic, such as
quetiapine, long-acting injectable risperidone, ziprasidone, or
olanzapine. Other combinations that are useful include lithium plus
valproate or carbamazepine. Children and adolescents are treated
with medications similar to those of adults.
Mood stabilizer maintenance therapy is essential in preventing
the recurrence of mania and appears to decrease the recurrence of
major depressive episodes. Psychotherapy is used to encourage
medication compliance, to help patients come to terms with their
illness, and to help repair some of the interpersonal damage done
while ill (e.g., infidelity, hostility, squandering money). Care must
be taken when prescribing antidepressants for major depressive
episodes or depressive episodes because of their potential role in
prompting more severe or more frequent manic episodes.
BIPOLAR II DISORDER
Bipolar II disorder is similar to bipolar I disorder except that mania
is absent in bipolar II disorder, and hypomania (a milder form of
mania) is the essential diagnostic finding.
EPIDEMIOLOGY
The lifetime prevalence of bipolar II disorder is about 0.5%.
Bipolar II disorder may be more common in women.
ETIOLOGY
Current evidence implicates the same factors as for bipolar I
disorder.

Bipolar II disorder is characterized by the occurrence of hypomania
and major depressive episodes in an individual who has never met
criteria for a manic episode. Hypomania is determined by the same
symptom complex as mania, but the symptoms are less severe,
cause less impairment, and do not require hospitalization. Bipolar
II disorder is cyclic; the course of untreated bipolar II disorder is
presented in Figure 2-1B. Suicide occurs in 10% to 15% of
patients.
The differential diagnosis for bipolar II disorder is the same as for
bipolar I disorder.
MANAGEMENT
The treatment is the same as for bipolar I disorder, although
hypomanic episodes typically do not require as aggressive a
treatment regimen as do manic episodes. Care must be taken in
prescribing antidepressants for major depressive episodes or
depressive episodes because of their potential role in prompting
more severe or frequent hypomanic episodes.
CYCLOTHYMIC DISORDER
Cyclothymic disorder is a recurrent, chronic, mild form of bipolar
disorder in which individuals experience numerous periods with
hypomanic symptoms that do not meet criteria for a hypomanic
episode and numerous periods with depressive symptoms that do
not meet criteria for a major depressive episode. It is not diagnosed
if a person has experienced either a manic, hypomanic, or major
depressive episode.
EPIDEMIOLOGY
The lifetime prevalence of cyclothymic disorder is 0.4% to 1%.
The rate appears equal in men and women, although women more
often seek treatment.
ETIOLOGY
Familial and genetic studies reveal an association with other mood
disorders.

Cyclothymic disorder is a milder form of bipolar disorder
consisting of recurrent mood disturbances with hypomanic
symptoms that do not meet criteria for a hypomanic episode and
depressive symptoms that do not meet criteria for a major
depressive episode. These symptoms must last at least 2 years and
the individual cannot go without symptoms for more than 2
months. Cyclothymic disorder is never diagnosed when there is a
history of a manic, major depressive, or mixed episode. The course
of untreated cyclothymic disorder is depicted in Figure 2-1C.
The principal differential diagnoses include other depressive and
bipolar disorders, substance-induced depressive or bipolar
disorders, and depressive, bipolar, or related disorders due to
another medical condition. Personality disorders (especially
borderline personality disorder) with labile mood may be confused
with cyclothymic disorder.
MANAGEMENT
Psychotherapy, mood stabilizers, and antidepressants are used.
Individuals with cyclothymic disorder, however, may never seek
medical attention for their mood symptoms.
SUBSTANCE-INDUCED BIPOLAR
DISORDERS
Substance-induced bipolar disorder is diagnosed when medications,
other psychoactive substances, ECT, or phototherapy are proximate
events and the likely cause of the mood disturbance and when the
mood disturbance does not extend beyond the expected effects of
the causative agent.
BIPOLAR DISORDER DUE TO ANOTHER

MEDICAL CONDITION
This category is for bipolar disorders caused by a medical illness.
Endocrine disorders, such as thyroid and adrenal dysfunction, are
common etiologies.
COMMON SPECIFIERS
The most common specifier is rapid cycling. Patients with bipolar
disorder may have frequent (rapid) cycles. To meet criteria for
rapid cycling, four mood disturbances per year must be present.
The suicide rate may be higher than in nonrapid cyclers.
KEY POINTS
Bipolar I disorder is a biphasic cyclic mood
disorder with a 10% to 15% suicide rate.
Bipolar I disorder requires maintenance treatment
with mood stabilizers or antipsychotics;
combination therapy is common.
Bipolar II disorder is a biphasic recurrent mood
disorder with hypomania; the suicide rate is 10%
to 15%.
Cyclothymic disorder is a chronic, recurrent
biphasic mood disorder without frank manic or
major depressive episodes.
CLINICAL VIGNETTES
VIGNETTE 1
A 64-year-old Caucasian woman with a long history of mental illness
presents to the emergency room (ER) with her daughter. The
daughter reports that her mother has not been taking her prescribed
medications since she had a colonoscopy last month. She thought she
had to stop the medicines for the procedure and then never restarted
them. The patient has been suffering with mental illness since she had
a manic and psychotic episode 42 years ago while in college. Since
then she has had many episodes—some depressive episodes, some
manic, and some mixed. Most of the time she also has delusions and
hallucinations, even during long periods when her mood is euthymic.
On her most recent medication regimen, she had been stable for 3
years before stopping medications for the colonoscopy. She drank
alcohol with some severe consequences in her 30s and 40s but has
been sober for 18 years. She uses no other drugs. Currently, she is
hyperverbal, silly, and grandiose. She is flirtatious with a nurse in the
ER and easily distracted. The daughter says she is not sleeping and
has been up working on a writing project. You wonder if she has
bipolar disorder or schizoaffective disorder and begin to ask more
systematic questions.
1. What is the most important history that you need in order to make
the diagnosis?
a. The frequency of the mood episodes
b. The severity of the manic episodes
c. The presence of psychosis during a depressive episode
d. The absence of a mood episode during a psychotic episode
e. The absence of a psychosis during a mood episode
2. Factors that will determine her need for hospitalization include all
the following EXCEPT:
a. The patient’s ability to care for herself
b. The daughter’s request to take the patient home
c. The patients level of suicidal risk
d. The patient’s level of homicidal risk
3. The next most reasonable step would be to:

a. Determine which medications she had previously taken and
develop a plan to safely resume them.
b. Admit the patient for observation and try her on a new
experimental therapy.
c. Discharge the patient and instruct her to call her psychiatrist in
the morning.
d. Immediately inject the patient with a long-acting antipsychotic
due to her nonadherence.
e. Start electroconvulsive therapy (ECT) because her medications
have not kept her stable.
VIGNETTE 2
A 33-year-old woman presents to the office to establish care with a
psychiatrist after she was referred by her primary care provider
because of some unusual behavior. The patient reports a history of
two prior episodes of major depression that were treated with setraline
for a few months and that remitted. Her last depressive episode was 2
years ago. Her current symptoms started about 1 month ago. Most
days for the past month, she describes feeling very energized and
subsequently requiring only 3 or 4 hours of sleep nightly when her
usual required amount was at least 8 hours. Despite that, she
continues to function at work and is recently making more sales in her
work at a clothing store than ever before. Her coworkers noticed that
she was talking faster than usual and appears to get side-tracked
easily when she was previously able to stay on task. She was
concerned about her spending because she paid $2,500 for new
outfits during the past 2 weeks and was reprimanded by her financial
advisor after having worked very hard to maintain a strict budget to
save money for tuition to return to school. Despite all of the above,
she is still able to have a conversation and did not feel it was
necessary to go to the emergency department given these recent
changes. She had been up late for several nights before all this as she
was busy filling out graduate school applications with a tight deadline.
She has had a tubal ligation.
1. What is the most likely diagnosis at the time of this visit?

a. Bipolar I disorder
b. Major depressive disorder
c. Cyclothymic disorder
d. Bipolar II disorder
e. Persistent depressive disorder
2. What is the most likely useful regimen?

a. Lithium monotherapy
b. ECT
c. Serotonin receptor inhibitor
d. Serotonin–norepinephrine receptor inhibitor
e. No treatment is necessary
ANSWERS
VIGNETTE 1 Question 1
1. Answer D:
The absence of a mood episode during a psychotic episode of at least
2 weeks’ duration in a patient who also has a history of mania or
mixed episodes is required to make the diagnosis of schizoaffective
disorder. Although the frequency and severity of mood episodes is
relevant to the history, it does not help to differentiate bipolar from
schizoaffective disorders but may be useful in diagnosing the rapid
cycling subtype of bipolar I disorder if there are at least four mood
disturbances per year. The suicide rate may be higher in the rapid
cycling subtype of bipolar disorder than in patients who do not have
rapid cycling. Similarly, the presence of psychosis during a depressive
episode or the absence of psychosis during a mood episode can
occur in either bipolar disorder or schizoaffective disorder.
2. Answer B:
The daughter’s request to take the patient home is important to the
patient’s recovery but is not a determining factor that can be used to
decide the patient’s medical necessity for inpatient care. If the patient
is unable to care for herself to point where she is in imminent danger
or if her level of suicidal or homicidal ideation is of sufficient concern
and she cannot agree to maintain safety outside a hospital
environment, the general criteria for inpatient admission have been
met. Once the patient is considered ready for discharge, her
daughter’s level of support and ability to reduce risk (e.g., monitoring
medications or removing weapons from the home) may play an
important role in the discharge planning.
3. Answer A:
The next best step is to determine which medications she had
previously taken and make a plan to resume them in a safe manner.
While this might involve a hospitalization, it could also be done with
outpatient support if there are not safety concerns warranting an
inpatient admission. A new, untried therapy is not called for in a
patient who was previously stable on her usual medications.
Releasing the patient and instructing her to call her psychiatrist falls
short of the standard of care because the patient has been brought in
with acute symptoms while off of previously effective medications and
should have a treatment plan initiated immediately. Choosing to give a
patient a long-acting, injectable antipsychotic is a long-term decision
that should only be pursued if there is a plan to follow the patient over
time and in consultation with her current treating psychiatrist and after
assessing the patient’s response to an oral form of the medication.
There is not enough evidence currently to indicate that the patient
needs ECT as she has responded well to medications in the past.
1. Answer D:
Bipolar II disorder is characterized by the occurrence of hypomania
and major depressive episodes in an individual who has never met
criteria for a manic episode. The patient is displaying symptoms
consistent with hypomania. Hypomania is determined by the same
symptom complex as mania (a change in mood that is different from
one’s baseline or usual mood and increased energy and activity), but
the symptoms are less severe, cause less impairment, and do not
require hospitalization. She has never experienced a manic episode,
and thus she cannot currently be diagnosed with bipolar I disorder.
She has experienced major depressive episodes although she is not
currently depressed. Thus, she cannot be diagnosed with major
depressive disorder or persistent depressive disorder at this point.
Similarly, since she has had both prior major depression and current
hypomania, she does not meet criteria for cyclothymia, which would
require a 2-year period of hypomanic and depressive symptoms not
meeting criteria for major depression or hypomania. If the patient
subsequently experiences an episode consistent with mania, the
diagnosis would be revised to bipolar I disorder.
2. Answer A:
Based on randomized trials, drug classes commonly used to treat
acute mania or hypomania include lithium, some anticonvulsants with
mood-stabilizing properties, antipsychotics, and benzodiazepines.
ECT would not be warranted in the case of hypomania but is useful for
severe or refractory mania. Although she has previously been treated
successfully with sertraline without evidence provided for the induction
of hypomania, serotonin reuptake inhibitors and serotonin–
norepinephrine reuptake inhibitors would potentially exacerbate
hypomania because they are antidepressants and can increase or
induce mania in susceptible individuals. This patient’s condition is
causing her significant distress, and thus treatment would be
warranted. Lithium is an excellent first choice because of its well-
established efficacy and safety when used within appropriate dosing
parameters. Although this patient does not present with suicidal
thinking and no history of prior suicidal ideation or attempts is
provided, lithium use has also been associated with marked
reductions in suicide attempts and completed suicide. However, it is
critical to note that in individuals maintained for lithium for a sustained
period of time for mood disorders, abrupt cessation of lithium can
greatly increase suicide risk for up to 1 year after discontinuation.
Slow taper of lithium is therefore in order whenever possible if it needs
to be discontinued. Slow taper of lithium is associated with loss of
protective effects against suicide but does not appear to confer
increased risk above the baseline associated with mood disorders.
Mood disorders are among the most common diagnoses in
psychiatry. Mood is a persistent emotional state (as differentiated
from affect, which is the external display of feelings). The
Diagnostic and Statistical Manual of Mental Disorders, Fifth
edition (DSM-5) separated the classification of mood disorders into
depressive disorders and bipolar and related disorders. There are
five major categories of depressive disorders according to the
DSM-5: major depressive disorder, persistent depressive disorder
(dysthymia), premenstrual dysphoric disorder, disruptive mood
dysregulation disorder (DMDD), and depressive disorders having a
known etiology (substance/medication-induced depressive disorder
and depressive disorder caused by a general medical condition)
(Table 3-1).
TABLE 3-1. Depressive Disorders

Depressive Disorders
Major depressive disorder
Persistent depressive disorder (dysthymia)
Disruptive mood dysregulation disorder
Premenstrual dysphoric disorder
Substance/medication-induced depressive disorder
Depressive disorder due to another medical condition
NEURAL BASIS
The neural basis of depressive disorders is slowly emerging (Fig. 3-
1). It is now clear that, in addition to altered function in the
hypothalamic-pituitary-adrenal (HPA) axis and in multiple
neurotransmitter systems, some depressive disorders are also
associated with structural and functional brain alterations. Major
depression is the best studied among the depressive disorders. It is
now clear that major depression is a disorder affecting multiple
organ systems in addition to the brain, and that it is associated with
increased risk of dementia and cardiovascular disease, and likely
increased mortality in cancer patients. Although the neural basis of
depression is not fully understood, the condition is associated with
alterations in monoamine neurotransmitters (serotonin,
norepinephine, dopamine); alterations in glutamate
neurotransmission; reduced brain-derived neurotrophic factor and
reduced neuronal plasticity; functional and structural changes in
multiple brain regions, including frontal cortex (dorsolateral and
medial prefrontal cortex, anterior cingulate gyrus [especially
subgenual portion], and orbitofrontal cortex), the amygdala, the
hippocampus, the nucleus accumbens (a region critical in reward
processing and drug reinforcement); and altered cortisol secretion
via the HPA axis.
FIGURE 3-1. Brain regions showing structural and functional alteration
include frontal cortex (dorsolateral and medial prefrontal cortex,
anterior cingulate gyrus, and orbitofrontal cortex), the amygdala, the
hippocampus, the nucleus accumbens (a region critical in reward
processing and drug reinforcement), and the hypothalamic-pituitary-
adrenal axis (HPA) axis. (From Higgins ES, George MS.
Neuroscience of Clinical Psychiatry, 3rd ed. Philadelphia, PA: Wolters
Kluwer, 2019.)
MAJOR DEPRESSIVE DISORDER

Major depressive disorder is diagnosed after a single episode of
major depression (Table 3-2). It is characterized by emotional
changes, primarily depressed mood or lack of interest and pleasure,
and by vegetative changes, consisting of alterations in sleep,
appetite, and energy levels. A major depressive episode can occur
at any time from early childhood to old age. DSM-5 criteria for the
diagnosis of major depression require the presence of depressed
mood or decreased interest or pleasure, with a total of five
symptoms from the list in Table 3-2 that persist for at least 2
weeks.
Mood changes consist of depressed mood most of the day,

nearly every day in adults, but mood can be irritable in the child
and adolescent population. Sleep changes can consist of increased
sleep (hypersomnia, more common with atypical depression) or
insomnia. Middle insomnia is common, as are early morning
awakenings (especially in melancholic depression). Changes in
interest and pleasure include decreased interest and pleasure in
most activities for most of the day, nearly every day. Symptoms of
increased guilt can include guilty feelings or a sense of feeling
worthless. Changes in energy can consist of fatigue, tiredness, or
low energy.
Concentration and thinking may be markedly decreased and
decision making may be compromised by indecisiveness. There
may be changes in appetite with either increased appetite and
weight gain (more common in atypical depression) or decreased
appetite and weight loss.
Motor activity may be diminished (more common in atypical
depression) or there may be an increase in psychomotor activity.
Suicidal thinking may increase along a continuum, with milder
manifestations consisting of self-neglect or apathy about being
alive or more severely with active suicidal planning, suicide
attempt, or suicide.
EPIDEMIOLOGY
The lifetime prevalence (will occur at some point in a person’s life)
rate for major depressive disorder is around 16%. The female-to-
male ratio is 2:1. Race distributions appear equal, and
socioeconomic variables do not seem to be a factor. The incidence
(rate of new cases) is greatest in one’s 20s and decreases after the
age of 65. The 12-month prevalence for major depression is about
2.7% of children and about 13% in adolescents in the United
States; depression affects 5% of elderly persons.
ETIOLOGY
Psychological theories of depression generally view interpersonal
losses (actual or perceived) as risk factors for developing
depression. In fact, available evidence suggests that childhood loss
of a parent or loss of a spouse is associated with depression, as are
other adverse childhood events. Classic psychoanalytic theories
center on ambivalence toward the lost object (person), although
more recent theories focus on the critical importance of the object
relationship in maintaining psychic equilibrium and self-regard.
The cognitive-behavioral model views cognitive distortions as the
primary events that foster a negative misperception of the world,
which in turn generate negative emotions. The learned helplessness
model (based on animal studies) suggests that depression arises
when individuals come to believe they have no control over the
stresses and pains that beset them.
Biologic, familial, and genetic data support the idea of a
biologic diathesis in the genesis of depression. Genetic studies
show that depression is found to be concordant more often in
monozygotic twins than in dizygotic twins. Unipolar depression in
a parent leads to an increased incidence of both unipolar and
bipolar mood disorders in their offspring.
Sleep disturbances are nearly universal complaints in those who
are depressed. Objective evidence from sleep studies reveals that
deep sleep (delta sleep, stages 3 and 4) is decreased in depression
and that rapid eye movement (REM) sleep alterations include
increased time spent in REM and earlier onset of REM in the sleep
cycle (decreased latency to REM). It is unclear whether sleep
alterations cause depression or are a manifestation of the illness.

A major depressive disorder is diagnosed if a patient experiences at
least one episode of major depression and does not meet criteria for
bipolar disorder or etiologic mood disorder. Major depression is
characterized by emotional and vegetative changes. Emotional
changes most commonly include depressed mood with feelings of
sadness, hopelessness, guilt, and despair. Irritability may be the
primary mood complaint in children and adolescents. Vegetative
symptoms include alterations in sleep, appetite, energy, and libido.
In addition to the symptoms seen in adults, children present with
school avoidance, problems with authority, frequent headaches or
stomachaches, and anger outbursts. Elderly persons, often beset by
grief, loss, or medical illness, present with the usual adult
symptoms and with higher rates of co-occurring anxiety.
Major depression is frequently recurrent. The usual duration
of an untreated episode (Fig. 3-2A) is 6 to 12 months. Of patients
diagnosed with major depression, 15% die by suicide at some point
in their lifetime.
FIGURE 3-2. Unipolar mood disorders. (A) Major depressive disorder.

(B) Dysthymic disorder.
Mood disorders secondary to (induced by) medical illnesses or
substance abuse are the primary differential diagnoses. Psychotic
depression must be differentiated from schizophrenia; negative
symptoms of schizophrenia can mimic depression. Persons with
major depression may eventually meet criteria for bipolar disorder.
MANAGEMENT
Depression is responsive to psychotherapy and
pharmacotherapy. Milder cases may be treated with brief
psychotherapy interventions alone. For more severe cases,
antidepressant medications combined with psychotherapy are
superior to medications or psychotherapy alone. Among the
psychotherapies, supportive, cognitive-behavioral, and brief
interpersonal therapies have the most data to support their efficacy.
There are many classes of antidepressants available that are
effective and are usually chosen according to side-effect profiles.
At present, available classes of antidepressants include tricyclic
antidepressants, selective serotonin reuptake inhibitors (SSRIs),
monoamine oxidase inhibitors, and atypical antidepressants. In
addition, lithium, thyroid hormone, atypical antipsychotics, and
psychostimulants may be used as augmentative treatments.
Children and adolescents with depression benefit from some
antidepressants and from psychotherapy as well. They may be at
higher risk of suicide during active pharmacologic treatment, and
sufferers should be carefully followed up by a mental health
specialist. Elderly persons with depression do best when low
dosages of antidepressants are initiated and these are increased
slowly in conjunction with psychotherapy.
Electroconvulsive therapy (ECT) is used in psychotic, severe or
treatment-refractory depressions, or when medications are
contraindicated (e.g., in elderly or debilitated individuals). Vagal
nerve stimulation, a novel bioelectrical treatment involving the
electrical stimulation of the vagus nerve via a surgically implanted
device has shown some promise as a potential treatment for major
depression. Transcranial magnetic stimulation is approved for
treating depression and is becomingly increasingly common.
Antipsychotic medications are an essential adjunct to
antidepressants in psychotic depressions and may be helpful even
in nonpsychotic depression. Anxiolytics may be used as adjuncts to
antidepressants in depression with high levels of anxiety, although
moresedating antidepressants may suffice. Phototherapy can be
used for seasonal mood disorders and has efficacy for nonseasonal
depression as well.
PERSISTENT DEPRESSIVE DISORDER

(DYSTHYMIA)
Persistent depressive disorder is a milder, chronic form of major
depression.
EPIDEMIOLOGY
The lifetime prevalence is 6%.
ETIOLOGY
Because persistent depressive disorder is often conceptualized as a
milder, chronic form of major depression, similar etiologies are
generally attributed to persistent depressive disorder.

Persistent depressive disorder is a chronic and less severe form of
major depression. The diagnosis of persistent depressive disorder
requires that an individual experience a minimum of 2 years of
chronically depressed mood most of the time (Fig. 3-2B).
Associated symptoms and complaints may include change in
appetite and sleep, fatigue, decreased concentration, and
hopelessness. Persistent depressive disorder can be chronic and
difficult to treat. At times, major depressive episodes may co-
occur, giving rise to the term double depression.
Major depression and etiologic mood disorders are the primary
differential diagnostic considerations.
MANAGEMENT
Treatment is similar to that for major depression, except that
psychotherapy may play a larger role, and the course of treatment
may be more protracted.
DISRUPTIVE MOOD DYSREGULATION

DISORDER
EPIDEMIOLOGY
DMDD is more common in males and has an estimated 2% to 5%
1-year prevalence rate. The condition appears to be more strongly
associated with risk for future depression than bipolar disorder.
ETIOLOGY
The etiology of this condition is unknown.
The hallmark clinical manifestation of DMDD is chronic, severe
irritability with frequent severe temper outbursts that impair
functioning across a variety of environments. The temper outbursts
have to average 3 or more per week and should occur regularly
over a 1-year period (with no period longer than 3 months without
an outburst). The diagnosis is permitted for children 6 to 18 years
old.
History and Mental Status Examinations

The history will reveal frequent periods of sustained irritability
with intermittent temper outbursts that are either verbal or physical
and that are targeted against people or property. The mental status
examination might reveal an irritable affect with self-report of bad
or irritable mood. Symptoms suggestive of mania, that is, pressured
speech, grandiosity, and flight of ideas should be absent.
DMDD should be differentiated from attention deficit hyperactivity
disorder (ADHD) and oppositional defiant disorder. Bipolar
disorder may be associated with irritability, but mood changes in
bipolar disorder are episodic while irritability is a constant feature
of DMDD. In intermittent explosive disorder, anger and aggression
are the prominent features.
MANAGEMENT
There is no specific management yet approved for DMDD.
Treatments that have shown efficacy for symptoms of the disorder
include psychotherapy, positive parenting, psychostimulants,
valproic acid, antidepressants, and atypical antipsychotics.
PREMENSTRUAL DYSPHORIC DISORDER

Premenstrual dysphoric disorder is diagnosed when recurrent mood
and behavior symptoms occur repeatedly in association with a
woman’s menstrual cycle.
EPIDEMIOLOGY
Premenstrual dysphoric disorder has a 1-year prevalence of about
2% to 8%. Onset can occur anytime after a woman starts
menstruating, and the condition subsides with menopause.
ETIOLOGY
This condition is presumed to be caused by hormonal changes
associated with the menstrual cycle.
Symptoms of this condition should be present for most menstrual
cycles and occur in the week preceding menses and begin
improving after menstruation. DSM-5 criteria require that at least
one of the following symptoms should be present: (1) unstable
affect, (2) irritability/anger, (3) mood changes (depressed or
hopeless), and (4) anxiety/tension. At least one of the following
must also be present: (1) decreased interests, (2) decreased
concentration, (3) fatigue/low energy, (4) appetite increase or
decrease, (5) sleep increase or decrease, (6) feeling overwhelmed,
and (7) somatic symptoms (breast tenderness, musculoskeletal
pain, bloating). To meet diagnostic criteria, a total of five
symptoms should be present.
History and Mental Status Examinations

Women with this condition will report recurrent mood and somatic
symptoms in association with their menstrual cycle. Mental status
during the symptomatic period of premenstrual dysphoric disorder
might reveal depressed or irritable mood, and sad, irritable, or
anxious affect.
This condition should be differentiated from other gynecologic
conditions, depressive conditions, bipolar disorder, and response to
hormone therapy.
MANAGEMENT
Management of this condition has not been sufficiently studied.
Antidepressants of the SSRI class and hormonal therapy are the
primary treatments.
MOOD DISORDERS WITH KNOWN ETIOLOGY
SUBSTANCE/MEDICATION-INDUCED DEPRESSIVE
DISORDER
Substance-induced mood disorder is diagnosed when medications,
other psychoactive substances, ECT, or phototherapy are proximate
events and the likely cause of the mood disturbance. All the
aforementioned types of mood disorder (e.g., unipolar, bipolar)
may occur.
DEPRESSIVE DISORDER RESULTING FROM A

GENERAL MEDICAL CONDITION
This category is for depression apparently caused by a medical
illness. Endocrine disorders, such as thyroid and adrenal
dysfunction, are common etiologies. Peripartum mood disorders
are excluded from this diagnosis.
SUBTYPES AND MODIFIERS

Various diagnostic specifiers can be applied to specific subtypes of
depressive disorders. These have prognostic and treatment
implications and may prove to have etiologic implications.
With Anxious Distress: This specifier is used when there are
marked anxiety symptoms.
With Mixed Features: When symptoms of mania or hypomania
are also present.
Melancholic: Melancholic depression is a severe form of
depression associated with guilt, remorse, loss of pleasure, and
extreme vegetative symptoms.
Peripartum: Peripartum depression occurs before delivery or
within 4 weeks of childbirth. The presence of one episode of
peripartum mood disorder is strongly predictive of a recurrence.
Seasonal: Seasonal depressive disorders show a consistent
seasonal pattern of variation. The most common pattern is a
worsening of depression during the fall and winter with
improvement in the spring.
Atypical: Atypical depressions show a pattern of hypersomnia,
increased appetite or weight gain, mood reactivity, long-standing
rejection sensitivity, anergia, and leaden paralysis.
Psychotic: This specifier is used when psychotic symptoms are
present during a depressive episode.
Catatonic: The catatonic specifier is applied to depressive
disorders when catatonia is present (see Chapter 1).
KEY POINTS
Major depression is a recurrent mood disorder
with a 15% suicide rate.
Combined psychotherapy and pharmacotherapy is
the best treatment for major depression.
Persistent depressive disorder (dysthymia) is a
chronic mood disorder (lasting at least 2 years).
Persistent depressive disorder (dysthymia) is often
refractory to treatment.
CLINICAL VIGNETTES
VIGNETTE 1
A 45-year-old man presents to the office after he had to shut down his
business of 15 years in the context of a significant economic crisis.
After that happened 1 month ago, he has been unable to get out of
bed in the morning and feels unmotivated. His mood has been
depressed most of the day, nearly every day, and family members
have noticed him being more subdued and slow in his speech and
movement. He no longer goes out to play tennis and states that he
has lost interest in gardening, once a favorite hobby. He feels tired
often and has been skipping meals because he rarely feels hungry.
He blames himself for letting his employees go and feels like he failed
them. He has been waking up at 4 am every morning and having
difficulty returning to sleep. Despite that, he remains hopeful that
things will turn around and that he will find another work opportunity to
get him going. Although he has felt like giving up and has transient
thoughts that it would be easier to be dead, he reports that his faith
keeps him strong and deters him from contemplating suicide. He has
never attempted to end his life in the past or to hurt himself
intentionally. He reports no history of mania or psychosis.
1. What is the most likely diagnosis at this time?

a. Bipolar I disorder
d. Bipolar II disorder
e. Persistent depressive disorder
2. The patient is started on first-line treatment for this condition and

the dose is optimized; however, his symptoms get worse after the
unexpected death of his mother few days before the next visit. He
states that “if she is no longer here, then I might as well not be
here anymore.” He reports no suicidal plan, no suicidal intent, and
no access to weapons. Nevertheless, you are concerned about
his suicidality. You decide to augment his treatment with another
agent. Which one would you choose?
a. Benzodiazepine
b. Lithium
c. Valproic acid
d. Gabapentin
e. Carbamazepine
VIGNETTE 2
You are an outpatient psychiatrist practicing at the student health
center of a small college campus. A 24-year-old female student
presents to your office complaining of the recent onset of low mood
and poor concentration, precipitated by increasing difficulty in
managing her college courses. Her symptoms started about 3 weeks
before her presentation to student health. After completing a history
and physical and ordering and reviewing appropriate laboratory work,
you diagnose her with major depressive disorder, single episode, mild.
The patient indicates that she would prefer to avoid treatment with
medications if at all possible.
1. In determining the treatment plan for a patient who prefers to

avoid medications, psychotherapy is a first-line treatment option.
Which of the following psychotherapeutic modalities has the
greatest evidence base in the treatment of major depression?
a. Cognitive-behavioral therapy (CBT)
b. Dialectical behavioral therapy (DBT)
c. Exposure therapy
d. Family therapy
e. Long-term psychodynamic psychotherapy
2. The patient is referred to a CBT therapist but cannot find a CBT

therapist who accepts her insurance. She contacts you for a
follow-up appointment. In the meantime, her depression has
worsened and she now has marked neurovegetative symptoms
and some intermittent suicidal thoughts with no plan or intent to
harm herself. She is now interested in starting medications. After
a careful review of the risks and benefits of medications, you
suggest that she begin a trial of:
a. Lithium
b. Sertraline
c. Lamotrigine
d. Aripiprazole
e. Armodafinil
3. The patient returns to your office 1 month after starting treatment

with sertraline. Her mood and her energy are greatly improved.
She states she has cleaned her house several times and is only
sleeping 2 to 3 hours each night. She is speaking quickly and
appears distractible. The most appropriate treatment would be:
a. Increase her sertraline
b. Schedule electroconvulsive therapy (ECT)
c. Begin a mood stabilizer and stop sertraline
d. Begin DBT
e. Begin CBT
VIGNETTE 3
A 72-year-old white man presents to the emergency ward after his
daughter found him sitting on his bed with a loaded pistol in his hand.
The patient denies depression or suicidal thinking and states that he
was planning to clean the gun and that he keeps the gun for prowlers.
The patient’s daughter reports that he has seemed despondent since
his wife died a few months ago. He has lost a great deal of weight and
has not been sleeping or grooming himself well. He has not been
attending to his chores and is reluctant to socialize with others.
1. The most important initial management for this patient would

include:
a. A nutritional consult
b. Psychiatric hospitalization
c. Outpatient psychotherapy referral
d. Outpatient psychopharmacology referral
e. Neurologic consultation
2. Components of the patient’s history indicate that he is at

increased risk for suicide. The first is major depression. The
others are:
a. Weight loss
b. Failure to do chores
c. Hopelessness
d. Age, race, gender, and lack of sleep
e. Poor grooming
3. Once hospitalized in a secure setting, appropriate treatment for

this patient includes:
a. Buspirone
b. Dialectical behavioral psychotherapy
c. Propanolol
d. Mirtazapine
e. Valproic acid
4. The patient is admitted to the hospital, and treatment is initiated

with mirtazapine; however, he continues to worsen and is unable
to eat or drink. He develops hopelessness and continually
ruminates about his life. He is now actively suicidal and freely
admits a desire to die. He has severe psychomotor retardation
and has little spontaneous speech. A reasonable next step in
treating this patient is:
a. Decrease the mirtazapine
b. Evaluate the patient for ECT
c. CBT
d. Multivitamins
e. Add gabapentin
ANSWERS
1. Answer B:
The patient is displaying classic neurovegetative symptoms and signs
of major depression with no history of mania or psychosis. Major
depression is diagnosed in the presence of emotional changes,
primarily depressed mood or lack of interest and pleasure, and by
vegetative changes, consisting of alterations in sleep, appetite, and
energy levels that persist for at least 2 weeks and that cause
significant distress or impairment. The patient’s symptoms have been
present for 1 month, and thus a diagnosis of persistent depressive
disorder (dysthymia) is not warranted because the duration criteria for
this condition are at least 2 years. There are no elements of mania or
hypomania in the history, and hence bipolar and cyclothymic disorders
could not be diagnosed at this time. The patient could develop mania
or hypomania at a later date at which point the diagnosis would be
revised.
2. Answer B:
Lithium, thyroid hormone, some atypical antipsychotics, and
stimulants may be used for augmentation of antidepressant therapy in
major depression. Among these, lithium has demonstrated the most
efficacy in reducing suicidal ideation. However, it is critical to note that
in individuals maintained for lithium for a sustained period of time for
mood disorders, abrupt cessation of lithium can greatly increase
suicide risk for up to 1 year after discontinuation. Slow taper of lithium
is therefore in order whenever possible if it needs to be discontinued.
Slow taper of lithium is associated with loss of protective effects
against suicide but does not appear to confer increased risk above the
baseline associated with mood disorders. Because of the increased
risk for developing a benzodiazepine use disorder in susceptible
patients, benzodiazepines are used increasingly less often in
psychiatry except for acute conditions. Valproic acid and
carbamazepine have mood-stabilizing properties and demonstrated
efficacy for bipolar disorder and are therefore reasonable medication
choices for an individual with bipolar disorder. However, they have not
demonstrated strong efficacy in treating major depression.
1. Answer A:
CBT was originally developed as a psychotherapeutic treatment
modality for mild-to-moderate depression, and there is significant
evidence of its efficacy in both treatment and prevention of relapse in
this context. It has also subsequently gained strong empirical
validation for the treatment of social phobia, panic disorder,
obsessive-compulsive disorder, and posttraumatic stress disorder.
CBT involves identifying and gently challenging distorted core beliefs
and the use of behavioral techniques to produce change in mood and
behavior. Interpersonal psychotherapy, which focuses on improving
the patient’s interactions with others, also has significant empirical
support in the treatment of depression. DBT incorporates CBT and
Eastern Zen philosophy and is the psychotherapeutic modality of
choice for treatment of borderline personality disorder. Exposure
therapy is used in the treatment of specific phobias. Family therapy
focuses on interactions between family members to improve
functioning of the family unit as a whole and is of particular benefit in
child psychiatry. Long-term psychodynamic therapy seeks to improve
understanding of one’s psyche including unconscious conflicts and
defense mechanisms to bring about improved self-realization and
change.
2. Answer B:
Of the listed medication options, the selective serotonin reuptake
inhibitor (SSRI) sertraline is a first-line choice for treating major
depression. SSRIs are well tolerated and efficacious. Lithium is used
in bipolar disorder and bipolar depression and is also used to augment
antidepressants in major depression but would not be indicated at
present in a patient who does not have a history suggestive of mania
or inadequate response to sertraline. Lamotrigine is an anticonvulsant
that is used in the treatment of bipolar depression. Aripiprazole is an
atypical antipsychotic that is used to augment the antidepressant
response to SSRIs if augmentation is needed. Armodafinil is a wake-
promoting agent that may have use as an adjunct in some forms of
depression when characterized by excessive sleepiness or
psychomotor slowing but is not indicated as first-line treatment for
depression.
3. Answer C:
The patient has likely developed substance-induced mania caused by
sertraline treatment for her major depression. The most appropriate
treatment would be to stop sertraline and begin a mood stabilizer such
as lithium or valproate. ECT can be used for both depression and
mania but only in severe cases that are refractory to other treatment.
DBT is indicated for borderline personality disorder. CBT examines
cognitive distortions and is primarily useful for depression and anxiety
disorders but this patient has been unable to find a provider for CBT
treatment.
1. Answer B:
This patient appears to have major depression likely brought on by his
wife’s death. That his daughter has observed the patient to be
despondent, the lack of sleep and grooming, and the apparent weight
loss, is suggestive of major depression. A person can have
bereavement following the loss of a loved one, but these symptoms
are more severe and therefore consistent with major depression.
Because the patient was found with a gun, has severe symptoms, and
is denying illness, it is more appropriate to admit the patient to a
psychiatric hospital than to arrange for outpatient treatment.
Neurologic consultation and nutritional therapy may be important
components of this patient’s management once he has been placed in
a safe setting.
2. Answer D:
The suicide rate in Caucasian men over age 65 is five times that of the
general population. Insomnia has been independently associated with
increasing suicide risk. Psychiatric disorders, especially major
depression, also increase the risk of suicide. Hopelessness about the
future increases the risk of suicide but the patient does not report
hopelessness in this case. Weight loss, poor grooming, and lack of
interest in usual activities such as chores are associated with major
depression but have not been shown to be strong indicators for
increased suicide risk.
3. Answer D:
Appropriate initial therapy for this patient would include an
antidepressant medication. Mirtazapine is often used in elderly
individuals and improves sleep and appetite. Buspirone is sometimes
used as an adjunct to antidepressant treatment but is approved for
treating generalized anxiety disorder. DBT has been demonstrated to
be effective mainly in the treatment of borderline personality disorder.
Propanolol is a β-blocker medication. While some evidence supports
the role of some β-blockers in accelerating SSRI response, β-blockers
do not appear to have a role as monotherapy in treating major
depression and may exacerbate or cause symptoms of depression.
Valproic acid is a mood-stabilizing medication most appropriate for
treating mania in bipolar disorder. This patient does not display
evidence of mania.
4. Answer B:
ECT is an appropriate treatment option in an elderly individual with
life-threatening depression. Decreasing the mirtazapine would not
improve, but might worsen this patient’s condition. CBT is a useful
treatment for mild-to-moderate depression but is not appropriate given
the severity of this patient’s symptoms (but might be an important
therapy once he improves somewhat). Multivitamins may be important
for general good health and may have a role in treating specific
vitamin deficiencies but do not treat depression per se. Gabapentin is
used for seizure disorders and neuropathic pain of some types but has
not been demonstrated clear efficacy in treating severe depression.
The term anxiety refers to many states in which the sufferer
experiences a sense of impending threat or doom that is not well
defined or realistically based. Anxiety can be adaptive or
pathologic, transient or chronic, and has a variety of psychological
and physical manifestations. Anxiety disorders are a
heterogeneous group of disorders in which the feeling of anxiety is
the major element. They are the most prevalent group of
psychiatric disorders. According to global studies, 33% of all
human beings experience an anxiety disorder sometime in their
lifetime; approximately 18% of Americans meet the Diagnostic
and Statistical Manual of Mental Disorders, Fifth edition (DSM-5)
criteria at a given point in time (so-called point prevalence).
Accepted criteria for the diagnosis of anxiety disorders are shown
in Table 4-1. Approximately 50% of patients with anxiety disorders
also have suffered from a mood disorder, most commonly major
depression. Generally, anxiety disorders have an onset in the first
or second decade of life, peak in midlife, and decrease in frequency
with age. People with anxiety disorders are often also
disproportionately high utilizers of all types of health care, and
their lifetime care costs are higher than that those of the consumer
without anxiety. There is a strong genetic etiology and a clear
positive correlation between early life trauma and the expression of
anxiety disorders.
TABLE 4-1. Anxiety Disorders
Specific phobias
Social anxiety disorder
Panic disorder
Agoraphobia
Generalized anxiety disorder
Substance-induced anxiety disorder
Anxiety disorder due to another medical condition
Unspecified anxiety disorder
NEURAL BASIS
Anxiety disorders appear to be caused by an interaction of genetic,
psychological, and social factors that lead to clinically significant
syndromes.The genetic risk appears to co-occur with the risk of
other types of psychiatric disorders (depression and substance
dependence) and the phenotypic expression can be heightened by
life events and trauma. Anxiety disorders do not appear to have a
single shared neurobiologic basis, but rather a combination of
etiologies mediated by norepinephrine (from the locus coeruleus),
serotonin (from the raphe nuclei), γ-aminobutyric acid (GABA),
glutamate, dopamine, and peptide neurotransmitters (CCK-4 and
neuropeptide Y). Anxiety disorders have strong associations with
fear; and the amygdala, the brain region having a key role in
regulating the stress response, is thought to play a central role in
this regard (Fig. 4-1). Regions of the prefrontal cortex and
hippocampus are also important, serving as processing or
communicating structures in the manifestation of anxiety. Animal
models have focused on the brain response to novel stimuli because
it is believed that in anxiety disorders in humans there is an
abnormally fearful response to typical circumstances that the
anxious person perceives as abnormal or dangerous. The
expression of the symptomatology involves not only the mental
experience but also physiologic sensations (tachycardia,
diaphoresis, nausea) mediated by the autonomic nervous system.
FIGURE 4-1. The amygdala regulates the stress response. Incoming

sensory information is integrated in the basolateral nuclei of the
amygdala and relayed to the central nucleus of the amygdala. The
central nucleus activates a series of brain regions to drive the body’s
stress response. HPA, hypothalamic-pituitary-adrenal. (From Bear
MF, Connors BW, Paradiso MA. Neuroscience: Exploring the Brain,
PANIC DISORDER
Panic disorder is characterized by recurrent unexpected panic
attacks. The condition is severe enough to warrant diagnosis when
the attacks interfere with usual social and occupational functioning.
Table 4-2 outlines diagnostic criteria for a panic attack. It
commonly co-occurs with agoraphobia (described later), although
it is also seen with mood disorders and substance use disorders,
making the differential diagnosis complicated. The diagnosis of
panic disorder is made when preoccupation ensues and then
persists for greater than 1 month that the panic attack will occur
and the distress caused leads to maladaptive behaviors not better
explained by another psychiatric or other medical condition.
TABLE 4-2. Diagnostic Criteria for Panic Attacks

A discrete period of intense fear or discomfort, in which four (or more) of
the following symptoms developed abruptly and reached a peak within 10
minutes:
• Palpitations, pounding heart, or accelerated heart rate
• Sweating
• Trembling or shaking
• Sensations of shortness of breath or smothering
• Feeling of choking
• Chest pain or discomfort
• Nausea or abdominal distress
• Feeling dizzy, unsteady, lightheaded, or faint
• Derealization (feelings of unreality) or depersonalization (being detached
from oneself)
• Fear of losing control
• Fear that one is dying
• Paresthesias (tingling)
• Chills or hot flushes
EPIDEMIOLOGY
Panic disorder occurs more frequently in women, with a lifetime
prevalence of 2% to 3%. The typical onset is in the 20s, with most
cases beginning before age 30.
ETIOLOGY
The etiology of panic disorder is unknown. There are several
popular biologic theories involving brain stem carbon dioxide
hypersensitivity (the suffocation false alarm theory), abnormalities
in lactate metabolism, an abnormality of the locus coeruleus (the
region in the brain that regulates level of arousal), and elevated
central nervous system catecholamine levels. The GABA receptor
has also been implicated as etiologic because patients respond well
to benzodiazepines and because panic is induced in patients with
anxiety disorders using GABA antagonists.
Theorists posit that panic attacks are a conditioned response to
a fearful situation. For example, a person has an automobile
accident and experiences severe anxiety, including palpitations.
Thereafter, palpitations alone, experienced during exercise or any
sympathetic nervous system response, may induce the conditioned
response of a panic attack.

Panic disorder is characterized by recurrent, unexpected panic
attacks that can occur with or without agoraphobia (information to
follow). Panic attacks typically come on suddenly, peak within
minutes, and last 5 to 30 minutes. The patient must experience 4 of
the 13 typical symptoms of panic outlined in Table 4-2.
To warrant the diagnosis, one of the following must occur for at
least 1 month: persistent concern about having additional attacks,
worry about the implications of the attack (losing control, “going
crazy”), or a significant change of behavior related to the attacks
(e.g., restriction of activities).
Panic disorder is diagnosed after taking a thorough history and
performing necessary physical and laboratory examinations to rule
out medical causes. In particular, cardiac conditions, such as
rhythm disturbances, valvular abnormalities, and coronary artery
disease, need to be carefully excluded. The use of psychostimulants
such as cocaine or crystal methamphetamine must also be ruled
out.
Panic attacks should be distinguished from the direct physiologic
effects of a substance or a general medical condition (particularly
cardiac conditions or partial complex epilepsy). The panic attacks
also cannot be accounted for by another mental disorder, such as
social phobia or obsessive-compulsive disorder.
MANAGEMENT
The main treatments for panic disorder are pharmacotherapy and
cognitive-behavioral therapy (CBT) or their combination. Selective
serotonin reuptake inhibitors (SSRIs) are the first-line
pharmacologic therapy. Fluoxetine and sertraline have been studied
repeatedly and are options that are cost effective and well tolerated.
Other SSRIs such as escitalopram have shown effectiveness as
well. Selective norepinephrine reuptake inhibitors, tricyclic
antidepressants, monoamine oxidase inhibitors (MAOIs),
SSRIs, and benzodiazepines have been shown to be effective in
controlled studies. The risks of tolerance and dependence are high
with the use of benzodiazepines. Psychotherapy in the form of
CBT is the most well-studied intervention. It involves the use of
relaxation exercises and desensitization combined with education
aimed at helping patients understand that their panic attacks are, in
part, a result of misinterpreting internal (bodily) sensations.
Patients can then learn that the sensations are innocuous and self-
limited, which diminishes the panic response.
AGORAPHOBIA
Agoraphobia is a disabling condition in which patients fear places
from which escape might be difficult. Many patients with the
disorder become increasingly reclusive and ignore signs and
symptoms of psychiatric and other medical conditions to avoid
community situations and people. Panic disorder and agoraphobia
have traditionally been linked, but studies have shown that only
about one-third of patients with agoraphobia also have panic
disorder; most do not. Depression, substance abuse, and
undiagnosed medical conditions are much more common comorbid
conditions.

Agoraphobia is a disabling condition characterized by an intense
fear of places or situations in which escape might be difficult (or
embarrassing). Patients with agoraphobia and panic disorder
typically fear having a panic attack in a public place and being
embarrassed or unable to escape. Those with agoraphobia alone
(two-thirds of those with agoraphobia) simply avoid public arenas
but do not have panic attacks. Although some patients with
agoraphobia are so disabled that they are homebound, many are
comforted by the presence of a companion, allowing them to enter
some public places with less anxiety.
The condition is usually evident when taking a history, particularly
when the patient presents with family or caregivers who report the
avoidant and isolative behaviors. Keep in mind that most patients
with agoraphobia alone do not present for any kind of treatment.
Also, patients may underreport or minimize the symptoms, and
they may have developed an adaptation over many years of which
they are unaware. It is critical to take a comprehensive medical
history and screening, because many patients are fearful of being in
public and do not seek medical care. Obviously, one should be
sensitive to the patient’s fear of crowded or open spaces in
choosing setting and testing options. It is also common to find
other psychiatric conditions if one takes a careful history. Bouts of
depression, panic attacks, and overuse of prescription drugs or
alcohol are very common in patients who have agoraphobia.
EPIDEMIOLOGY
Agoraphobia also occurs more frequently in women, with a
lifetime prevalence of between 2% and 6%. Only one-third of
patients with agoraphobia also have panic disorder. However, most
patients with agoraphobia seen clinically also have panic disorder.
This apparent contradiction is because patients with agoraphobia
alone are unlikely to seek treatment.
ETIOLOGY
Agoraphobia is believed to arise from a conditioned restriction in
out-of-home activities due to recurrent emotionally traumatic
experiences such as feeling fearful in community settings. The
genetic risk for agoraphobia is believed to be that which
predisposes to other anxiety disorders. The underlying learned
behaviors seem to drive the chronicity of the disorder.
MANAGEMENT
Once a patient presents with agoraphobia, it is important to develop
an alliance with the patent to continue treatment. A patient
distressed by the condition is more likely to participate; if not,
family or caregiver alignment is critical. Use common sense to
design a treatment plan that accounts for the patient’s fear of being
in the community. Arranging for home-based care or a visiting
nurse is usually the first step. Exposure therapy, in which the
patient incrementally confronts a feared stimulus, has been shown
to be effective in treating agoraphobia. Medication plays a limited
role unless there are treatable co-occurring psychiatric or other
medical conditions.
SPECIFIC PHOBIA
Specific phobia is an anxiety disorder characterized by intense fear
of particular objects or situations (e.g., snakes, heights). It is the
most common psychiatric disorder. Accepted diagnostic criteria for
specific phobia are depicted in Table 4-3. The DSM-5 identifies
four category-specific subtypes of specific phobia and one general
category: (1) animal type, (2) natural environment type, (3) blood-
injection-injury type, (4) situational type, and (5) other type.
TABLE 4-3. Diagnostic Criteria for Specific Phobia

Fear Intense fear of particular objects or situations (e.g.,
snakes, heights)
Exposure Marked immediate anxiety on exposure to stimulus
nearly always
Disproportionate Fear is out of proportion to actual danger posed (unless
cultural)
Avoidance The feared stimulus is avoided or endured with much
anxiety/distress
Impairment Significantly impaired by the anxiety/distress or
avoidance
Duration Duration of at least 6 months
Exclusion The symptoms are not better accounted for by another
condition
EPIDEMIOLOGY
Specific phobias are more prevalent in women than in men and
occur with a lifetime prevalence of 25%. The typical onset is in
childhood, with most cases occurring before age 12.
ETIOLOGY
Phobic disorders, including specific phobia, tend to run in families.
Behavioral theorists argue that phobias are learned by being paired
with traumatic events.

A phobia is an irrational fear of a specific object, place, activity, or
situation that is out of proportion to any actual danger. To meet the
DSM-5 criteria for specific phobia, a patient must experience a
marked, persistent fear that is recognized by the patient to be
excessive or unreasonable and is cued by the presence or
anticipation of a specific object or situation. In addition, exposure
to the stimulus must almost invariably provoke the anxiety
reaction, and the avoidance of or distress over the feared situation
must impair everyday activities or relationships. For those younger
than age 18, symptoms must persist for at least 6 months.
The principal differential diagnosis is another mental disorder
(such as avoidance of school in separation anxiety disorder)
presenting with anxiety or fearfulness.
MANAGEMENT
Specific childhood phobias tend to remit spontaneously with age.
When they persist into adulthood, they often become chronic;
however, they rarely cause disability. Exposure therapy in the form
of systematic desensitization or flooding is the treatment of
choice. There is little role for medication.
SOCIAL ANXIETY DISORDER (SOCIAL

PHOBIA)
Social phobia (also known as social anxiety disorder [SAD]) is an
anxiety disorder in which patients have an intense fear of being
scrutinized in social or public situations (e.g., giving a speech,
speaking in class). The disorder may be generalized or limited to
performance situations. Accepted diagnostic criteria are outlined
in Table 4-4. The context criteria refer to circumstances in which
one might have a medical condition (e.g., psoriasis), but the social
anxiety is not related to what others think of the psoriasis but might
be a fear of voice cracking (e.g., in a singing performance). If
symptoms occur in most social situations, the social phobia is
specified as generalized social phobia.
TABLE 4-4. Diagnostic Criteria for Social Phobia (Social

Anxiety Disorder)
Fear Intense fear of a social or performance situation
involving exposure to strangers or perceived scrutiny
by others
Exposure Anxiety on exposure to the feared situation nearly
always
Disproportionate Fear is out of proportion to actual danger threat posed
(unless cultural)
Avoidance Avoidance of feared situation or endurance with much
distress
Impairment The anxiety/avoidance impairs functioning
Duration Duration of at least 6 months (in individuals younger
than age 18)
Exclusion The symptoms are not better explained by another
condition
Context When an actual medical condition is present, the
fear/anxiety is not related to the actual medical
condition
EPIDEMIOLOGY
Social phobias occur equally among men and women and affect
3% to 5% of the population. The typical onset is in adolescence,
with most cases occurring before age 25.
ETIOLOGY
Phobic disorders, including social phobia, tend to run in families.
Behavioral theorists argue that phobias are learned by being paired
with traumatic events. Some theorists posit that hypersensitivity to
rejection is a psychological antecedent of social phobia.

Social phobias are characterized by the fear of situations in which
the person is exposed to unfamiliar people or to possible scrutiny
by others. Exposure to the feared social situation must almost
invariably provoke an anxiety reaction. Avoidance of or distress
over the feared situation must impair everyday activities or
relationships. For those younger than age 18, symptoms must
persist for at least 6 months. Social phobia can either be
generalized (the patient fears nearly all situations) or limited to
specific situations.
The principal differential diagnosis is another mental disorder
(such as avoidance of school in separation anxiety disorder)
presenting with anxiety or fearfulness. However, other psychiatric
conditions that result in fear of others or misperception of oneself
relative to others should be considered. A person with major
depression might perceive harsh appraisal by others and would
therefore fear contact or scrutiny; similarly, a person with paranoid
delusions as part of schizophrenia would have irrational fears of
those perceived as dangerous.
MANAGEMENT
Mild cases of social phobia can be treated with CBT, but many
cases require medication. MAOIs, β-blockers, SSRIs, alprazolam,
and gabapentin have proved successful in treating social phobia.
SSRIs appear to be the most effective pharmacotherapy. CBT uses
the exposure therapy techniques of flooding and systematic
desensitization to reduce anxiety in feared situations. Supportive
individual and group psychotherapy is helpful to restore self-
esteem and to encourage venturing into feared situations.
GENERALIZED ANXIETY DISORDER

Generalized anxiety disorder (GAD) is characterized by intense
pervasive worry over virtually every aspect of life associated with
physical manifestations of anxiety. Accepted diagnostic criteria
for GAD are outlined in Table 4-5. The associated symptoms
highlight the physical and mental components of GAD.
TABLE 4-5. Diagnostic Criteria for Generalized Anxiety

Disorder
Anxiety and Excessive worry and anxiety for
worry most days over a 6-month period
about multiple events or situation
Uncontrollable Worry that is difficult to control
Associated Anxiety and worry are associated 1. Restlessness,
symptoms with at least three of six symptoms keyed up, on edge
2. Easily fatigued
3. Trouble
concentrating/blank
mind
4. Irritability
5. Muscle tension
6. Disturbed sleep
Context Focus of anxiety and worry does
not occur in the context of another
psychiatric disorder
Impairment The anxiety and worry
significantly impair social or
occupational function
Exclusion Anxiety and worry are not caused
by drugs, a general medical
condition, or other psychiatric
condition
EPIDEMIOLOGY
The lifetime prevalence of GAD is approximately 5%. The typical
age of onset is in the early 20s, but the disorder may begin at any
age.
ETIOLOGY
Twin studies suggest that GAD has both inherited and
environmental etiologies. Serotonergic, noradrenergic, and GABA-
ergic neurotransmitter systems have been studied in relation to
GAD, but the biologic etiology remains obscure. Cognitive-
behavioral theorists posit that GAD is caused by cognitive
distortions in which patients misperceive situations as dangerous
when they are not.

Patients with GAD worry excessively about virtually every aspect
of their lives (job performance, health, marital relations, and social
life). They do not have panic attacks, phobias, obsessions, or
compulsions; rather, they experience pervasive anxiety and worry
(apprehensive expectation) about a number of events or activities
that occur most days for at least 6 months. They must also have
difficulty controlling the worry, and it must be associated with at
least three of the following symptoms: restlessness, easily fatigued,
difficulty concentrating or mind going blank, irritability, muscle
tension, and sleep disturbance.
The focus of the anxiety and worry in GAD must not be
symptomatic of another Axis I disorder. For example, the anxiety
and worry cannot be about having a panic attack (as in panic
disorder) or being embarrassed in public (as in social phobia).
Similarly, if the anxiety and/or behaviors can be better explained
by the misperceptions that are common in psychotic or mood
disorders, then the patient would not be diagnosed with GAD.
MANAGEMENT
The pharmacologic treatment of GAD is with benzodiazepines,
buspirone (a nonbenzodiazepine anxiolytic), SSRIs, gabapentin, or
β-blockers. Although benzodiazepines are very effective, the
duration of treatment is limited by the risk of tolerance and
dependence. Relaxation techniques are also used in treatment with
some success.
KEY POINTS
Panic disorder is characterized by recurrent
unexpected panic attacks.
Agoraphobia is a separate condition from panic
disorder, but can co-occur.
Panic disorder responds to SSRIs and CBT.
Agoraphobia responds to exposure therapy not
medications.
Specific phobia is an intense fear of a specific
object, place, activity, or situation and occurs in
25% of the population at some point.
SAD is fear of exposure to scrutiny by others and
has a lifetime prevalence of 3% to 5%.
Treatment of SAD is with MAOIs, β-blockers,
SSRIs, alprazolam, or gabapentin and with CBT.
GAD is an intense, difficult-to-control worry over
every aspect of life associated with physical
manifestations of anxiety.
GAD is treated with benzodiazepines, buspirone,
SSRIs, β-blockers, gabapentin, and relaxation
techniques.
CLINICAL VIGNETTES
VIGNETTE 1
A 25-year-old woman has episodes of recurrent, unexpected anxiety,
with palpitations, diaphoresis, chest pain, and a fear of losing control
—symptoms consistent with panic attacks. She avoids socializing and
shopping because she fears the episodes will recur. She does not use
caffeine, psychostimulants, or take other medications. She has normal
thyroid function and normal blood pressure when not having a panic
attack. She has had a consultation with a cardiologist and the workup
included electrocardiogram, echocardiogram, and stress test with no
evidence of cardiac dysfunction.
1. Alterations in the following neurotransmitter system are strongly

linked to this disorder?
a. Glycine
b. Melatonin
c. Substance P
d. Enkephalin
e. γ-Aminobutyric acid (GABA)
2. The following brain regions are most strongly associated with

anxiety disorders:
a. The periaqueductal gray matter
b. The suprachiasmatic nucleus of the hypothalamus
c. Amygdala, prefrontal cortex, and hippocampus
d. The ventral striatum/nucleus accumbens
VIGNETTE 2
A 27-year-old graduate students presents to your office as his primary
care physician with complaints of feeling stressed out. He reports
constantly feeling anxious and tense, with daily worry about his life,
his family, and his friends. He feels fatigued and “tensed up” and has
trouble sleeping. He tosses and turns for an hour or so before falling
asleep but sleeps okay afterward. He remains interested in and
continues to enjoy his friends and hobbies. He does not endorse
sadness or depressed mood, increased guilt, change in appetite, or
suicidal thinking. The patient reports no use of psychostimulants and
limits caffeine only to a cup of coffee at breakfast. His physical exam
is normal and he appears anxious and keyed up. You order tests for
electrolytes, complete blood count (to rule out anemia as a cause of
the fatigue), urine drug screen to verify the absence of substances
that might produce these symptoms, and thyroid function tests.
1. Assuming that those tests are within normal limits, the most likely
diagnosis for this patient is:
a. Panic disorder
c. Social phobia
d. Agoraphobia
e. Generalized anxiety disorder (GAD)
2. The most appropriate initial pharmacotherapy for this patient

would include:
a. Bupropion
b. Lurasidone
c. Lamotrigine
d. Buspirone
e. Alprazolam
ANSWERS
1. Answer E:
The patient has the classic symptoms of panic disorder, a condition
diagnosed when there are recurrent panic attacks. Panic attacks are
defined as a discrete period in which intense fear or discomfort
develops out of the blue and in which symptoms peak in about 10
minutes. Symptoms of panic include palpitations, pounding heart, or
accelerated heart rate; sweating; trembling or shaking; sensations of
shortness of breath or smothering; feeling of choking; chest pain or
discomfort; nausea or abdominal distress; and feeling dizzy, unsteady,
lightheaded, or faint. Anxiety disorders have been most strongly
associated with alterations in the inhibitory neurotransmitter GABA.
Serotonin, norepinephrine, glutamate, dopamine, and peptide
neurotransmitters (CCK-4 and neuropeptide Y) are also implicated in
the pathophysiology of these conditions. Glycine is associated with
inhibitory transmission in the spinal cord. Melatonin is associated with
circadian rhythms and sleep disturbances. Substance P and
enkephalin are neurotransmitters most notably associated with pain.
2. Answer C:
Anxiety disorders have strong associations with fear and the
amygdala, a brain region having a key role in regulating the stress
response, is thought to play a central role in this regard. Regions of
prefrontal cortex and hippocampus are also important, serving as
processing or communicating structures in the manifestation of
anxiety. The periaqueductal gray matter is most strongly associated
with the descending pain processing system. The suprachiasmatic
nucleus of the hypothalamus has a primary role in responding to light
to entrain circadian rhythms. The ventral striatum/nucleus accumbens
region has a primary role in motivated behavior via responding to
prediction error signals for rewards.
1. Answer E:
GAD is characterized by intense pervasive worry over virtually every
aspect of life associated with physical manifestations of anxiety. The
condition is characterized by anxiety and worry about multiple events
and situations for most days over a 6-month period. Anxiety and worry
are associated with restlessness, feeling keyed up, on edge, feeling
easily fatigued, trouble concentrating/blank mind, irritability, muscle
tension, and disturbed sleep. Panic disorder is characterized by
recurrent, unpredictable panic attacks that peak within a few minutes
and subside and were not reported by this patient. Major depression is
unlikely because even though there is some symptom overlap
(decreased energy/fatigue, trouble concentrating, sleep disturbance)
between major depression and GAD, the patient reports an anxious
mood but does not endorse depression or anhedonia or other
neurovegetative symptoms. Social phobia is characterized by intense
fear of social situations such as a performance (also called
performance anxiety) that involves exposure to strangers or perceived
scrutiny by others. The anxiety in social phobia can be intense and
can lead to avoidance and a great deal of distress. Agoraphobia is a
condition most commonly associated with panic disorder in which
patients fear to leave their homes and actively avoid places (such as
public transport, widely open or enclosed places, and crowds) where it
might be hard to escape or obtain help.
2. Answer D:
Buspirone acts primarily as an agonist at the serotonin 1A receptor
and is approved for the treatment of GAD. Buspirone does not convey
an increased risk for developing a substance use disorder and does
not cause physiologic dependence. The patient should be informed
that the medication may require 2 to 4 weeks to have full effect.
Bupropion is effective as an antidepressant but is not used as first line
for GAD because of its tendency to have mild stimulant properties and
the potential to initially increase anxiety and insomnia. Lurasidone is
an atypical antipsychotic that is used in the treatment of psychosis and
bipolar depression but not specifically for GAD. Lamotrigine is a mood
stabilizer/anticonvulsant that is used in the treatment of bipolar
depression. Alprazolam is a short-acting benzodiazepine that is used
in the treatment of anxiety and that would likely alleviate many of this
patient’s symptoms. However, it conveys the risk for the development
of benzodiazepine use disorder and physiologic dependence and so is
not a good long-term treatment solution and would only be reasonable
if the patient had extreme distress.
While the Diagnostic and Statistical Manual of Mental Disorders,
Fifth edition (DSM-5) divides trauma- and stressor-related
disorders from dissociative disorders in their chapter structure,
these conditions have in common their association with an
unusually stressful life event or trauma. In addition, dissociative
symptoms are common in acute stress disorder and posttraumatic
stress disorder (PTSD). Depending on the specific trauma and the
person’s genetic risk profile, developmental level, and prior trauma
experiences, the trauma can result in an adjustment disorder, an
acute stress disorder, acute PTSD, chronic PTSD, a dissociative
identity disorder (DID), dissociative amnesia,
depersonalization/derealization disorder (DPD/DRD), or no
disorder at all (Table 5-1). (Reactive attachment disorder and
disinhibited social engagement disorder can occur in children as
trauma-related disorders but they will not be considered here.) The
trauma disorders can present with hyperarousal, fear, avoidance,
anxiety, flashbacks, or dissociation. Psychological trauma affects
memory, attention, and conscious awareness to varying degrees.
There appears to be a complex interaction between the
neurobiologic vulnerability to trauma, the effect of repeated life
trauma, and the evolution of traumatic disorders or dissociative
disorders.
TABLE 5-1. Trauma- and Stressor-Related Disorders and
Dissociative Disorders
Trauma- and Stressor-Related Dissociative Disorders
Disorders
Posttraumatic stress disorder Dissociative identity disorder
Acute stress disorder Dissociative amnesia
Adjustment disorder Depersonalization/derealization
disorder
POSTTRAUMATIC STRESS DISORDER

PTSD occurs when a person directly experiences or witnesses a
traumatic event. Symptoms of PTSD are grouped as intrusive,
avoidant, negative mood and cognition, and altered reactivity and
arousal (Table 5-2). The diagnosis (for individuals over 6 years
old) requires that a person demonstrate specific symptoms
following a traumatic event. DSM-5 criteria require the presence of
one or more of intrusive and avoidant symptoms and two or more
of symptoms of negative mood and cognition and altered reactivity
and arousal. Symptoms must persist beyond 1 month after exposure
to the trauma and cause significant distress in functioning. To
complete the diagnosis, the clinician should specify whether there
are associated dissociative symptoms such as depersonalization or
derealization. If the full symptoms do not appear until 6 months or
later after the stressor, delayed-onset PTSD is diagnosed.
TABLE 5-2. Diagnostic Criteria for Posttraumatic Stress

Disorder
Traumatic event(s) Direct or indirect exposure to traumatic
event or information
Intrusive symptoms (1 or Distressing memories
more) Distressing dreams
Dissociation (flashbacks)
Intense psychological distress
Physiologic reactions
Avoidance symptoms (1 or Avoidance of mental reminders
both) Avoidance of physical reminders
Negative mood and Loss of memory for part of the event
cognition (2 or more) Excessive negative beliefs
Distortion in cognition
Negative emotions
Diminished interest
Feeling detached or estranged
Lack of positive emotions
Altered reactivity and Irritability and anger
arousal (2 or more) Reckless or self-destructive
Hypervigilance
Increased startle
Impaired concentration
Disturbed sleep
EPIDEMIOLOGY
The prevalence of PTSD is estimated at 0.5% among men and
1.2% among women. PTSD may occur at any age from childhood
through adulthood and may begin hours, days, or even years after
the initial trauma.
ETIOLOGY
The central etiologic factor in PTSD is the trauma. There may be
some necessary predisposition to PTSD because not all people who
experience similar traumas develop the syndrome. Smaller
hippocampal volume is associated with PTSD, with the possibility
that small hippocampal volume may predispose to the development
of PTSD on exposure to trauma but also that trauma may lead to
loss of hippocampal volume.
NEURAL BASIS
Both congenital and experiential effects on the nervous system can
lead to increased risk of developing PTSD or related stress
disorders. The neurobiology of PTSD is complex and involves
multiple brain regions and intercommunication between brain
networks, whose dysfunction is thought to mediate specific
symptoms. Figure 5-1 outlines brain regions implicated in PTSD.
FIGURE 5-1. Brain regions implicated in posttraumatic stress disorder

(PTSD). Multiple brain regions are implicated in the neurobiology of
PTSD symptoms. dmPFC, dorsomedial prefrontal cortex; rmPFC,
rostral medial prefrontal cortex; vmPFC, ventromedial prefrontal
cortex; ACC, anterior cingulate cortex. (From Sadock BJ, Sadock VA,
Ruiz P. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry,

People with PTSD have endured a traumatic event (e.g., combat,
physical assault, rape, explosion) in which they experienced,
witnessed, or were confronted with actual or potential death,
serious physical injury, or a threat to physical integrity. The
traumatic event is subsequently reexperienced through repetitive
intrusive images or dreams or through recurrent illusions,
hallucinations, or flashbacks of the event. In an adaptive attempt,
these patients make efforts to avoid recollections of the event, often
through psychological mechanisms (e.g., dissociation, numbing) or
actual avoidance of circumstances that will evoke recall. They also
experience feelings of detachment from others and exhibit evidence
of autonomic hyperarousal.
Substance abuse comorbidity is extremely common and often
needs to be treated before effective PTSD treatment can
commence. Many patients with PTSD suffer for years or decades
using substances and other distracting stimuli to cope. Many
attempt or complete suicide without ever receiving the treatment
needed. Some patients with PTSD develop chronic dissociation and
may evolve a dissociative identity disorder (DID), discussed later
in the chapter.
Symptoms that resemble PTSD may be seen in depression,
generalized anxiety disorder, panic disorder, obsessive-compulsive
disorder (OCD), and dissociative disorder. When symptoms
resemble PTSD, verify that there are also symptoms from all three
categories; if not, consider one of the previously mentioned
diagnoses.
MANAGEMENT
Treatment is with a combination of symptom-directed
psychopharmacologic agents and psychotherapy (individual or
group). Selective serotonin reuptake inhibitors (SSRIs) are first-
line pharmacotherapies and appear to be the most effective
medication treatment for reducing symptoms of PTSD. Less
evidence is available for other antidepressants and atypical
antipsychotics. The α-2 antagonist, prazosin, has been
demonstrated to be effective in treating nightmares and insomnia.
Psychotherapy is effective and is typically tailored to the nature of
the trauma, degree of coping skills, and the support systems
available to the patient. Increasing the patient’s tolerance of
recollections of the event(s) and restructuring cognitive appraisal
appear to be mechanisms of psychotherapeutic recovery.
ACUTE STRESS DISORDER

Acute stress disorder will not be reviewed in detail, but the
diagnostic criteria are very similar to those for PTSD. Acute stress
disorder, as the name implies, is an acute, self-limited condition
lasting for a minimum of 2 days and a maximum of 4 weeks. This
condition must also have its onset within 4 weeks of exposure to a
traumatic event. The major difference between a diagnosis of acute
stress disorder and PTSD is symptom length. An individual
initially diagnosed with acute stress disorder could be subsequently
diagnosed with PTSD if severe symptoms persist beyond 4 weeks
after trauma exposure. Treatment interventions during acute stress
disorder may help prevent development of PTSD, but much
additional research is needed in this regard.
ADJUSTMENT DISORDER
Adjustment disorder is diagnosed when a patient presents with
symptoms of anxiety, depression, conduct, or emotions that fail to
meet criteria for another mental disorder and appear within 3
months in reaction to a stressful event (e.g., a loss or life change).
The symptoms must include marked distress and functional
impairment. The condition is self-limited once the stressful event
or its aftermath have ceased.
EPIDEMIOLOGY
Estimates of prevalence vary widely in studies and appear to be
more common in those seeking outpatient or inpatient mental
health treatment. Prevalence ranges from 5% to 20% in outpatients
to more than 50% among acute inpatients.
ETIOLOGY
The cause remains unknown, but it appears that physiologic
reactions to stressful life events may lead to anxiety or other mood
symptoms (e.g., sleep disturbance, restlessness, anxiety attacks).
Patients from low socioeconomic backgrounds or those who have
experienced trauma in the past appear to be more at risk.

Patients often present with no prior significant psychiatric history
in the aftermath of a life event that appears to have overwhelmed
them. The event is often new and unexpected, but can be chronic
and experienced vicariously. Cultural determinants of perception of
the event should be taken into account to make an accurate
diagnosis. They can present with any number of mood or anxiety
symptoms. They may have suicidal thoughts or thoughts of
violence and are at increased risk of acting on these thoughts in an
impulsive manner. The mental status examination is usually normal
from a cognitive standpoint, and there are no distinct disturbances
of thought. Mood and affect are most affected. Emotional
expressions out of proportion to the patient’s normal affect are
common.
The patient should have a thorough psychiatric evaluation with
consideration of any possible medical or psychiatric comorbidity.
Bereavement requires more extensive enquiry to determine whether
the patient’s reaction, in life or culture, is within normal limits or
disproportionate. This can be challenging to discern and may
require discussion with the patient’s family or review with peers.
The risk assessment for suicidal or homicidal behavior is critical.
The patient is at risk for developing more severe mental disorders if
left untreated, so taking a careful history with corroboration of the
time frames of onset and the range of symptoms is helpful.
Major depression, anxiety disorder, or traumatic disorder must be
ruled out depending on severity and duration of symptoms.
Treatment should be planned with the idea in mind that the
symptoms may evolve into one of these conditions. Fortunately, the
medication and therapy treatment options are similar. This
diagnosis is usually thought of as a “diagnosis of exclusion.” If the
patient is presenting with some symptoms of a major mental
disorder but does not fully meet the criterion of any other disorder
and there is a clear precipitant, then the diagnosis can be made. The
stressor may be more traumatic to the patient than you at first
perceive and the patient may in fact have an acute stress disorder or
develop PTSD. Carefully consider the patient’s long-term coping
style and whether the presentation may be a manifestation of a
personality disorder (e.g., borderline personality disorder can
present with marked distress in reaction to life events).
MANAGEMENT
Management of adjustment disorder is largely supportive and
targeted at the specific symptoms. Displaying empathy and
reframing the stressor in light of the patient’s life story are usually
the first-line approaches. Medication may be needed to address
specific symptoms, such as insomnia. A brief, targeted course of
cognitive-behavioral psychotherapy demonstrates the best
outcomes with fewer long-term complications.
DISSOCIATIVE DISORDERS
Dissociative disorders are a collection of related disorders that are
characterized by alterations in sensory perception, memory,
identity, and/or conscious awareness that impair an individual’s
ability to function socially, occupationally, or in other important
areas of function. Although not considered traumatic disorders, the
dissociative disorders are closely related to trauma and symptoms
of dissociation occur in the traumatic disorders. Persistent
disturbances of memory perception or identity not due to a
neurocognitive disorder or psychosis are often the result of some
type of dissociative disorder. Table 5-3 helps identify the pattern of
symptoms associated with each of the three major dissociative
disorders.
TABLE 5-3. Dissociative Disorders
Disorder Identity Derealization/Depersonalization Amnesia
Disturbance
Dissociative Yes No Yes
amnesia
DPD/DRD No Yes No
DID Yes Yes Yes
DID, dissociative identity disorder; DPD/DRD, depersonalization/derealization disorder.
DISSOCIATIVE IDENTITY DISORDER

DID, sometimes referred to by nonclinicians as multiple
personality, is a complex disorder that appears to form from severe
early childhood trauma and can present from young childhood
through late life. The essential criteria are having two or more
distinct personalities or a sense of being possessed. It is
characterized by recurrent behaviors in which the person appears to
have separate and distinct personality features, speech patterns, and
ways of thinking and acting in the world that are distinct from their
native identity. The patients often are not aware that they “switch”
into alternate identities until circumstances surrounding the
alternate behavior leads to a revelation or legal ramifications force
it into their awareness. The patients often still remain amnestic to
the episodes even when they are aware that they are occurring.
Sometimes the alter identities are not well-formed separate
identities, but rather fragments of a personality or emotional state
that may or may not be capable of adequately communicating.
These disorders are challenging to diagnose and often lead to
confusion or skepticism on the part of family, friends, and even
clinicians because the presentation can be so variable and fantastic
as to be unbelievable. However, these conditions do appear to
occur with measurable frequency and result in sometimes severe
harm to self or others.
EPIDEMIOLOGY
DID appears to occur in 1.4% to 1.6% of the population—a higher
frequency than schizophrenia and with a slight predominance of
male versus female sufferers.
ETIOLOGY
The cause of DID is unknown and is believed to involve both
neuropsychological, psychological, and social-emotional etiologic
mechanisms. It appears that severe early life trauma or neglect are
the usual antecedents, but in some cases no traumatic history is
evoked and the antecedent cause is unexplained. Head trauma from
early childhood abuse, preverbal dissociation, and abstract social
emotional processing can make the disorder more complicated or
severe. The genetic risk of other mental disorders may be higher
than average in patients with DID because of the higher prevalence
of personality disorders, severe mood disorders, and substance use
disorders in families with chaotic, neglectful, and/or abusive
environments. Early childhood or infantile sexual abuse appears to
be a major risk factor for DID. Dissociative identity and
dissociation, in general, may be an adaptation that allows the
individual to cope with overwhelming trauma.
NEURAL BASIS
The neural basis of DID is unknown, but its overlap with PTSD
and amnestic disorders make it likely that the basis involves the
memory circuitry and fear response circuitry including the
hippocampus and amygdala. There may also be separate neural
pathways that are activated in particular dissociative states that
mediate the amnesia for the differential states of being.

Patients with DID rarely initially present complaining of their core
symptomatology because they are usually unaware of its existence
or extent. Instead, they may present with other mood, anxiety, or
traumatic symptoms and through the course of treatment may
manifest clear episodes of dissociation. DID should be suspected
whenever there are distinct fluctuations in a patient’s mood or
behavior, particularly when the patient does not seem to recognize
the changes. A history of childhood neglect or abuse as evidenced
by self-report or reports of being taken from the home by social
services, or time spent in foster care can be a clue to the nature of
the disorder. Patients with true DID will usually not be pleased that
they have the disorder or offer it up as a diagnosis. Rather, they are
more often indifferent or confused about the presentations. The
mental examination may be completely normal depending on the
state of the condition at the time of examination. The patient can
also present as mute or with an aberrant speech pattern or accent.
Their appearance can vary in terms of style of dress, gender
presentation, age, developmental level, or personality expression.
Usually, there is some evidence of lost time or amnesia, but this
may be difficult to discern at first.
There is a long differential diagnosis that includes PTSD, other
mood disorders, seizure disorder, amnestic disorders, and
malingering. Patients with PTSD can present with dissociation,
derealization, or depersonalization; but they generally do not have
distinct separate identities. Patients with personality disorders can
present with sudden shifts of mood, perception, or behavior about
which they are usually aware. Partial complex seizures can result in
alternate behaviors, of which the patient has no recollection. Severe
bipolar disorder or schizophrenia can be complicated by catatonia
that can result in aberrant or unusual excited behavior or alterations
in consciousness, responsiveness, or speech that could make one
think the patient has a separate identity. Similarly, if a patient has
amnesia from head trauma or a metabolic disorder, he or she may
not have identity recall and may take on different personalities or
representations in the state of unawareness of native identity.
MANAGEMENT
Management of DID should be based on expert consensus
guidelines. Sequentially staged trauma-focused therapy is
recommended for patients with DID. Initially, the therapy focuses
on stabilizing the patient and forming an alliance, followed by
processing traumatic experiences with the ultimate goal of
integrating the dissociated identities.
DISSOCIATIVE AMNESIA
Dissociative amnesia can be selective amnesia for a specific,
usually traumatic life event, or can consist of a broader amnesia for
important autobiographical information such as personal identity. It
is a condition that can also be associated with a fugue state in
which a person engages in sudden wandering or travel in response
to a traumatic event. The person usually is amnestic to the reason
for the trip.
EPIDEMIOLOGY
The prevalence is approximately 1.8% with more women than men
presenting with the condition.
ETIOLOGY
The etiology of the condition is unknown, but dissociative amnesia
is often associated with traumatic events and is more common after
more severe trauma. It is hypothesized that the amnesia is
psychological in origin because the traumatic event is emotionally
intolerable to the patient.
NEURAL BASIS
In dissociative amnesia, the memories are encoded in the brain;
however, the patient loses access to the information. The
mechanism of losing access is unknown, but it may be related to
hypofunction of frontotemporal cortex.

The patients with dissociative amnesia are more likely to report a
history of trauma and to have difficulty in maintaining
relationships. On mental status examination, they may appear to be
normal in every respect except for the notable absence of
autobiographical memory or of the associated event or they can
have anxiety symptoms. They do not have general memory
problems, and their ability to register new memories is unimpaired.
DID and PTSD must be ruled out. Similarly, substance use or
neurocognitive impairment due to seizures, dementia, or traumatic
brain injury should be ruled out. Lastly, malingering or factitious
disorder can present as a selective amnesia.
MANAGEMENT
Patients with dissociative amnesia can be emotionally fragile and
must be carefully approached. Suicide risk seems considerably
elevated in this condition. They need to develop a trusting alliance
with a consistent and empathic therapist to begin to talk about past
traumatic events. In the course of that work, they may be able to
recover the lost memories and reframe the events in a manner that
allows them to remain in conscious awareness. Pharmacologic
treatment is not available to reverse the amnesia, but associated
anxiety or other symptoms may be treated as they emerge in the
course of treatment. Patients may resolve the amnesia, but they are
at high risk for recurrent bouts of dissociative amnesia particularly
if there are recurrent traumatic events.
DEPERSONALIZATION/DEREALIZATION
DISORDER
The core features of DPD/DRD are recurrent bouts of feeling alien
to oneself or to the outside world or to both. The symptoms may
include (1) depersonalization: bodily or emotional sensations
including not feeling like a real person, feeling physically “numb”
or feeling that one’s thoughts are clouded or not real or even
having an “out of body” experience and (2) derealization: the
sensation of being disconnected with the outside world or
perceiving objects in the environment as larger, smaller, or a
blurriness/cloudiness of visual field.
EPIDEMIOLOGY
Transient lifetime prevalence of derealization and
depersonalization experiences is quite high, and may approach
50%. However, the full disorder is less common with an estimated
prevalence in the United States of around 2%.
ETIOLOGY
Derealization and depersonalization have temperamental and
environmental antecedents. Persons at risk for the disorder have a
temperament that is characterized by harm-avoidance and the use
of projection and denial as defenses. They have more often not
been the victims of early childhood traumas and adverse events
leading to difficulties emotionally managing adult life stressors.
The derealization/depersonalization is thought to be a complex
neurobiologically mediated coping mechanism that is deployed to
manage overwhelming feelings.
NEURAL BASIS
Studies on the neurobiology of DPD/DRD have implicated sensory
cortices, the dorsolateral and ventrolateral prefrontal cortices, and
their connection to the cingulate gyrus and the amygdala.

Patients with DRD/DPD are more likely to report a history of early
childhood turmoil and trauma. They often exhibit marked
difficulties in managing relationships and can have prior episodes
of self-mutilation or suicidal behavior. Immature coping defenses
and limited self-awareness are commonly noted. On examination,
the patients may have limited insight and poor judgment about their
experience. They often will have normal appearance and exhibit
mood, affect, and thought processes that are in the normal range.
Their intelligence and problem-solving abilities will often be below
average.
Ruling out other diagnoses that would also include derealization or
depersonalization including PTSD, dissociative amnesia, and DID
is important. However, a broader range of psychiatric disorders can
also present with derealization and depersonalization, including
major depression, OCD, anxiety disorder, and psychotic disorders.
A common cause of derealization or depersonalization is the use or
abuse of substances including stimulants, PCP, ecstasy, ketamine,
LSD, and synthetic cathinones (“bath salts”). Prior use of drugs and
recent use of unknown substances can lead to the diagnosis.
MANAGEMENT
As with other disorders involving trauma and coping mechanisms,
a reliable, empathic psychotherapeutic approach is most effective.
Through the use of cognitive-behavioral therapy and dialectical
behavior therapy, the patient can develop more adaptive coping
strategies to manage routine adult stressors. Treatment-emergent
mood and anxiety shifts can be treated with medication, being
careful not to use substances such as benzodiazepines that might
provide temporary relief but could lead to dependence, withdrawal,
and further anxiety.
KEY POINTS
Lower hippocampal volume may be a risk factor
for and a consequence of PTSD.
The neurobiology of PTSD is complex and
involves multiple brain regions and networks.
In adjustment disorder, patients present with
symptoms of anxiety, depression, or disturbed
conduct.
Patients with DID may have multiple alters.
In depersonalization/derealization disorder,
patients feel alien to themselves or the outside
world or both.
CLINICAL VIGNETTES
VIGNETTE 1
A 36-year-old Caucasian woman presents to the emergency
department in a confused state not able to respond to questioning at
first. She is found rocking and holding herself in a chair. She has
obviously been crying and appears overwhelmed. After you sit near
her for a few minutes, she stops rocking and you begin to ask some
basic questions. At first she does not respond, but then she starts
answering with one-word answers. Because she looks so frightened,
you ask, “Are you safe?” She replies, “No.” You assure her that no
one will try to hurt her and she screams “how do YOU know?” You tell
her that nurses and doctors are all around the emergency room (ER)
and that they will make sure no one hurts her. A few minutes later, she
appears to calm letting her arms fall to her side. You begin to listen to
her as she tells her story. She was at her therapist’s office and she
told her that she was closing her practice in a month and that she
would be referred to another therapist. She begins to cry and tells you
that she has seen the therapist for 3 years—the longest she has ever
seen a provider. She says she does not think she will find another like
her. You make an empathic statement and she appears to calm
further. She reports that she was abused physically and sexually by
numerous relatives and acquaintances throughout her childhood
extending into early adulthood. She reports that she has had
nightmares and flashbacks since early adulthood and has been
unable to work or function. She has also developed numerous health
problems including hypertension, diabetes, and chronic pain. She
denies persistent depressed mood or suicidal ideation. She also
denies prior suicide attempts or self-destructive behavior or any recent
head trauma or drug use. You ask her if it is OK to do a brief
examination and draw some laboratory work. She says, “Yes.” After a
brief exam, you enter an order for a complete blood count,
electrolytes, glucose level, urine drug screen, and hemoglobin A1c.
You leave the room and return 45 minutes later. She appears
frightened when you enter the room and says, “Who are you?” You
say, “I am your doctor, we just spoke before.” She says, “No we didn’t
—no one has come to speak with me yet.” You are confused but begin
explaining that her blood sugar is elevated but that all the other tests
look normal. “I don’t recall having any blood drawn—it must be
someone else’s bloodwork.” Confused, you walk out and ask the
nurse if she drew the right patient’s blood. She says yes but that the
patient was behaving strangely after the blood draw and did not seem
to know where she was any longer. You think you understand what
may be happening.
1. What is the most likely diagnosis?

a. Major depression, severe
b. Borderline personality disorder
d. Amnestic disorder
d. Acute stress disorder
e. Dissociative identity disorder
2. What would be the most reasonable next step for this patient?
a. Immediately admit her to the hospital to treat her blood sugar.
b. Stabilize her blood sugar in the ER and reconnect her with
outpatient care.
d. Hold her in the ER with no treatment for 23 hours.
d. Release her to her own care with a referral back to her primary
care doctor.
e. Injection with ziprasidone and lorazepam to calm her and make
her sleep.
VIGNETTE 2
A 23-year-old woman is brought into the ER on a stretcher with a neck
brace and a back board after an automobile accident. The surgeon on
duty begins to examine her to determine if she has sustained any
serious injury. She is tearful and appears frightened but cooperates
with the examination. She is sent for x-rays of the cervical spine and
then a computed tomography scan of the chest because of some blunt
chest trauma from the airbag deployment. All the tests are normal,
and she is prescribed some ibuprofen and told to take 3 days off from
her job and rest. A week later she returns looking distressed. She
reports that she hasn’t been sleeping well and has little appetite. She
keeps playing the accident over and over in her mind as if she is
reliving it. She has been afraid to drive and even has had difficulty
being a passenger in a car. She has nightmares as well largely related
to the accident scene. She reports that she has returned to work and
she enjoys being there but the commute to and from work has been
very stressful. You reassure her that her symptoms are natural and
that they should subside within a few weeks. In the meantime, you
recommend talking to a counselor and taking a mild sleep aid.
1. If the patient’s symptoms do subside before 4 weeks have

elapsed, the most likely diagnosis is:
a. Acute stress disorder
b. Posttraumatic stress disorder, severe
d. Adjustment disorder
d. Anxiety disorder
e. Malingering
VIGNETTE 3
A 24-year-old Hispanic man presents to the ER intoxicated with
alcohol after being picked up by the police at a bar where he had
gotten into a fight. He appears distressed and looks disheveled on
arrival. After he gets a medical assessment and some blood drawn,
you enter the room to speak to him. He tells you that he has done
two tours of duty in Afghanistan and that he was deployed to the
improvised explosive device (IED) team that had to find hidden
explosives and deactivate them. There were several instances
where he witnessed a colleague getting killed instantly when an
IED exploded. He came close a few times himself to being
seriously injured or killed and spent months fearing for his life
every day while on these missions. During the deployment, he was
on “high alert” but he did not seem to be emotionally upset about
the events. However, since his last return to civilian life, he has
begun having nightmares about being on the mission in which he is
just about to step on an IED. Also, he finds himself daydreaming
and feels like he is back on the field taking careful steps and
hearing the bombs go off in his mind. It scares him and puts him
back on “high alert” where he feels anxious and hyperaware of his
surroundings. He has been back from the last mission for 3 months
and the symptoms have persisted. He has begun drinking more
alcohol because he feels that it calms his nerves, something he
discovered while deployed. He has started to avoid some friends
and family obligations. He denies feeling suicidal currently but
says he has had thoughts that he might be better off dead.
a. Acute stress disorder
b. Posttraumatic stress disorder
d. Panic disorder
e. Agoraphobia
2. What comorbid condition is the patient most at risk for

developing?
a. Suicide
b. Dissociative identity disorder (DID)
d. Bipolar disorder
d. Obsessive-compulsive disorder
e. Alcohol use disorder
ANSWERS
1. Answer E:
The patient presents initially with symptoms consistent with
posttraumatic stress disorder (PTSD), including nightmares and
flashbacks with a history of physical and sexual abuse. However,
when the patient fails to recall your encounter and appears to be
experiencing that encounter as a new one, she appears to have
“switched” into an altered personality. It is important to rule out simple
amnestic disorder, but in the context of severe psychological trauma
and with no known recent head injury, a simple amnestic disorder is
less likely. Although the patient is presenting with tearfulness and
anxiety, she denies persistent depressed mood and suicidal ideation
and does not appear to meet criteria for a major depression. Similarly,
she denies the self-destructive or suicidal behavior that would be more
typical of a patient with borderline personality disorder. Since her
stressors date back to childhood and she has had active PTSD
symptoms for some time, an acute stress disorder would not be an
appropriate diagnosis.
2. Answer B:
Stabilize her blood sugar and reconnect her with outpatient care.
Patients with DID require caution in care because of the volatility of
the disorder, the risk of unsafe activity occurring when in their
dissociative states, and the lack of trust that patients with severe
trauma often have of the clinician when they begin treatment. The
therapist or doctor may inadvertently trigger traumatic dissociation
with their words, facial expression, style of dress, or behavior. It is
possible that the blood draw triggered a dissociative episode. Often,
the therapist or doctor is one of a few or the only support that the
patient has at treatment initiation. Once a treatment plan is initiated for
the blood sugar, making a call to the therapist and reconnecting her
with outpatient care would be the best next option. Unless her blood
sugar is dangerously high, she would not need an admission. Holding
her in the ER would not make her feel safe nor would it reconnect her
with the caregiver that she trusts. Although she may need a referral
back to a primary care doctor for long-term management of her
diabetes, this is not the primary issue currently. Finally, although it
may seem helpful to alleviate her distress with sedative medications, it
is more prudent to help her process the feelings that she has about
her therapist’s departure with a clear mind.
1. Answer A:
The patient presents with all the common symptoms of PTSD
including nightmares, flashbacks, and anxiety. The automobile
accident with airbag deployment and possible life-threatening injury
are certainly enough to evoke a traumatic reaction. However, to be
diagnosed with PTSD, she must have symptoms that persist for more
than 4 weeks. An adjustment disorder would be a possible diagnosis if
she did not have the nightmares and flashbacks characteristic of a
more severe traumatic reaction. And, although she has anxiety
symptoms, this alone does not explain her full symptom profile.
Finally, patients with malingering usually have a secondary gain to be
achieved by reporting the symptoms. Since she has returned to work
and does not appear to be asking for continued excuse from job
duties, malingering seems unlikely.
1. Answer B:
People with PTSD have endured a traumatic event (e.g., combat,
physical assault, rape, explosion) in which they experienced,
witnessed, or were confronted with actual or potential death, serious
physical injury, or a threat to physical integrity. The traumatic event is
subsequently reexperienced through repetitive intrusive images or
dreams or through recurrent illusions, hallucinations, or flashbacks of
the event. In an adaptive attempt, these patients make efforts to avoid
recollections of the event, often through psychological mechanisms
(e.g., dissociation, numbing) or actual avoidance of circumstances that
will evoke recall. They also experience feelings of detachment from
others and exhibit evidence of autonomic hyperarousal. The duration
of his symptoms rules out a self-limited acute stress disorder.
Similarly, the symptoms are too severe and include flashbacks and
nightmares, ruling out a less severe adjustment disorder. And,
although he does present with anxiety, he does not describe discrete
panic episodes and the anxiety seems to be related to his flashbacks
and traumatic experiences. Finally, although he has been avoidant of
social situations, he does not describe a fear of being in public or
being with people that would be characteristic of agoraphobia.
2. Answer E:
Substance abuse comorbidity is extremely common in PTSD and
often needs to be treated before effective PTSD treatment can
commence. He is already experiencing some early symptoms of
alcohol use disorder and presented with intoxication leading to a
police-involved altercation. Many patients with PTSD suffer for years
or decades using substances and other distracting stimuli to cope.
Many attempt or complete suicide without ever receiving the treatment
needed; however, he presents with passive suicidal ideation without a
plan currently. There are no symptoms that suggest bipolar disorder,
but a patient with his condition would be at higher risk of developing
either major depressive disorder (a unipolar mood disorder) or bipolar
mood disorders. People with PTSD can also develop rituals or
obsessions related to the trauma or efforts to avoid recollections, and
symptoms can be suggestive of obsessive-compulsive disorder, but
this patient does not appear to have any specific obsessions or
compulsions. Finally, although patients with PTSD can go on to
develop DID, they usually have some history of early childhood
trauma and would normally present with lost time or other dissociative
symptom clues.
Obsessive-compulsive and related disorders is a category of mental
illnesses characterized by obsessive thoughts and/or repetitive
compulsions. Obsessions are recurrent intrusive or unwanted
thoughts, images, or urges. Compulsions are actions, behaviors, or
mental acts that the person feels compelled to perform repeatedly,
on a specific schedule or a certain rhythm. The most prominent of
these diagnoses is obsessive-compulsive disorder (OCD),
characterized by a broad range of obsessions and compulsions that
are severe and persistent enough to adversely affect social and/or
occupational functioning.
OCD-related conditions involve a misperceived sense of
appearance (body dysmorphic disorder), repetitive compulsion to
hoard objects (hoarding disorder), hair-pulling (trichotillomania),
or picking at skin (excoriation disorder) (Table 6-1). In addition to
the primary psychiatric disorders, symptoms of OCD and related
disorders can be brought on by medications or substance use and
can occur in association with other medical conditions. Anxiety
disorders and major depression often co-occur with OCD and its
related disorders.
Each condition can be characterized by good or fair insight,
poor insight, or no insight into the veracity of the beliefs. Some
common subtypes of beliefs or perceptions are recognized as
subtypes as well.
TABLE 6-1. Obsessive-Compulsive Disorder and Related
Disorders
Obsessive-compulsive disorder
Body dysmorphic disorder
Hoarding disorder
Trichotillomania (hair-pulling disorder)
Excoriation (skin-picking disorder)
NEURAL BASIS
OCD has been linked to altered function in prefrontal regions
(medial and lateral orbitofrontal cortices), the dorsal anterior
cingulate cortex (dACC), the caudate and amygdala. Serotonin
modulation appears to mitigate the symptoms, suggesting a role for
altered serotonin in this condition. Refractory cases can be treated
with caudate stereotactic neurosurgery or anterior cingulotomy of
the dACC. The related conditions appear to be related genetically
and are presumed to have a similar neural basis.
OBSESSIVE-COMPULSIVE DISORDER
EPIDEMIOLOGY
The lifetime prevalence of OCD is 2% to 3%. Typical onset of the
disorder is between the late teens and early 20s, but one-third of
patients show symptoms of OCD before age 15.
ETIOLOGY
Behavioral models of OCD claim that obsessions and compulsions
are produced and sustained through classic and operant
conditioning. Interestingly, OCD is seen more frequently after
brain injury or disease (e.g., head trauma, seizure disorders,
Huntington’s disease), and twin studies show that monozygotic
twins have a higher concordance rate than dizygotic twins; these
findings support a biologic basis for the disorder. The
neurotransmitter serotonin has been implicated as a mediator in
obsessive thinking and compulsive behaviors. Neuroimaging
evidence to date suggests that multiple brain regions are affected.

Patients with OCD experience obsessions and compulsions.
Obsessions are recurrent intrusive ideas, thoughts, or images that
cause significant anxiety and distress; compulsions are repetitive,
purposeful physical or mental actions that are generally performed
in response to obsessions. The compulsive “rituals” are meant to
neutralize the obsessions, diminish anxiety, or somehow magically
prevent a dreaded event or situation. The level of insight can vary
from good insight to poor or no insight in which the person
believes that the obsessions or the consequences of not performing
the compulsions are likely true or definitely true. Previously, this
would have made the condition a delusional or psychotic disorder.
Now, it is accepted that severe OCD can have a delusional
component. Table 6-2 lists common obsessions and compulsions.
TABLE 6-2. Common Symptoms in Obsessions and

Compulsions for Obsessive-Compulsive Disorder
Variable %
Obsessions (N = 200)
Contamination 45
Pathologic doubt 42
Somatic 36
Need for symmetry 31
Aggressive 28
Sexual 26
Other 13
Multiple obsessions 60
Compulsions (N = 200)
Checking 63
Washing 50
Counting 36
Need to ask or confess 31
Symmetry and precision 28
Hoarding 18
Multiple comparisons 48
Course of illness (N = 100)a
Type
Continuous 85
Deteriorative 10
Episodic 2
Not present 71
Present 29
aAge at onset: men, 17.5 6.8 years; women, 20.8 8.5 years.
Adapted from Rasmussen SA, Eiser JL. The epidemiology and differential diagnosis of obsessive
compulsive disorder. J Clin Psychiatry. 1992;53(4 suppl):6. Reprinted with permission from
Springer Nature.
It is important to distinguish the obsessional thinking of OCD from
the delusional thinking of schizophrenia or other psychotic
disorders. Obsessions are usually unwanted, resisted, and
recognized by patients as coming from their own thoughts, whereas
delusions are generally regarded as distinct from patients’ thoughts
and are typically not resisted. Some patients with OCD will hold
the fixed, false belief that their obsession or compulsion or its
consequences are real, and are technically delusional in this sense.
MANAGEMENT
Cognitive-behavioral therapy (CBT), clomipramine, and selective
serotonin reuptake inhibitors (SSRIs) have been shown to be quite
effective in treating OCD. Although poorly studied, the behavioral
techniques of systematic desensitization, flooding, and response
prevention have been used successfully to treat compulsive rituals.
For example, someone who fears contamination from an object will
hold the object repeatedly in therapy while simultaneously being
prevented from carrying out the ritual associated with the dreaded
object. Severe unremitting OCD that has failed to respond to
multiple modalities of treatment may be treated with neurosurgical
intervention targeted at brain regions that control the repetitive
thoughts and impulses.
BODY DYSMORPHIC DISORDER

The condition is similar to OCD, but the focus is specifically on the
perception that the person has a defect in some aspect of their
appearance. The belief can involve any part of the body and any
degree of appraisal. The person needs to be obsessed with the
defect to a point where he or she spends significant amounts of
time and effort assessing and trying to correct the defect. There is a
subtype specifier called muscle dysmorphia for patients who have
a preoccupation that their musculature is too small or insufficient.
EPIDEMIOLOGY
The condition affects approximately 2.5% of US adults (slightly
more women than men). It appears to be more common in the
United States than in other parts of the world but is seen in more
than 1% of the world’s population.
ETIOLOGY
The specific etiology is unknown. First-degree relatives of those
with OCD are more likely to develop body dysmorphic disorder,
contributing to the theory that they have an underlying common
etiology. The higher prevalence in the United States suggests a
cultural influence on the development of the disorder.
Patients with body dysmorphic disorder present in a myriad of
ways, often to a provider such as a dermatologist or a dermatologic
or plastic surgeon whom they believe could “fix” the perceived
defect. Usually, those close to the patient have been queried many
times about the defect and their appraisal.

Patients are quite likely to explain in great deal how their body or
its parts are defective or ugly. Usually, it is unclear when the
perception began. Patients usually describe having “always” been
this way. They appear to perceive the body part differently than
others and appear unwilling to entertain an alternative viewpoint.
The examination should result in a largely normal mental status
except for the thought content centering around the perceived
defect.
Perceptions of body image that are distorted can appear in eating
disorders, depression, and psychotic disorders. They key to
differentiating is to look for the other signs and symptoms of the
alternative diagnoses.
MANAGEMENT
Patients are often managed in consultation with the provider who
has been asked to repair the defect. It is important to respect the
patient’s perception and his or her desire to correct it while at the
same time beginning to use medication and therapy to help the
patient relinquish the belief. The goal should be to prevent the
patient from pursuing risky surgery or self-destructive behavior and
to accept their appearance to the degree that they are able to. SSRIs
have some effect on the intensity of the dysmorphic perceptions but
must be combined with CBT to make an impact. The prognosis is
poor in terms of remission but better if the expectations of outcome
are more moderate.
HOARDING DISORDER
Hoarding disorder is characterized by a persistent difficulty in
parting with or discarding possessions, leading to an impairing
level of clutter of living areas. The fear of loss or that one might
need the objects in the future appears to sustain the collecting. In
some cases, it is the lack of discarding periodically that leads to
overaccumulation and clutter. In other cases, the person actually
actively collects or hoards many more items than he or she needs
and fails to discard. The condition usually comes to attention when
authorities are alerted to the unsafe and sometimes squalid
conditions. This happens when sanitary issues related to garbage,
pet waste, and human waste are not properly handled. Fire and
escape hazards can also occur from the clutter, which can reach the
ceiling height and lead to only a small path through the home. The
majority of sufferers have a comorbid mood and/or anxiety
disorder.
EPIDEMIOLOGY
Hoarding disorder affects 2% to 6% of the population in the United
States and Europe. Seventy-five percent of patients have a
comorbid mood or anxiety disorder.
ETIOLOGY
The specific etiology is unknown. Approximately 50% of people
with hoarding disorder have a relative with hoarding behavior.
Early psychological trauma as well as an indecisive temperament
are risk factors.

Patients with hoarding disorder usually begin hoarding in their late
childhood or early teen years. The condition usually progresses
over decades and can worsen in late life in terms of functional
impact. Patients do not usually present for treatment voluntarily,
but usually at the insistence of authorities or family after hoarding
has occurred for many years. It is important to take a
developmental history and to get corroborating information to
piece together the life history. It is important to recognize that the
patient may have developed complicating syndromes over time
such as depression, substance abuse, or dementia but that the
original hoarding condition may have begun in isolation. The
mental status examination should be largely normal unless there are
comorbidities. Rigidity, inflexible thinking, and lack of insight are
common. Given the high level of co-occurring mood and anxiety
disorders, differentiating the conditions may be mostly academic.
It is important to be certain that the hoarding is not the result of a
psychotic disorder or secondary to apathy and anergy related to
depression. Additionally, some neurodevelopmental disorders
result in hoarding behavior. Additionally, hoarding disorder is not
diagnosed if the behavior appears to be directly related to
obsessions or compulsions from OCD. Usually, the hoarding is
very specific in OCD and is distressing to the patient.
MANAGEMENT
First, it is critical to understand that the hoarding behavior has been
an emotionally stabilizing and regulating system for the patient. So,
suddenly disturbing the pattern could be extremely distressing and
could result in complications such as panic attacks or self-
destructive or violent acts. Approach the patient with compassion
and understanding. Begin with listening and hearing his or her view
of the accumulated things. Any steps to clean out or throw things
away should be done cautiously with support. Engaging the patient
in small beginning actions can help to overcome the patient’s fears.
However, the prognosis is poor for many patients who have been
hoarding for decades, and steps may need to be taken toward
guardianship or conservatorship if the patient lacks insight and
cannot keep safe. Medications can be helpful to treat emergent or
comorbid anxiety or depressive symptoms.
TRICHOTILLOMANIA
Trichotillomania is characterized by recurrent pulling out of hair on
various parts of the body, particularly the head and eyebrows. The
hair pulling must cause significant distress, and repeated attempts
to stop must have failed.
EPIDEMIOLOGY
Trichotillomania affects 1% to 2% of the general population and is
overwhelmingly seen in females (10:1 ratio).
ETIOLOGY
The etiology is not known. It is more likely to occur in patients
with a first-degree relative with OCD.

The patient usually has a history of hair pulling beginning in early
adulthood, just after onset of menarche or puberty in males. It often
waxes and wanes with periods of abstinence and then relapses
sometimes associated with hormonal changes or stress. The hair
pulling often involves visible regions of the head and face but can
involve pubic or axillary hair as well. The mental status
examination should be normal if there are no comorbid psychiatric
conditions.
It is critical to rule out inflammatory or allergic conditions that can
result in involuntary hair loss as well as obsessive, psychotic, or
neurodevelopmental problems that result in the person perceiving
that it is best to pull or eliminate hair.
MANAGEMENT
Management is largely with behavioral habit reversal training
and/or CBT. There is a limited role for medications, but some
patients benefit from SSRIs, clomipramine, or a low dosage of an
antipsychotic medication.
EXCORIATION DISORDER
Excoriation disorder is characterized by recurrent skin picking that
leads to visible skin damage and that is not the result of a skin
problem or another cause. The patient must be unable to stop skin
picking despite trying.
EPIDEMIOLOGY
The lifetime prevalence is 1.4% or more. The female to male ratio
is 3:1. Onset is usually around puberty with a chronic course.
ETIOLOGY
The etiology is unknown, but the disorder is related to OCD.

The history and mental status will reveal a pattern of ongoing skin
picking and excoriation that interferes with work and social life.
The skin picking is caused by a strong desire to pick and not based
on the belief that one has an infection or other reasons for skin
picking.
The differential diagnosis includes actual skin infections (e.g., with
scabies, delusional parasitosis, Prader-Willi syndrome, and other
OCD-related conditions).
MANAGEMENT
Although not proven, SSRI medications and CBT and related
therapies may be of use. Atypical antipsychotics might be used to
augment antidepressant effects or on suspicion of a delusional
component. The glutamate modulating medication N-acetylcysteine
has also shown some promise in treating this condition.
KEY POINTS
OCD is a distressing condition characterized by
recurrent obsessions and compulsions.
OCD is treated with CBT, clomipramine, SSRIs,
systematic desensitization, flooding, and response
prevention.
Body dysmorphic disorder is seen in families with
OCD and is best treated with CBT and SSRI
medication.
Hoarding disorder is often diagnosed late and is
difficult to treat.
Trichotillomania is seen more frequently in families
with OCD and responds to habit reversal therapy
and sometimes SSRIs or clomipramine.
CLINICAL VIGNETTES
VIGNETTE 1
A 51-year-old woman with a long-standing diagnosis of obsessive-
compulsive disorder (OCD) describes her symptoms to you. She
reports recurrent intrusive thoughts that her apartment is going to be
destroyed by fire or water damage. As a result of these thoughts, she
used to spend approximately 6 hours a day checking to make sure the
stove, iron, and bathroom fan are turned off. She also checked under
both the bathroom and kitchen sinks to make sure that there was no
water leak. She reports that since beginning treatment with
fluvoxamine approximately 5 years ago, she now spends less than 2
hours per day engaged in these repetitive checking behaviors.
1. Which of the following neurotransmitters has been most strongly

implicated as a mediator of obsessive thinking and compulsive
behaviors?
a. Dopamine
b. Norepinephrine
c. Glutamate
d. Serotonin
e. γ-Aminobutyric acid (GABA)
2. The neural structures most strongly implicated in the

development of OCD include:
a. Anterior insula and dorsal anterior cingulate cortex
b. Posterior parietal and posterior occipital cortices
c. Ventral striatum and ventral tegmental area
d. Prefrontal cortex, dorsal anterior cingulate cortex, caudate, and
amygdala
ANSWERS
1. Answer D:
OCD is one of the more disabling and potentially chronic anxiety
disorders. It is characterized by anxiety-provoking intrusive thoughts
and repetitive behaviors. Obsessions may consist of aggressive
thoughts and impulses, fears of contamination by germs or dirt, or
fears of harm befalling someone. Compulsions such as washing,
checking, or counting are rituals with the purpose of neutralizing or
reversing the fears. Functional imaging studies over the past several
years have implicated prefrontal cortex, cingulate gyrus, and basal
ganglia (especially caudate nucleus) dysfunction in the pathogenesis
of this disorder. Serotonin is also believed to play a primary role in
OCD. Selective serotonin reuptake inhibitors, such as fluvoxamine,
are first-line treatment for OCD. Dopamine may play a role in
depression and some antidepressant agents, such as bupropion, may
modify the dopaminergic system. Dopamine, however, has been most
strongly implicated in the pathogenesis and treatment of
schizophrenia and in substance use disorders. Norepinephrine has a
prominent role in the pathogenesis of major depression and other
psychiatric conditions. Glutamate dysregulation has been implicated in
many conditions, including schizophrenia. GABA dysfunction is most
strongly implicated in anxiety disorders, and GABA agonists are
widely used to treat some anxiety disorders.
2. Answer D:
OCD has been linked to altered function in prefrontal regions (medial
and lateral orbitofrontal cortices), the dorsal anterior cingulate cortex,
the caudate nucleus, and the amygdala. The caudate nucleus has
been linked with habit formation, and this role may be relevant to
repetitive actions in OCD. Anterior insula and dorsal anterior cingulate
cortex are prominent structures in the brain’s salience network.
Posterior parietal and posterior occipital cortices have prominent roles
in visual perception. The ventral striatum and ventral tegmental area
have key roles in reward behavior and reinforcement learning.
Eating disorders are characterized by disturbances in eating
behaviors and/or an irrational perspective of body image or size.
These disorders are classified into six distinct diagnoses in the
Diagnostic and Statistical Manual of Mental Disorders, Fifth
edition (DSM-5); however, many of their symptoms overlap. A
significant diagnostic distinction is based on ideal body weight.
When abnormal eating behavior causes significantly low body
weight, a diagnosis of anorexia nervosa is strongly considered. If
body weight is maintained in the presence of abnormal eating
behaviors, bulimia nervosa and binge-eating disorder are potential
diagnoses. Another crucial diagnostic marker is the presence of
compensatory behaviors such as purging and overexercising. This
aspect helps delineate between bulimia nervosa and binge-eating
disorder. Eating disorders likely lie along a continuum of
disturbances in eating behavior and often are almost always
associated with mood disorders and other psychiatric illnesses
(Table 7-1).
NEURAL BASIS
Although the different types of eating disorders do not share a
single neurobiologic origin, serotonergic dysfunction is strongly
associated with these conditions and associated symptoms.
Alterations in dopamine, norepinephrine, neuropeptide, and opiate
systems are also implicated. Hypothalamic and limbic neural
regions, including the reward system, likely play a role. High
comorbidity with obsessive-compulsive disorder and body image
disturbances (body dysmorphic disorder) suggests overlap with
brain regions affected in these conditions. Regions mediating
feeding behavior, such as nucleus accumbens, orbitofrontal cortex,
and insula, are also likely affected.
TABLE 7-1. Classification of Eating Disorders

Diagnosis Anorexia Bulimia Nervosa Binge-Eating
Nervosa Disorder
Types Restricting No subtypes No subtypes
type
Binge-
eating/purging
type
Stage In partial In partial remission In partial
remission In full remission remission
In full In full remission
remission
Severity Based on Based on frequency of Based on number
body mass inappropriate of binge-eating
index compensatory episodes per week
behaviors
ANOREXIA NERVOSA
Anorexia nervosa is a severe eating disorder characterized by
significantly low body weight. This means that the body weight is
below what would be minimally expected for the individual. The
weight loss must result from intentional restriction of nutrition.
EPIDEMIOLOGY
The point prevalence of anorexia nervosa is approximately 0.4%
among young women, and more than 90% of patients with anorexia
nervosa are women. The prevalence in men remains unclear. Onset
usually occurs in adolescence or young adulthood and is often
associated with a stressful event. The disorder is rare before
puberty or after age 40. Anorexia nervosa is more common in
industrialized societies and among individuals of higher
socioeconomic classes.
ETIOLOGY
Eating disorders and their subtypes likely share many common
bases of origin. Psychological theories of anorexia nervosa remain
speculative. Patients with anorexia nervosa generally have a high
fear of losing control, difficulty with self-esteem, and commonly
display “all-or-none” thinking. Although it is not specific to eating
disorders, past physical or sexual abuse may be a risk factor.
Contemporary theories focus on the need to control one’s body.
Social theories propose that societal opinions, which equate low
body weight with attractiveness, drive individuals to develop eating
disorders. Although this fact may be responsible for some cases
(e.g., anorexia nervosa is more common among dancers and
models), historically, anorexia nervosa has been present during
periods when societal mores for beauty were different.
Biologic, familial, and genetic data support a biologic and
heritable basis for anorexia. Family studies reveal an increased
incidence of mood disorders and anorexia nervosa in first-degree
relatives of patients with anorexia nervosa. Twin studies show
substantially higher concordance for monozygotic versus dizygotic
twins. Neuroendocrine evidence supporting a biologic contribution
to anorexia includes alterations in corticotropin-releasing factor,
reduced central nervous system norepinephrine metabolism, and
that amenorrhea (caused by decreased luteinizing hormone and
follicle-stimulating hormone release) sometimes precedes the onset
of anorexia nervosa.

DSM-5 criteria for the diagnosis of anorexia nervosa include
nutrition restriction leading to significantly low body weight, either
an intense fear of weight gain or persistent behavior that prevents
weight gain, and an irrational perception of one’s body
weight/shape, allowing body shape to overly impact their sense of
self, or poor insight into the seriousness of their low body weight.
Patients with anorexia nervosa generally do not have a loss of
appetite; they refuse to eat out of fear of gaining weight.
Amenorrhea in postmenarchal women is a good malnutrition
marker, but is not diagnostic of the disorder.
Individuals with anorexia nervosa commonly overexercise to
reduce weight and alter body shape. Some restrict energy intake as
a primary method of weight control; others use binge eating or
purging (use of laxatives, enemas, diuretics, or induced vomiting).
The behavioral repertoire used to control body weight is used to
classify anorexia nervosa further into two mutually exclusive
subtypes: restricting type and binge-eating/purging type. In the
restricting type, weight loss is due to food restriction and/or
excessive exercise without binge-eating or purging episodes. In the
binge-eating/purging type, the individual has engaged in binge
eating or purging recurrently over the past 3 months.
The natural course of anorexia is not well understood. Some
individuals recover after one episode, others waver with relapse
and remission, but some become persistent and chronic. The crude
mortality rate of anorexia nervosa is 5% per decade. Deaths are
usually secondary to suicide or medical complications from the
illness, especially cardiac conditions. Ongoing suicide risk
assessment should be part of the individual’s treatment plan.
Conditions resembling anorexia should be ruled out. These include
major depression with loss of appetite and weight, some psychotic
disorders in which nutrition may not be adequate, body dysmorphic
disorder, and a variety of general medical (especially
neuroendocrine) conditions. Anorexia nervosa is differentiated
from bulimia nervosa primarily by the presence of significantly low
weight in individuals with the former.
MANAGEMENT
The management of anorexia nervosa is initially directed at the
presenting symptoms. When medical complications are present,
these must be carefully treated and followed up. During starvation,
psychotherapy is of little value because of the cognitive impairment
produced by starvation. When patients are less medically ill, a
therapeutic program including supervised meals; weight and
electrolyte monitoring; psychoeducation about the illness,
starvation, and nutrition; individual psychotherapy, and family
therapy can begin. The most efficacious treatments for the disorder
are family-based treatment and adolescent-focused treatment.
Psychotropic medications have little or no effect on anorexia per
se, but are used to treat comorbid psychiatric illness. Using
antidepressants for individuals with comorbid mood or anxious
conditions is common.
BULIMIA NERVOSA
Bulimia nervosa is an eating disorder characterized by binge-
eating epsisodes followed by recurrent compensatory behaviors
(e.g., purging, laxative misuse, fasting) to prevent weight gain.
EPIDEMIOLOGY
The yearly prevalence of bulimia nervosa is 1% to 1.5% in young
women and the male-to-female ratio is 1:10. The disorder peaks in
late adolescence and early adulthood. This illness occurs with
similar frequency across industrialized countries.
ETIOLOGY
Many of the factors in the genesis of anorexia nervosa are also
implicated in bulimia nervosa. Familial and genetic studies support
similar familial linkages in both disorders. Psychological theories
for bulimia nervosa stress an addiction or obsessive-compulsive
behavioral model. Biologic, neurologic, and endocrine findings are
less prominent in theories of causation of bulimia nervosa.
Abnormal serotonin metabolism is thought to play more of a role in
bulimia nervosa than in anorexia nervosa. Still, as many as 15% of
individuals with bulimia nervosa will crossover or fluctuate with
anorexia nervosa or binge-eating disorder. The current symptoms
will guide the diagnosis.

Bulimia nervosa is diagnosed in individuals who engage in binge-
eating and compensatory behaviors but maintain at least low-
normal body weight. As with some individuals with anorexia
nervosa, their self-evaluation is overly influenced by their body
weight and shape.
Food binges in bulimia nervosa may be precipitated by stress or
altered mood states. Once a binge begins, the individual typically
feels out of control and continues to eat large quantities of food,
often to the point of physical discomfort. Purging may follow and
most often consists of vomiting, usually induced mechanically by
stimulating the gag reflex. Other purging methods include misusing
laxatives, diuretics, and enemas. Individuals with bulimia nervosa
often exercise and restrict their food intake.
Bulimia nervosa should be distinguished from the binge-eating and
purging subtype of anorexia nervosa as well as binge-eating
disorder. If body weight is significantly less than minimal, a
diagnosis of anorexia nervosa should be considered, instead. Binge
eating can occur with major depression and in borderline
personality disorder, but it is not tied to a compulsion to reduce
weight.
MANAGEMENT
The treatment for bulimia nervosa is similar to that for anorexia
nervosa. Although medical complications of starvation are not
present, other medical complications can require careful medical
management and, at times, hospitalization. For example, electrolyte
imbalance due to purging can be an emergent problem
necessitating immediate intervention. Psychotherapy focuses at
first on achieving control of eating behavior. Cognitive therapy
may be useful in treating overconcern with body image. Self-
esteem and interpersonal relationships become the focus of therapy
as the behavioral problems abate. Antidepressants, especially
selective serotonin reuptake inhibitors such as fluoxetine, treat
bulimia nervosa more effectively than they treat anorexia nervosa
(including patients who do not have comorbid depression).
BINGE-EATING DISORDER
Binge-eating disorder is characterized by binge-eating episodes
without compensatory behaviors (e.g., purging, laxative misuse,
fasting).
EPIDEMIOLOGY
The yearly prevalence of binge-eating disorder among women and
men in the United States is 1.6% and 0.8%, respectively. For
women, the disorder appears to be equally prevalent between racial
and ethnic groups.
ETIOLOGY
Although little is known about the development of the disorder, it
is common among adolescents and young adults. The disorder
begins commonly in adolescence and early adulthood. It appears to
have an as-yet unknown genetic component because it runs in
families. There are no well-defined biologic, neurologic, or other
somatic theories with regard to the causation of the disorder.
Unlike bulimia nervosa, individuals with binge-eating disorder are
unlikely to experience crossover to other eating disorders. Impulse
control dysfunction is thought to be an underlying mechanism for
binge-eating disorder. This may be one reason stimulant
medication has been effective in the treatment of the disorder.

Binge-eating disorder is found in individuals who experience
binge-eating episodes but do not engage in compensatory
behaviors. They are typically normal-weight to obese individuals
and may have recently begun dieting. Obesity is not
pathognomonic for the disorder because the majority of obese
individuals do not engage in binge eating. The type of food
consumed in a binge is unique to each individual and the
environment.
The individual’s binge-eating episodes must contain at least
three specific characteristics. These include eating more rapidly
than normal, eating until uncomfortably full, eating large amounts
when not hungry, feeling embarrassed due to the amount eaten, or
feeling disgusted/depressed/guilty afterward. In addition, the
individual must be distressed by the behavior. They are self-
conscious about their binges and attempt to conceal this behavior.
Triggers for the episodes are variable and can include life stressors,
derogatory thoughts about their body image, and boredom.
Binge-eating disorder should not be confused with the other eating
disorders. The presence of compensatory behaviors would suggest
a diagnosis of bulimia nervosa and significantly low body weight
entertains a diagnosis of anorexia nervosa. One of the driving
forces behind identifying binge-eating disorder from the other
eating disorders is the treatment plan. Stimulant medication should
be avoided in persons with anorexia nervosa and bulimia.
Differentiating binge-eating disorder from a manic or hypomanic
state is also important for treatment planning purposes. Binge-
eating disorder is more responsive to treatment than the other
eating disorders.
MANAGEMENT
The treatment for binge-eating disorder is different from that for
anorexia nervosa or bulimia nervosa. Rarely do individuals need a
level of care beyond outpatient services. Medical complications are
much less common than those associated with the other eating
disorders because of the lack of compensatory behaviors.
Maintaining a normal, healthy weight is important for short- and
long-term health. Psychotherapy, as with bulimia nervosa, focuses
on obtaining control over the binge behaviors. Improving self-
worth and eradicating negative self-concepts are important avenues
of intervention. Cognitive and behavioral interventions are utilized
to improve how the individual processes personal experience and
controls behavior. Psychostimulants can be directly helpful with
binge-eating disorder. Other psychotropic medication may also
alleviate comorbid depressive and anxious symptoms.
MEDICAL COMPLICATIONS
Chronic eating disorders can have serious medical consequences
both with and without treatment. Table 7-2 lists the common
medical complications of eating disorders. The most serious of
these, gastric or esophageal rupture and cardiac arrhythmias
secondary to electrolyte imbalance (particularly hypokalemia as a
result of recurrent purging), can be fatal. Other complications of
eating disorders parallel those of chronic medical illness, take a
severe toll on the patient’s overall functioning, and cause
tremendous suffering and burden for their families.
TABLE 7-2. Medical Complications of Eating Disorders

Behavior Medical Complication
Binge Gastric dilatation or rupture
eating Obesity
Vomiting Esophageal rupture
Parotiditis with hyperamylasemia
Hypokalemic, hypochloremic, metabolic alkalosis (with
cardiac arrhythmias)
Ipecac (an emetic) toxicity (cardiac and skeletal myopathies)
Laxative Constipation (caused by laxative dependence)
use Metabolic acidosis
Dehydration
Diuretic Electrolyte abnormalities (with cardiac arrhythmias)
use Dehydration
Starvation Leukopenia, anemia
Increased ventricular/brain ratio
Hypotension, bradycardia
Hypothermia
Hypercholesterolemia
Edema
Dry skin, lanugo (fine hair)
Treatment of severely underweight (less than 75% ideal body

weight) patients with anorexia can lead to refeeding syndrome: a
state caused by sudden carbohydrate intake severely depleting body
phosphate stores (hypophosphatemia) resulting in rhabdomyolysis,
delirium, seizures, and eventual cardiovascular collapse. Looking
for signs of edema, congestive heart failure, and mental status
changes are important during refeeding. Gradual refeeding with
monitoring of serum potassium and phosphate can prevent the
complication. In addition to these medical complications,
secondary psychiatric and neurologic sequellae include cognitive
decline, metabolic encephalopathy, and severe mood disturbance,
all with profound consequences for patients and their families.
Binge-eating disorder is associated with an increased risk of
weight gain and obesity. Because of the lack of compensatory
behaviors, there are significantly fewer medical complications than
with anorexia nervosa or bulimia nervosa. Still, owing to the
emotional factors experienced by individuals with binge-eating
disorder, the risk of depression and anxiety is increased.
PREVENTION
Focus on preventing mental illness has led to research on
interventions that might decrease the incidence or severity of eating
disorders.
A number of modifiable risk factors for eating disorders have
been identified, including familial focus on weight and appearance,
presence of mood or anxiety disorder, life transitions, certain
athletic or entertainment professions, and the influence of media
portrayals of body type. One study has shown that providing a
cognitive therapy–oriented educational module to at-risk young
women decreased the incidence of eating disorders over a 5-year
follow-up period.
KEY POINTS
Anorexia nervosa is characterized by restriction of
nutrition, leading to significantly low body weight,
fear of gaining weight, body image distortion, and
persistent lack of insight into the seriousness of
the condition.
Anorexia nervosa is diagnosed more than 90% of
the time in women.
Anorexia nervosa can cause serious medical
complications, including refeeding syndrome, and
has a crude mortality rate of 5% per decade.
Bulimia nervosa is a severe eating disorder
characterized by binge eating and purging.
Bulimia nervosa is also characterized by
maintenance of at least low-normal body weight.
Bulimia nervosa is more common in women than
in men by a ratio of 10:1.
Bulimia nervosa can have serious medical
complications including electrolyte imbalance and
esophageal rupture.
Binge-eating disorder is a significant eating
disorder characterized by episodes of binge eating
associated with a negative self-concept but
without compensatory behaviors.
Binge-eating disorder is twice as prevalent in
women as in men.
Binge-eating disorder can be treated with
psychostimulants and psychotherapy.
CLINICAL VIGNETTES
VIGNETTE 1
A 22-year-old woman with a prior diagnosis of bulimia nervosa
presents to the emergency room during her college exam period with
an irregular heartbeat. The patient is weighed and found to be at her
ideal weight. She has tried cognitive-behavioral therapy for bulimia in
the past and found it helpful but has not been in therapy in the past
year. The patient is evasive when queried, but denies recent attempts
at purging behavior or use of laxatives. On examination, the patient is
noted to have a callus on the second joint of the right index finger. The
electrocardiogram (EKG) demonstrates ST-segment depression with
flattening of the T waves and development of U waves.
1. What is the most likely finding?
a. Hypokalemia
b. Hyperkalemia
c. Hypercalcemia
d. Hypocalcemia
e. Esophageal rupture
2. Once the patient is medically stabilized and her hypokalemia has

been treated, she is referred to the eating disorders outpatient
program for further treatment. At her intake, she asks about
medication therapy for bulimia nervosa. The most appropriate
initial medication choice is:
a. Olanzapine
b. Haloperidol
c. Fluoxetine
d. Amitriptyline
ANSWERS
1. Answer A:
Bulimia nervosa is an eating disorder characterized by binge-eating
episodes followed by recurrent compensatory behaviors (e.g., purging,
laxative misuse, fasting) to prevent weight gain. The patient is likely
purging by inducing vomiting mechanically with her right index finger
which produces the evidence of a callus on her finger. Loss of gastric
fluids produces a secondary metabolic acidosis, eventually leading to
potassium loss via the kidney. Hypokalemia can produce life-
threatening arrhythmias and is detectable on the EKG as ST-segment
depression with flattening of the T waves and development of U
waves. Esophageal rupture is also a possible complication of induced
vomiting but there is no indication of this finding from the provided
history. Patients with bulimia nervosa may be overweight or maintain
near-normal body weights.
2. Answer C:
Fluoxetine is a selective serotonin reuptake inhibitor antidepressant
that has demonstrated efficacy in the treatment of bulimia nervosa.
Olanzapine is an atypical antipsychotic with a common side effect of
appetite stimulation and weight gain and so would be relatively
contraindicated in a patient with weight and body image concerns.
Haloperidol is a typical antipsychotic that is not a first-line treatment
for bulimia. Amitriptyline is a tricyclic antidepressant that may impact
bulimic behavior and depressed mood (if present) in bulimia but would
be relatively contraindicated because of its risk for inducing cardiac
arrhythmia in a patient with a history of vomiting-induced hypokalemia.
Many common psychiatric disorders, including anxiety, mood, and
psychotic disorders, manifest symptoms during childhood and
adolescence. In addition, there is a group of disorders usually first
diagnosed in children. The Diagnostic and Statistical Manual of
Mental Disorders, 4th edition (DSM-IV) classified these disorders
under the title of Disorders of Childhood and Adolescence. The
DSM-5 moved away from classification based on age of onset to a
lifespan approach. Within each chapter, disorders are arranged in a
chronologic order reflecting the age of onset and pattern of
diagnoses. Conditions that have their onset in the developmental
period are classified under neurodevelopmental disorders. This
chapter reviews the most prominent and clinically relevant
neurodevelopmental disorders and discusses other key diagnoses
that are relevant to child and adolescent psychiatry (Table 8-1).
TABLE 8-1. Neurodevelopmental Disorders and Child and

Adolescent Psychiatric Conditions
Neurodevelopmental Disorders
Intellectual disabilities
Intellectual development disorder
Global developmental delaya
Communication disorders
Language disorder
Speech sound disorder
Childhood-onset fluency disorder (stuttering)a
Social (pragmatic) communication disorder
Autism spectrum disorder
Attention-deficit hyperactivity disorder
Specific learning disorder
Motor disorders
Developmental coordination disordera
Stereotypic movement disordera
Tic disorders: Tourette’s disorder
Child and Adolescent Psychiatric Conditions
Anxiety disorders
Separation anxiety disorder
Childhood feeding and eating disorders
Pica
Rumination disorder
Feeding disorder of infancy or early childhood
Elimination disorders
Encopresis
Enuresis
Gender dysphoria
Disruptive, impulse control, and conduct disorders
Conduct disorder
Oppositional defiant disorder
Depressive disorders
Major depressive disorder
Disruptive mood dysregulation disorder
Bipolar disorders
Bipolar disorder
Trauma- and stressor-related disorders
Posttraumatic stress disorder
Neurocognitive disorders
Pediatric delirium
aDisorder listed in DSM-5 but not reviewed here.
INTERVIEWS AND ASSESSMENTS WITH
CHILDREN AND ADOLESCENTS
Assessment in child and adolescent psychiatry is multifaceted and
requires attention to stage of development, normative age-
appropriate behavior, family structure and dynamics, and
functioning in various settings including home and school. Table 8-
2 outlines developmental milestones in the social, motor, and
language domains. Knowledge of appropriate milestones can be
used to screen for abnormal psychomotor development, which can
be a sign of psychiatric disorders.
TABLE 8-2. Developmental Milestones

Gross Fine Language Cognitive/Social/Adaptive
Motor Motor
3 Raises Pointing Coos, Recognizes parent,
months chest/head motions at vocalizes anticipates feeding
in prone objects reciprocally
position,
rolls prone
to supine
6 Sits Reaches Babbles Attached to primary
months unsupported with one caregiver
hand, rakes
with all
fingers
9 Pulls to Rotates Understands Stranger anxiety, plays
months standing hand when “no,” imitates peek-a-boo (gesture games)
grasping sounds (“da-
object da,” “ma-ma”)
12 Walks Voluntarily Uses one to Imitates, cooperates with
months releases four words, dressing
items, understands
makes command with
scribble gesture
marks
18 Walks Builds Combines two Names pictures, plays near
months upstairs, three-block words, points other children
throws a tower to body parts
ball, runs
2 years Jumps with Uses fork Vocabulary of Removes simple clothing,
two feet, and spoon, 50–300 words, parallel play
kicks ball builds uses two- to
seven-to three-word
eight-block phrases
tower
3 years Alternates Copies Uses five- to Knows name/age/gender,
feet on circle eight-word understands
stairs sentences, cold/tired/hungry
75% of
language is
understandable
to strangers
4 years Balances on Tells a Puts on shoes, Washes and dries hands
one foot story, language is
Catches a copies recognizable
ball 100% of a
square
5 years Skips with Draws a Asks meaning Names four colors,
alternating person of words understands and abides by
feet with six rules, cooperative play
body parts,
copies a
triangle
Adapted from Marino B, Fine K. Blueprints Pediatrics, 5th ed. Philadelphia, PA: Lippincott, Williams &
Wilkins, 2009, T4-1. McMillan JA, De Angelis CD, Feigin RD, et al. Oski's Pediatrics: Principles & Practice
4th ed. Philadelphia, PA: Lippincott Williams & Wilkins, T96-1, T96-2.
Children, especially young children, usually express emotion in

a more concrete (less abstract) way than adults. Consequently,
child interviews may require more concrete queries (“Do you feel
like crying?” instead of, “Are you sad?”). Playing games, drawing,
taking turns in telling stories, and imaginative play are often used
to gain insight into the child’s emotional and interpersonal life.
During play, observations are also made regarding activity level,
motor skills, and verbal expression. Children are more likely than
adults to have comorbid mental disorders, making diagnosis and
treatment more complicated. Consulting with parents and obtaining
information from schools, teachers, and other involved parties (e.g.,
Department of Social Services/Youth Services) are essential to
proper assessment.
The complexities of diagnosis in child psychiatry often require
the use of psychological testing. Tests of general intelligence
include the Stanford-Binet Intelligence Scale (one of the first
intelligence tests developed and often used in young children) and
the Wechsler Intelligence Scale for Children–Revised (WISC-R).
The WISC-R is the most widely used intelligence test for assessing
school-age children. It yields a verbal score, a performance score,
and a full-scale score (both verbal and performance) or intelligence
quotient (IQ). The Autism Diagnostic Observational Schedule is
used to establish a diagnosis of autism spectrum disorder (ASD).
There are many other tests and objective rating scales designed to
measure behavior (e.g., impulsiveness, physical activity),
perceptual-motor skills (by drawing people, placing pegs in
appropriately shaped holes), and personality style (by describing
what is happening in an ambiguous scene).
Because seizure activity or subtle electroencephalographic
abnormalities are common in certain child psychiatric disorders, an
electroencephalogram (EEG) may be warranted. The evaluation of
neurodevelopmental disorders usually involves a search for
possible genetic or medical causes as well.
NEURODEVELOPMENTAL DISORDERS
INTELLECTUAL DISABILITY (INTELLECTUAL

DEVELOPMENT DISORDER)
Patients with intellectual disability have deficits in both intellectual
functions (reasoning, judgment, abstract thinking, academics,
problem solving, and learning from experience) and adaptive
functioning that do not meet appropriate developmental and
sociocultural standards. Severity ranges from mild to profound and
is based on adaptive functioning as defined on three domains—
conceptual, social, and practical. Federal law has replaced the use
of the term mental retardation with intellectual disability.
Epidemiology
Intellectual disability affects 1% of the population and has a male-
to-female ratio of 1.6:1 for mild and 1.2:1 for severe forms.
Etiology
Intellectual disabilities can be thought of as a final common
pathway of a number of childhood or perinatal disorders. These
could include genetic or chromosomal abnormalities such as Down
syndrome (trisomy 21, the most common cause of intellectual
disability) or fragile X syndrome (the most common heritable
cause). Overall, there are more than 500 genetic abnormalities
associated with intellectual disabilities. Other etiologies of
intellectual disability include inborn errors of metabolism, perinatal
or early childhood head injuries, maternal diabetes, substance
abuse, toxemia, and exposure to teratogens or infections such as
rubella. In 30% to 40% of patients with intellectual disability, no
clear etiology can be determined.
Clinical Manifestations
History, Physical and Mental Status Examinations, and Laboratory Tests
As a neurodevelopmental disorder, the onset of symptoms must be
during the developmental period (before age 18). Patients must
have concurrent deficits and impairments in both intellectual
abilities and one domain of adaptive functioning. Laboratory
findings may suggest metabolic or chromosomal etiology. Most
children with intellectual disabilities have physical malformations
that identify them at birth as being at risk (such as the characteristic
facies of the child with Down syndrome). Even infants can show
signs of significantly sub-average intellectual functioning,
identified by parents or providers, after failure to meet
developmental milestones in a number of functional areas (e.g.,
delayed speech, social skills, or self-care skills capacity) or low
scores on standardized psychometric tests of intelligence like the
Stanford-Binet (usually only for very young children) or WISC-R
(standard for school-age children).
Attention-deficit/hyperactivity disorder (ADHD), learning
disorders, autism, depression, schizophrenia, and seizure disorders
can all resemble intellectual disabilities in presentation. These
disorders can also be comorbid conditions. A thorough medical and
neurologic evaluation, including psychoeducational testing, an
EEG, and brain imaging (computed tomography or magnetic
resonance imaging) are often indicated.
Management
Management depends on the degree of disability, the course, and
the particular abilities of the child and the parents. Growth and
development occur in children with intellectual disabilities in
patterns similar to typically developing children, but at a slower
rate. They can have developmental spurts, like typically developing
children that could not have been predicted at an earlier age.
In mild intellectual disabilities, children often require support
with education to meet age-related expectations. Children with
mild disabilities can usually learn to read, write, and perform
simple arithmetic. With family support and special education, most
of these children will be able to live with their parents. The long-
term goal of treatment is to help children to achieve mainstream
social and occupational milestones.
In moderate intellectual disabilities, training can help children
learn personal care skills. Children can learn to talk, to recognize
his or her name and a few simple words, and to perform activities
of daily living (bathing, dressing, handling small change) without
assistance. The long-term goal of treatment is typically to enable
the child to live and function in a minimally supervised setting with
their family or a group home.
Children with severe or profound intellectual disability almost
invariably require care in institutional settings, usually beginning
very early in life. These forms are often associated with specific
syndromes (e.g., Tay-Sachs’s disease) in which there is progressive
physical deterioration leading to premature death.
COMMUNICATION DISORDERS
Communication disorders involve deficits in language, speech, and
communication. The DSM-5 lists four main communication
disorders: language disorder, speech sound disorder, childhood-
onset fluency disorder (stuttering), and social (pragmatic)
communication disorder. These involve problems with
communication that are significant when controlled for age and
cause impairment in academic or social functioning.
ETIOLOGY
Communication disorders tend to run in families. The exact
etiology is unknown, but they are hypothesized to be related to
neurodevelopmental defects.
EPIDEMIOLOGY
Up to 5% of school age children are estimated to have
communication disorders. Frequent comorbidity occurs. For
example, expressive language deficits may be present along with
speech sound disorder, whereas ADHD, behavioral problems, and
specific learning disorders may be present in those with social
(pragmatic) communication disorder or language disorder.
Language disorder presents as difficulties in understanding or using
language because of problems with vocabulary, sentence structure,
and discourse. It might involve either expressive language,
receptive language, or both. Because development of language can
be variable in the preschool age, a valid diagnosis can be made
only after about 4 years of age.
Speech disorders are problems with the motor production of
sounds. They could be difficulties with phonology (learning speech
sounds) and articulation or stuttering (frequent repetition and
prolonging of sounds). By 3 years of age, most speech should be
easy to understand and problems are frequently noticed after that
point.
Social (pragmatic) communication disorder consists of
problems with understanding the rules of verbal and nonverbal
communication. This is similar to ASD but without restrictive or
repetitive patterns of behavior.
Diagnosis is made by speech and language testing and when
other comorbid conditions do not explain the symptoms.
Hearing and other sensory impairments and normal variations in
development can be frequently confused with communication
disorders. For problems with speech, structural and neurologic
deficits like cleft palate or dysarthria should be ruled out. The
differential diagnosis includes intellectual disability, ASD, and
selective mutism as well.
MANAGEMENT
Speech disorders usually respond well to speech therapy. Receptive
language issues or the presence of specific learning disorder has a
poorer prognosis.
AUTISM SPECTRUM DISORDER

ASD is a common pervasive developmental disorder of childhood
onset. It is characterized by deficits in two domains: impaired
social communication and interactions, and a repetitive or restricted
repertoire of activities and interests. A major change with DSM-5 is
folding several different disorders from DSM-IV into the ASD,
with severity levels of 1 (“requiring support”), 2 (“requiring
substantial support”), and 3 (“requiring very substantial support”).
ETIOLOGY
Autistic disorder is familial. A known genetic mutation may be
associated with autism in about 15% of patients; however, genetic
studies demonstrate incomplete penetrance (36% concordance rate
in monozygotic twins). A small percentage of those with autistic
disorder have fragile X disorder, and a high rate of autism exists in
patients with tuberous sclerosis.
EPIDEMIOLOGY
Over the past few decades, estimates for prevalence of ASD have
shown an increase from 2 to 5 children per 10,000 live births to
about 60 children per 10,000 live births. Causes for this increase
are unknown, but are hypothesized to be in part due to increased
diagnosis and awareness. The male-to-female ratio is 3 to 4:1.
History, Mental Status Examination, and Laboratory

Tests
Abnormal development is usually first noted soon after birth.
Commonly, the first sign is impairment in social interactions
(failure to develop a social smile, facial expressions, or eye-to-eye
gaze in the first 6 months) or delayed language development over
the first 2 years. Older children often fail to develop nonverbal
forms of communication (e.g., body postures and gestures) and
may seem to have no desire or to lack the skills to form friendships.
There is also a lack of seeking to share enjoyment (i.e., not
showing, sharing, or pointing out objects they find interesting). By
definition, findings must be present in the early developmental
period.
Autistic disorder is also characterized by a marked impairment
in communication. There may be delay in or total lack of language
development. Those children who do develop language show
impairment in the ability to initiate and sustain conversations and
use repetitive or idiosyncratic language. Language may also be
abnormal in pitch, intonation, rate, rhythm, or stress.
Finally, there are usually restrictive, repetitive, or stereotyped
patterns of behavior, interests, or activities. There may be an
encompassing preoccupation with one or more stereotyped and
restricted patterns of interest (e.g., amassing baseball trivia), an
inflexible adherence to specific nonfunctional routines or rituals
(e.g., eating the same meal in the same place at the same time each
day), stereotyped or repetitive motor mannerisms (e.g., whole-body
rocking or spinning objects), and a persistent preoccupation with
the parts of objects (e.g., buttons, or focusing only on the wheels of
a toy car).
Approximately 38% of children with autistic disorder have
comorbid seizures; approximately 40% have intellectual disability.
EEGs and intelligence testing are typically part of the initial
evaluation. Rarely, specific special skills are present (e.g., calendar
calculation).
Intellectual disability, ADHD, childhood psychosis, language
disorders, and congenital deafness or blindness should all be ruled
out. Frequent comorbidity with other childhood psychiatric and
neurodevelopmental disorders occurs (up to 70% of children with
autism have one other co-occurring childhood disorder).
MANAGEMENT
Autistic disorder is a chronic lifelong disorder. The level of
severity is based on the support needed for the impairment on the
two psychopathologic domains. This can widely vary from one end
of the spectrum to the other. Individuals with what was previously
diagnosed as Asperger’s syndrome may be high functioning and
may require only little support (level 1), whereas those with
intellectual disability or language impairment may require more
support (level 2 or 3). Parents will often have to learn behavioral
management techniques designed to reduce the impairments from
rigid and stereotyped behaviors to improve social functioning.
Many children with autism require special education or specialized
day programs for behavior management.
Children with autism with a comorbid seizure disorder are
treated with anticonvulsants. No medications have been shown to
help with the core symptoms on the two domains; however, the use
of atypical neuroleptics (risperidone and aripiprazole), approved by
the U.S. Food and Drug Administration, has been found to be
helpful for aggression and irritability. Other medications are used
“off label” for treating comorbid symptoms, but typically have
lower efficacy and higher side-effect rates than when used in
typically developing children.
ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER
ADHD is characterized by a persistent and dysfunctional pattern of
overactivity, impulsiveness, inattention, and distractibility.
ETIOLOGY
The disorder runs in families and cosegregates with mood
disorders, substance use disorders, learning disorders, and
antisocial personality disorder. Families with a child diagnosed
with ADHD are more likely than those without an offspring with
ADHD to have family members with the previously mentioned
disorders.
The etiology of the disorder is unknown, but perinatal injury,
malnutrition, and substance exposure have all been implicated.
Many children with ADHD have abnormalities of sleep
architecture (decreased rapid eye movement latency, increased
delta latency), EEG, and soft neurologic signs. Brain imaging
studies indicate that overall brain volume is smaller in children
diagnosed with ADHD when compared with controls.
EPIDEMIOLOGY
The prevalence of ADHD in school-age children is estimated to be
5%. The boy–girl ratio ranges from 2:1 to 4:1 in the general
population to 9:1 in clinical settings. Boys are much more likely
than girls to be brought to medical attention.

Tests
Diagnosis of ADHD can be made at any age, but to meet criteria
for ADHD, there must be evidence of several inattentive or
hyperactive symptoms before age 12; symptoms must also be
present in two or more settings (e.g., school, home). Symptoms that
occur in only one setting suggest an environmental or
behavioral/psychodynamic cause.
Preschool-age children are usually brought for evaluation when
they are unmanageable at home. Typically, they stay up late, wake
up early, and spend most of their waking hours in various
hyperactive and impulsive activities. Children with a great deal of
hyperactivity may seem to constantly run around the house, cause
damage, and wreak havoc.
When these children enter school, their difficulties with
attention become more obvious. They appear not to follow
directions, forget important school supplies, fail to complete
homework or in-class assignments, and attempt to blurt out
answers to teachers’ questions before being called on. Because of
their inattention and hyperactivity, these children often become
known as troublemakers. They often fall behind their peers
academically and socially.
Evaluation of the child involves gathering a careful history
from parents and teachers (the latter usually through report cards
and written reports). The child’s behavior with and without the
parent is carefully observed during psychiatric assessment.
Informal testing is carried out by having the child attempt to
complete a simple puzzle, write the letters of the alphabet,
distinguish right from left, and recognize letters traced on the palms
(graphesthesia). Physical examination, particularly focusing on
neurologic function, is imperative. No specific laboratory tests are
helpful in making the diagnosis. Psychoeducational testing can help
understand the strengths and vulnerable areas of a child’s
developmental presentation.
It is important to distinguish symptoms of ADHD from age-
appropriate behaviors in active children (running about, being
noisy, etc.). Children can appear inattentive if they have learning or
language disorders and the environment is over- or
understimulating. Psychoeducational testing and careful evaluation
of the school program can help clarify the diagnosis.
Emotional dysregulation present in ADHD must also be
differentiated from an underlying mood disorder. Children with
disruptive mood dysregulation disorder, in addition to
distractibility and poor attention, will exhibit inappropriately
intense outbursts that are persistent.
Children with oppositional defiant disorder (ODD) may resist
work or school tasks because of an unwillingness to comply with
others’ demands but not out of difficulty in attention.
Children with other psychiatric disorders (e.g., major
depressive disorder [MDD] or bipolar disorder) can also exhibit
features of inattention, but are characterized by other symptoms
that may not be accounted for by ADHD alone. A careful
psychosocial history can also help rule out symptoms consistent
with early childhood or trauma or other anxiety disorders like
separation anxiety.
Symptoms that resemble ADHD can also occur as a side effect
of a medication (e.g., bronchodilators or activation and akathisia
from selective serotonin reuptake inhibitors (SSRIs) or a psychotic
or pervasive developmental disorder; these children are not
considered to have ADHD. ADHD may be comorbid with any of
the previously mentioned disorders, but dual diagnosis should be
made only when it is needed to explain the full clinical picture.
MANAGEMENT
The management of ADHD involves a combination of somatic and
behavioral treatments. In younger children, first-line treatment is
behavior therapy only. Behavioral management techniques include
positive reinforcement, firm limit setting, and techniques for
reducing stimulation (e.g., one playmate at a time; short, focused
tasks). In those who do not respond to behavior therapy, or older
children with more significant impairments, most respond
favorably to psychostimulants. Methylphenidate is the first-line
agent, followed by d-amphetamine. Clinicians try to use the
smallest effective dose and to restrict use to periods of greatest
need (i.e., the school day) because psychostimulants have long-
term physical effects (decrease in appetite leading to weight loss
and inhibited body growth). α-2 Receptor agonists like clonidine
and guanfacine can also be used either in addition to a stimulant or
by themselves if stimulants are not tolerated. Some children can be
treated effectively with atomoxetine (Strattera), a selective
norepinephrine reuptake transporter inhibitor. This medication
blocks the norepinephrine reuptake transporters throughout the
brain. In the frontal lobe, where there are few dopamine reuptake
transporters, dopamine is normally cleared by the norepinephrine
reuptake transporter, so that blocking this transporter with
atomoxetine leads to an increase in dopamine. Some other
antidepressants that alter dopamine and norepinephrine have shown
efficacy in ADHD, like bupropion (Wellbutrin).
SPECIFIC LEARNING DISORDER

Learning disorders are characterized by performance in a specific
area of learning substantially below the expectation of a child’s
chronologic age, measured intelligence, and age-appropriate
education. The DSM-5 identifies three specifiers: impairments in
reading, written expression, or mathematics.
ETIOLOGY
Specific learning disorders often occur in families. They are
presumed to result from focal cerebral injury or from a neurologic
developmental defect. Prematurity and exposure to nicotine are risk
factors.
EPIDEMIOLOGY
Learning disorders are relatively common, occurring in 5% to 15%
of school age children and 4% of adults. The incidence of disorder
of written expression is not yet known. Learning disorders are two
to three times more common in boys than in girls.

Tests
Specific learning disorders are typically diagnosed after a child has
exhibited difficulties in a specific academic area. Because reading
and math are usually not taught before kindergarten, the diagnosis
is seldom made in preschoolers. Some children may not be
diagnosed until fourth or fifth grade, particularly if they have a
high IQ and can mask their deficits. The diagnosis of learning
disorder is confirmed through specific intelligence and
achievement testing. Children with learning disorders do not obtain
achievement test scores consistent with their overall IQ.
It is important to establish that a low achievement score is not
caused by some other factor such as lack of opportunity to learn,
poor teaching, or cultural factors (e.g., English as a second
language). Physical factors (such as hearing or vision impairment)
must also be ruled out.
Finally, it is important to consider and test for more global
disorders such as pervasive developmental disorder, intellectual
disability, and communication disorders. It is common to find that
several of these disorders coexist. A specific learning disorder
diagnosis is made when the full clinical picture is not adequately
explained by other comorbid conditions.
MANAGEMENT
Children with these disorders often need remedial or specialized
education. They also need to be taught learning strategies to
overcome their particular deficits. Acceptable skills in the
disordered area can often be achieved with steady supportive
educational assistance, although patients may be affected by these
disorders throughout adulthood.
MOTOR DISORDERS
TIC DISORDERS: TOURETTE’S DISORDER

Tourette’s disorder is a rare disorder in which the child
demonstrates multiple involuntary motor and vocal tics for more
than 1 year, starting before the age of 18. A tic is a sudden, rapid,
recurrent, nonrhythmic, stereotyped motor movement or
vocalization.
Etiology
Tourette’s disorder is highly familial and appears to frequently co-
occur with obsessive-compulsive disorder. Despite evidence of
genetic transmission in some families, no gene (or genes) has yet
been discovered to explain the etiology of the disorder.
Epidemiology
Tourette’s disorder affects 0.3% of the population. There is a 2 to
4:1 male–female ratio.
History, Mental Status, and Physical Examinations
The patient or family usually describes an onset in childhood or
early adolescence before age 18. Vocal tics are usually loud grunts
or barks, but can involve shouting words; the words are sometimes
obscenities (coprolalia). The patient describes being aware of
shouting the words, being able to exert some control over them, but
being overwhelmed by an uncontrollable urge to say them. Motor
tics can involve facial grimacing, tongue protrusion, blinking,
snorting, or larger movements of the extremities or whole body.
Motor tics typically antedate vocal tics; barks or grunts typically
antedate verbal shouts. The motor tics are not painful.
A careful neurologic evaluation should be performed to rule out
other causes of tics. Wilson’s disease and Huntington’s disease are
the principal differential diagnostic disorders. An EEG should be
performed to rule out a seizure disorder. Careful evaluation for
other comorbid psychiatric illnesses should be performed.
Stimulants used to treat other psychiatric disorders may unmask
tics.
Management
Treatment for mild or moderate tics involves psychoeducation and
psychotherapy. Education describing etiology and prognosis
(improving with age) to parents, patients, teachers, and caregivers
can help out all at least. Psychotherapies such as habit reversal
therapy help patients learn techniques to minimize tics. Treatment
for more severe tics typically involves the use of low doses of high-
potency neuroleptics such as haloperidol or pimozide, but various
other agents are used. The child and his or her family should
receive education and supportive psychotherapy aimed at
minimizing the negative social consequences (e.g., embarrassment,
shame, isolation) that occur with this disorder.
CHILD AND ADOLESCENT PSYCHIATRIC

CONDITIONS
ANXIETY DISORDERS
Separation Anxiety Disorder

Separation anxiety is seen in children below the age of 3
manifesting as fear or distress when separated from attachment
figures. It is considered to be a part of normal development for
children in this age group and usually goes away with formation of
secure attachments. In separation anxiety disorder, the distress is
out of proportion to that expected for the developmental level and
causes functional impairment. Age of onset is around the preschool
time period but can manifest at any time during childhood.
Prevalence in children is estimated to be around 4%. It can
sometimes be related to an environmental stressor such as the loss
of a family member, pet, or a move to a different setting.
Symptoms may include school avoidance, fears or concerns about
parents, or anxiety about loved ones getting hurt. Differential
diagnosis should include other anxiety disorders, agoraphobia, and
depression. Cognitive behavioral therapy (CBT) is the treatment of
choice for separation anxiety disorder.
Social Anxiety Disorder

Social anxiety involves the fear of being judged negatively by
others in social situations. Social situations cause fear or anxiety in
excess of what is expected for the context. Symptoms must be
present for at least 6 months for a diagnosis of social anxiety
disorder. In children, social anxiety may present as a fear of
situations at school. Children with social anxiety may avoid
performances or speaking in front of class, playing with other
children, and be afraid of getting bullied. Social anxiety is thought
to affect children and adults at the same rate, with the estimated
prevalence being about 7%, but symptoms typically present after
elementary school. A number of biologic (heredity, temperament,
autonomic reactivity, anxiety sensitivity) and environmental
(attachment style, parenting, peer, and social problems) factors
have been implicated in the etiology. If untreated during childhood,
social anxiety persists into adult life. Treatment usually involves
exposure-based CBT and use of medications such as SSRIs for
severe symptoms.
CHILDHOOD FEEDING AND EATING DISORDERS
Pica
Pica is a condition characterized by the developmentally
inappropriate ingestion of nonnutritive substances for a period of at
least 1 month, when the ingestion of nonnutritive substances is not
part of a culturally sanctioned behavior. Little is known about the
etiology and epidemiology of pica. In those patients with
intellectual disability, rates of pica increase with increasing
severity. Medical complications such as lead poisoning,
gastrointestinal complications, and infectious consequences may
result. The disorder may be sustained or self-limited. DSM-5 lists
pica in the section on “Feeding and Eating Disorders”; and while it
was previously considered a disorder of childhood, onset in adults
has been described as well.
Rumination Disorder
Rumination disorder is a feeding disorder characterized by repeated
regurgitation of ingested food for at least 1 month after a period of
normal eating. The regurgitative behavior cannot be caused by
gastrointestinal difficulties or another eating disorder such as
bulimia nervosa. The condition is rare and is most commonly
diagnosed in infants, but it may appear at a later age in patients
with intellectual disability. Regurgitated food may be expelled or
rechewed and swallowed. If regurgitation is severe and insufficient
calories are ingested, malnutrition can occur. Mortality rates may
approach 25%. Spontaneous remission is common. The etiology is
unknown.
Feeding Disorder of Infancy or Early Childhood

Feeding disorder is characterized by continued failure to eat
enough food, leading to weight loss or failure to gain weight and
lasting at least 1 month. The condition cannot be the result of a
general medical condition. Associated conditions such as those
resulting from malnutrition with impaired sleep, irritability, and
developmental delays may occur. The etiology is unclear but
impaired caregiver–child interactions may play a role.
ELIMINATION DISORDERS
Encopresis
The diagnostic criteria for encopresis require repeated episodes (at
least once per month for at least 3 months) of defecation in
inappropriate places in individuals at least 4 years old or having an
equivalent developmental level. The inappropriate defecation
cannot be caused by another medical condition or drug, with the
exception of constipation. About 1% of 5-year-olds display
encopresis. When present, encopresis is classified according to
whether or not there is constipation with overflow incontinence.
Enuresis
The diagnostic criteria for enuresis require repeated episodes (two
times per week for at least 3 consecutive months or the presence of
significant distress) of urination into one’s clothes or bed in
children at least 5 years old or having an equivalent developmental
level. The inappropriate urination cannot be the result of a general
medical condition or substance. Enuresis is classified according to
the time of day of occurrence as nocturnal only, diurnal only, or
nocturnal and diurnal. Roughly 7% of 5-year-old boys have
enuresis. The prevalence is about 3% in 5-year-old girls.
GENDER DYSPHORIA
Gender dysphoria in the DSM-5 has been updated from “Gender
Identity Disorder” in the DSM-IV. This new name reflects a focus
on the affective state of the patient, rather than the patient’s identity
as the primary issue. The diagnostic criteria focus on a patient’s
preference for a gender other than one assigned at birth. Diagnoses
are defined by age of onset, “Gender Dysphoria in Children” and
“Gender Dysphoria in Adolescents and Adults.” Prevalence
estimates vary widely between countries and vary by age. Early
studies observed more natal males than natal females referred to
gender clinics in Canada and the Netherlands, while more recent
studies have found a predominance of natal females. Formal
epidemiologic studies are still lacking.
While the evidence for most treatments for gender dysphoria is
not well established, the American Academy of Child and
Adolescent Psychiatry has established nine principles for the care
of gay, lesbian and transgender youth. These principles include a
complete diagnostic evaluation of psychosexual development, the
need for confidentiality, the exploration of family dynamics,
enquiry about increased psychiatric risk factors, the aim to foster
healthy psychosexual development, that there is no evidence that
sexual orientation can be altered by therapy, that clinician should
be aware of the current state of evidence, that clinicians should be
prepared to act as a liaison to schools and community agencies, and
that clinicians should be aware of community resources for this
population.
DISRUPTIVE, IMPULSE CONTROL AND CONDUCT
DISORDERS
Conduct Disorder
Conduct disorder is defined as a repetitive and persistent pattern of
behavior in which the basic rights of others or important age-
appropriate societal norms or rules are violated. Disordered
behaviors include aggression toward people or animals, destruction
of property, deceitfulness, theft, or serious violations of rules
(school truancy, running away). Conduct disorder is the childhood
equivalent of adult antisocial personality disorder. Prevalence
estimates range from 2% to 10%, and it is frequently seen
comorbid with ADHD or learning disorders. Adoption studies
show a genetic predisposition, but psychosocial factors play a
major role. Parental separation or divorce, parental substance
abuse, severely poor or inconsistent parenting, and association with
a delinquent peer group have been shown to influence the
development of conduct disorder.
Treatment involves individual and family therapy. Some
children may need to be removed from the home and placed in
foster care. Parents who retain custody of a child with conduct
disorder are taught limit setting, consistency, and other behavioral
techniques. Medications are used only to treat a comorbid ADHD
or mood disorder, but not for the conduct disorder itself. The long-
term outcome depends on the severity of the disorder and the
degree and type of comorbidity. Of children with conduct disorder,
25% to 40% go on to have adult antisocial personality disorder.
Oppositional Defiant Disorder

ODD is diagnosed in a child with a pattern of argumentative or
defiant behavior, angry mood, and vindictiveness. The frequency of
the behavior significantly exceeds that of other children his or her
mental age (or is less tolerated in the child’s particular culture).
This behavior causes distress in family or in social contexts.
Development of these behaviors is hypothesized to be a product of
temperament along with environmental factors. ODD is mostly
commonly comorbid with ADHD and less commonly with anxiety
disorders. Children diagnosed with ODD are at a higher risk of
developing conduct disorder. Management emphasizes individual
and family counseling and treating comorbid conditions.
DEPRESSIVE DISORDERS
Major Depressive Disorder

Diagnosis of MDD in children and adolescents is made on the basis
of the same criteria used for adults. MDD tends to be clustered in
families. A proposed etiology is thought to be due to the interaction
of genetic vulnerability with stressors and the child’s cognitive and
coping skills. Prevalence is about 2% in children and 4% to 8% in
adolescents. A large number of children may also have sub-
syndromal symptoms. The clinical presentation of MDD may vary
from adults depending on developmental stage. Children may not
be able to talk about their symptoms and tend to exhibit more
irritability, somatic symptoms, tantrums, and poor frustration
tolerance. MDD can be frequently comorbid with other anxiety
disorders, ADHD, and substance use disorders (especially in
adolescents). Suicidal thoughts and behavior are the symptoms of
greatest concern, and risk is greater if there is a history of previous
attempts, presence of other comorbid disorders, aggression, access
to firearms, history of trauma, and a family history of suicide.
Treatment for mild and uncomplicated depression is education
and support. For some moderate episodes, psychotherapy may be
indicated. CBT is the psychotherapy modality with the most
evidence of benefit and is followed by interpersonal psychotherapy.
However, other psychotherapies have been effective in randomized
trials as well, including psychodynamic psychotherapy. For
moderate to severe depressive illnesses, treatment with
antidepressants may be indicated with SSRIs as the first-line
agents. Large-scale randomized control trials like the Treatment of
Adolescents with Depression Study (TADS) have demonstrated
that a combination of CBT with medication might be most
beneficial for remission in symptoms. Fluoxetine and escitalopram
are the only two medications approved by the FDA for treatment of
MDD in adolescents. Management of comorbid conditions is vital.
Disruptive Mood Dysregulation Disorder

Disruptive mood dysregulation disorder (DMDD) is a new
diagnosis included in the DSM-5 with the aim of minimizing the
wrongful diagnosis of bipolar disorder in children with pervasive
and chronic irritability. Although persistent irritability was
previously classified under bipolar disorder in the DSM-IV, only
those children with symptoms of typical manic or hypomanic
episodes are currently considered to have bipolar disorder. Criteria
for DMDD includes severe and recurrent outbursts (starting before
10 years of age), which can be either verbal or physical aggression,
that happen at least three times per week and are present every day
for at least 12 months. Children with DMDD have outbursts in
multiple settings including home and school. No accurate
prevalence estimates are currently available. Because irritability
may be a common symptom in children, other disorders have to be
first ruled out including ODD, ADHD, MDD, bipolar, ASD, and
intermittent explosive disorder. Treatments are also not clearly
defined yet for this newly defined disorder, but psychological
interventions and medications that have been effective in other
disorders with irritability and tantrums, such as ADHD, anxiety,
depression, and bipolar disorder, may be considered.
BIPOLAR DISORDERS
Similar to MDD, criteria for bipolar disorders I and II are the same
for adults and children. However, significant controversy exists in a
narrow versus broad interpretation of the criteria. Bipolar I disorder
requires the presence of an episode of mania;whereas in bipolar II
disorder, criteria need to be met for a hypomanic episode. In
children and adolescents, significant comorbidity occurs with
externalizing disorders such as ADHD, ODD, conduct disorder,
and alcohol or substance use. Heritability is thought to be high,
with nearly half of children having a first-degree relative with
bipolar disorder. Medication is first line for treatment of bipolar
disorder, with four medications being approved for mania treatment
in the adolescent age group (lithium, olanzapine, risperidone, and
aripiprazole). Other anticonvulsants such as valproic acid and
lamotrigine are also frequently used. Psychoeducation is important
to help patient and family.
TRAUMA- AND STRESSOR-RELATED DISORDERS:

POSTTRAUMATIC STRESS DISORDER
Children may be exposed to a wide variety of trauma, including
abuse, violence, natural disasters and community violence. The
DSM criteria for PTSD for children older than 6 years of age are
similar to that for adults and include exposure to traumatic events
and the triad of reexperience (in the form of recurrent memories,
dreams, or distressing flashbacks), avoidance (of stimuli associated
with trauma), and issues with arousal (outbursts, reactivity,
hypervigilance, sleep, and concentration issues). There may be
difficulties with mood and cognition as well. Trauma (child abuse,
domestic violence) during the developmental period may also
cause attachment disruption. Complex trauma and other adverse
childhood experiences have been shown to increase the risk for
psychiatric disorders such as anxiety and depression, besides also
increasing the risk for medical problems such as hypertension,
diabetes, and even cancer. Frequent comorbidities are anxiety,
depression, behavioral problems, complex bereavement disorder,
and substance use disorders. Symptoms of depersonalization
(feeling of detachment from one’s own body) and derealization
(feeling like the world is unreal) can occur and may be mistaken
for psychotic symptoms. A number of evidence-based
psychotherapeutic treatments are available, including trauma-
focused CBT.
NEUROCOGNITIVE DISORDERS: PEDIATRIC DELIRIUM

Although delirium in the hospitalized adult patient is frequently
diagnosed, the understanding and recognition of delirium in
children and adolescents has greatly expanded in the past two
decades. Delirium is characterized by disturbances in
consciousness, attention, and cognition, with a characteristic
waxing and waning course. There are three subtypes: hyperactive,
hypoactive, and mixed, depending on the psychomotor
presentation. Diagnosis is difficult in pediatric patients because
symptoms may be more subtle and can include inconsolability,
purposeless actions, and autonomic dysregulation. A number of
factors including toxic, metabolic, infectious, and iatrogenic causes
have been implicated in delirium. Long-term effects are unknown
for pediatric patients, but in adults delirium is associated with
increased morbidity and mortality. Treatment may include
nonpharmacologic measures (cognitive stimulation, reorientation,
sleep cycle stabilization, avoidance of certain medication) and
pharmacologic agents (usually a low dose of an antipsychotic
medication).
KEY POINTS
The DSM-5 uses a more lifespan approach and
created a new chapter for neurodevelopmental
disorders.
The neurodevelopmental disorders are frequently
comorbid. For example, many patients with ADHD
might have a specific learning disorder and some
patients with ASD have an intellectual disability.
Intellectual disability can be classified on the basis
of severity ranges mild to profound, and is based
on adaptive functioning as defined on three
domains—conceptual, social, and practical.
The DSM-5 lists four main communication
disorders: language disorder, speech sound
disorder, childhood-onset fluency disorder
(stuttering), and social (pragmatic) communication
disorder.
A major change with DSM-5 is folding several
different disorders from DSM-IV into the ASD, with
severity levels of 1 (“requiring support”), 2
(“requiring substantial support”), and 3 (“requiring
very substantial support”).
ADHD is more common in boys (4:1) and is
characterized by inattentiveness and hyperactivity
occurring in multiple settings.
For a diagnosis of ADHD, other causes of
inattentiveness or hyperactivity must be ruled out,
and symptoms must be present before age 12.
Social anxiety disorder and separation anxiety
disorder are commonly seen in the pediatric
population.
Conduct disorder is the childhood equivalent of
adult antisocial personality disorder.
ODD can be a precursor to conduct disorder.
There are three types of feeding and eating
disorders of infancy or early childhood: pica
(developmentally inappropriate eating of
nonnutritive substances), rumination disorder
(repeated regurgitation of ingested food), and
feeding disorder (failure to eat enough to maintain
or gain weight in the absence of other medical
causes).
There are two types of elimination disorders:
encopresis (repeated episodes of inappropriate
defecating) and enuresis (repeated episodes of
inappropriate urination).
Depression, bipolar disorder, and DMDD are seen
in children.
CLINICAL VIGNETTES
VIGNETTE 1
Jackson is a 10-year-old boy with autism who has been having daily
tantrums. Although he has a history of difficulty following directions
and only can speak in two- to three-word sentences, this new behavior
has been worsening over the last 2 weeks. He was born full term and
had delayed gross and fine motor movement, delayed independent
toileting, and delayed speech. He attends his local public school and
is in special education classes where he typically can sit still for 15-
minute lessons and can go for several days without a temper tantrum.
1. Average intelligence in children with autism is:

a. Above average
b. Average
c. Below Average
2. Children can typically speak in two- to three-word sentences by

age:
a. 18 months
b. 3 years
c. 5 years
d. 7 years
3. Which complication would typically NOT be on the differential

diagnosis in this case:
a. Medication side effect
b. Bladder infection
c. Dyslexia
d. Change in environment
4. Which medication is FDA approved for irritability associated with

autism in children:
a. Risperidone
b. Citalopram
c. Methylphenidate
d. Guanfacine
5. Average brain size in patients with autism compared with normal

controls is:
a. Larger in the first 2 years of life, same in adulthood
b. Same in the first 2 years of life, larger in adulthood
c. No difference throughout the life span
VIGNETTE 2
Sophia is a 12-year-old girl with difficulty paying attention, failing
grades, and emotional breakdowns every Sunday night. She excels in
athletics and is sociable with peers. Her parents have been divorced
for 3 years, and she splits time evenly between the two households,
changing each week. She was born full term and with no
complications. As a child, Anna was distractible, often jumping from
topic to topic and was physically hyperactive. She did not have trouble
in preschool or elementary school and received average grades until
middle school, when she began having trouble keeping track of her
work and missing assignments. Her parents report that when she
prepared to change houses each Sunday night, she often broke down
in tears.
1. The estimated prevalence of attention-deficit/hyperactivity

disorder (ADHD) in children and adolescents in the United States
is:
a. 1%
b. 5%
c. 10%
d. 15%
2. First-line pharmacologic treatment for ADHD is which class of

medications:
a. Stimulants
b. Selective serotonin reuptake inhibitors (SSRIs)
c. α-Agonists
d. Atypical antipsychotic medications
3. The most common comorbidity in children with ADHD is:

a. Anxiety disorders
b. Mood disorders
c. Autism spectrum disorders (ASDs)
d. Oppositional defiant disorder (ODD)
4. Cortical gray matter thickness is increased in patients with ADHD.

a. True
b. False
VIGNETTE 3
Emma is a 13-year-old girl having difficulty in eighth grade. She
started the school year off well, but quickly began to have difficulties
socially and academically. Her parents report that she is “not
interested” in spending time with her friends, and she recently quit the
math Olympiad team. Her grades, which had been A’s in seventh
grade, are now mostly B’s and C’s, often because of missed
assignments. When her teachers asked her about her work, she
shrugged and replied, “I just didn’t get it done, I guess.” She has
missed several days of school, with no explanation of where she has
been or what she has been doing. She has lost 10 lb during the fall
semester, but says she “wasn’t trying to.” Emma denies suicidal
thoughts, but her friends have written to her parents with their
concerns.
1. Emma’s most accurate diagnosis is:

a. ADHD
b. General anxiety disorder
c. Major depressive disorder (MDD)
d. Obsessive-compulsive disorder (OCD)
e. Substance abuse disorder
2. Which of these conditions is most commonly comorbid with

Emma’s symptoms?
a. ADHD
b. Disruptive behavior disorder
c. Anxiety spectrum disorders
d. ODD
e. Substance abuse disorder
3. The FDA-approved medication for the treatment of depression in

adolescents is:
a. Aripiprazole
b. Buspirone
c. Fluoxetine
d. Sertraline
e. Paroxetine
4. The risk factor that confers the greatest risk for a suicide attempt
for an adolescent is:
a. Previous suicide attempt
b. Presence of comorbid disorders
c. Availability of lethal agents
d. Exposure to negative events (violence, sexual abuse)
e. Family history of suicides
5. Which of these characteristics makes an adolescent with

depression more likely to develop bipolar disorder?
a. Comorbid substance use
b. Family history of anxiety
c. Depression without psychosis
d. Comorbid conduct disorder
e. Medication-induced mania or hypomania
VIGNETTE 4
Aiden is a 15-year-old boy who presented to the clinic with refusal to
attend school. He recently started the 10th grade and reports being
intensely fearful of school, especially his English class, which has a
public performance component in this grade. He has been having
nightmares about standing up in class to read a poem out loud,
though he admits to having memorized it. He says he wakes up every
night anticipating bullying and being made fun of by classmates,
though he admits that it has not happened yet. He has not been to
school in 2 weeks. His mother reports that these 2 weeks have been
“a huge relief” and Aiden has been sleeping well, has been pleasant
during the day, and their daily fights over school refusal have
disappeared. Aiden reports that he wants to have friends and attend
school, but he would rather be home schooled now, to see if it will “go
away.”
1. Which of these diagnoses are Aiden’s symptoms most consistent
with?
a. Separation anxiety disorder (SAD)
b. MDD
c. Specific phobia
d. Social anxiety disorder
e. Generalized anxiety disorder
2. The mean age of onset of social anxiety disorder is:

a. 2
b. 6
c. 13
d. 20
e. 25
3. Which of the following medications is FDA approved for treatment

of social anxiety disorder in children and adolescents?
a. Escitalopram
b. Lorazepam
c. Fluoxetine
d. Guanfacine
e. None of the above
4. The treatment of choice for Aiden is:

a. Dialectical behavior therapy
b. Interpersonal psychotherapy
c. Cognitive-behavioral therapy (CBT) with social skills training
d. Psychodynamic psychotherapy
e. Rational emotive behavior therapy
ANSWERS
1. Answer C:
Like children without autism, children with autism have a range of
intellectual capabilities. When studied as a large group, children with
autism have lower intelligence scores than their peers without autism.
Estimates for comorbid intellectual disability range from 25% to 75% in
children with autism, with one recent large cohort study finding the
rate to be 42.6%. In a study of 156 children with ASDs, the average
intelligence quotient (IQ) was 75.5, compared with the mean IQ for all
children of 100. In that study, the investigators looked at the pattern of
intellectual capabilities and disabilities in children with autism. Over
the last several decades, some researchers have proposed a typical
pattern of performance IQ (higher) versus verbal IQ (lower) mismatch
in children with autism. This pattern was not supported by this study
and needs further investigation.
2. Answer B:
Expressive language develops gradually in children from the minute
they are born through adolescence. In the first few months of life,
children begin to verbalize with cooing and crying. During this time,
they usually develop a social smile and by 6 months they may chuckle
and giggle. By 1 year, children may use speech and other sounds to
get attention of caregivers. At 1 year, they may use one or two words
like hi, dog, dada, or mama. During the second year of life, children
develop speech at a rapid rate, seemingly adding words every week.
They may develop one- or two-word questions (“where’s baba?”)
during this year and begin to be able to ask for things like “more milk.”
By 3 years, children can typically use two- to three-word sentences to
talk about and ask about things. By age 4, they will have words for
most things that they encounter on a daily basis and their speech is
understood by people who know them well. By age 5, most people
can understand children even if they have never met them and
children gain more mastery of language, learning how to rhyme, use
pronouns, pluralize words, and answering questions. By age 6,
children may still struggle with some harder sounds like l, s, r, v, z,
and others, but continue to advance in ability to keep a conversation
going, telling a story, and talking without repeating sounds and words
as often.
3. Answer C:
When examining a child with intellectual disability, providers should
keep a broad differential in mind for acute changes in mental status or
behavioral functioning. Stressors such as medication side effects,
bladder infections, or changes in environment (starting and ending
school, changing caregiver, etc.) can affect a child’s behavior without
prominent physical symptoms. These examples can cause a change
in behavior over 1 to 2 weeks, but something like dyslexia typically
presents with behavioral change in a more gradual, developmental
pattern.
4. Answer A:
Risperidone and aripiprazole are FDA approved for irritability
associated with autism. Citalopram, methylphenidate, and guanfacine
are often used to treat symptoms in children with autism, but they are
not FDA approved for this indication. Guanfacine and methylphenidate
are both FDA approved for use in ADHD for children older than 6
years of age.
5. Answer A:
Children with autism appear to exhibit a different growth pattern in
brain volume than their age-matched peers. Several studies have
noted that brain size in patients with autism is slightly reduced at birth,
increases in size so that it is enlarged compared with controls in the
first 2 years of life and then the growth slows so that by adulthood the
two populations have similar brain sizes.
1. Answer B:
ADHD is one of the most common disorders in child and adolescent
psychiatry. Recognized for decades, there has been debate about the
prevalence and whether it is increasing over time. A large meta-
analysis found the prevalence rate to be roughly 5% and unchanged
over three decades, with changes from study to study more due to
methodological differences than a change in underlying prevalence.
2. Answer A:
First-line pharmacologic treatment for ADHD in children and
adolescents aged 6 to 18 is the class of stimulants that include
methylphenidate and the mixed amphetamine salts. SSRIs are used
primarily for the treatment of anxiety and depression in children. The
SSRIs fluoxetine and escitalopram are FDA approved for use in
depression in children. Duloxetine, a mixed serotonin–norepinephrine
reuptake inhibitor (SNRI), is FDA approved for use in generalized
anxiety disorder in children and adolescents. α-Agonists, such as
guanfacine and clonidine, are FDA approved for use in ADHD in
children and adolescents, but are considered second-line treatments
compared with stimulants. Atypical antipsychotics such as risperidone
have shown effectiveness in trials as adjunctive treatment for
treatment-resistant ADHD, but are not considered first-line
monotherapy interventions for ADHD in children.
3. Answer D:
According to the DSM-5, ODD is comorbid with ADHD in roughly half
of children with the combined presentation and in one quarter of those
with the inattentive presentation. Several studies have looked at
subgroups of comorbidities with ADHD. While ODD is the most
common comorbidity, anxiety disorders, mood disorders, and ASDs
have significant comorbidities with ADHD, and providers should pay
close attention to the detection of these other disorders, as their
presence or absence can affect treatment planning and prognosis.
There is some evidence that children with ADHD + anxiety had slightly
better treatment outcomes than those without anxiety, and better than
those with comorbid ODD.
4. Answer B:
ADHD is typically considered a disorder of executive functioning.
Decreased ability to focus and to avoid distraction and poor planning
are common symptom presentations in ADHD. These behaviors have
been most closely linked to disordered functioning in the prefrontal
cortex (PFC) and striatum. In examining the size and thickness of
different brain regions, total gray matter thickness has been noted to
be reduced in patients with ADHD compared with controls, with the
biggest differences seen in the PFC.
1. Answer C:
To meet a diagnosis of MDD, adolescents need to have five (or more)
of the nine following symptoms for a 2-week period: depressed mood,
loss of interest or pleasure, significant weight loss (when not dieting)
or weight gain, fatigue or loss of energy, feeling of worthlessness or
excessive guilt, increase or decrease in sleep, observable
psychomotor agitation or retardation, decreased concentration, and
recurrent thoughts of dying or suicidal ideations. Of these symptoms,
one of either depressed mood or losses of interest need to be
definitely present. Symptoms need to cause significant impairment in
functioning and cannot be due to substance use or other medical
conditions. Emma seems to meet criteria for MDD. Although it seems
some of her symptoms could be explained by generalized anxiety
disorder (somatic complaints) or ADHD (decrease in grades, which
could be due to a loss of concentration), there are no other symptoms
consistent with these diagnoses. There are also no obsessions,
compulsive behavior, or any reported history of substance use.
2. Answer C:
Up to 40% to 90% of adolescents with depressive disorders have
other comorbid psychiatric disorders. Among these, it is estimated that
50% have more than two comorbid disorders. Of these conditions,
anxiety disorders are the most frequently comorbid followed by
disruptive behavior, ADHD, and substance use disorder in
adolescents. The onset of a depressive disorder is usually after onset
of an anxiety spectrum disorder. Having a depressive disorder places
adolescents at a higher risk for developing conduct or substance use
disorders.
3. Answer C:
There are only two FDA-approved medications for the treatment of
depression in adolescents. They are both SSRIs. The SSRI fluoxetine
is approved for children ages 8 and older and the SSRI escitalopram
is approved for children ages 12 and older. However, other SSRI
antidepressants like sertraline and citalopram are also frequently
used. Evidence for use of SSRIs is somewhat mixed with response
rates for SSRIs only slightly higher than placebo. Buspirone, a
serotonin 1A agonist, is frequently used for treatment of anxiety;
however, there is not strong evidence to support efficacy in children
and adolescents. Paroxetine is a shorter-acting SSRI that has a
withdrawal syndrome and hence is not used in this population. While
aripiprazole, an atypical antipsychotic, can sometimes be used for
augmentation of antidepressant effects, it should not be used for first-
line treatment of depression.
4. Answer A:
History of a previous suicide attempt confers the greatest risk for
future suicide attempt. All other factors including comorbid psychiatric
disorders, impulsivity and aggression, availability of lethal agents,
exposure to negative events, and family history of suicidal behavior
lead to increased risk for suicide attempts. Both suicidal ideation and
attempts are quite common in adolescents with about 60% of those
with MDD having had suicidal ideations and about 30% having had
attempts. Suicide is the third leading cause of death among all youth
and young adults in the United States. When compared with adults,
however, suicide rates are lesser. The suicide rate for those less than
20 years old is roughly 3 per 100,000 per year. The rate for the
general population is 13.26 per 100,000 per year.
5. Answer E:
About 20% to 40% of adolescents with depression are thought to
develop bipolar disorder. It is important to differentiate between
symptoms of major depression from those of the depressive phase of
bipolar disorder. Children and adolescents are at a greater risk for
developing manic symptoms when treated with antidepressants. The
other risk factors in addition to antidepressant-induced symptoms
include having a family history of bipolar disorder, history of subclinical
manic or hypomanic symptoms, presence of psychosis, and
depression with psychosis. However, it is important to note that some
children who receive an antidepressant may become “activated” and
may not be at a higher risk for developing bipolar disorder.
1. Answer D:
Patients with social anxiety disorder have an intense and debilitating
fear of social situations that last for at least 6 months or more. The
fear is described as being inconsistent with the social situation.
Anxiety needs to be present in more than one social setting. In
children, social anxiety can frequently present as school avoidance.
Fear of being embarrassed or being humiliated in front of others will
be a common concern. School refusal may also be a part of SAD;
however, in SAD there is persistent anxiety about losing primary
attachment figures for at least 4 weeks. There can be symptoms even
when adult has to leave the house. There are usually no difficulties in
social situations. There are no symptoms consistent with MDD in the
above example. Generalized anxiety disorder can be distinguished by
anxiety about multiple different situations or activities (lasting for more
than 6 months). There are multiple physical symptoms that are
typically present including restlessness, low energy, irritability, muscle
tension, or insomnia. Specific phobia is anxiety that is related to one
specific object or situation and does not usually include social
embarrassment.
2. Answer C:
13. Seventy-five percent of patients with social anxiety disorder are
diagnosed between 8 and 15, with the mean age being 13. The age of
onset of most anxiety disorders tends to be in childhood. SAD is more
common in children than in adolescents, whereas others such as
generalized anxiety disorder, panic disorder, and social anxiety
disorder tend to have a later onset and increase in frequency during
adolescence. Anxiety disorders in childhood can precede the
development of other comorbid psychiatric disorders like disruptive
behaviors and depression.
3. Answer E:
While there have been positive results for some medications in
randomized controlled studies for the treatment of social anxiety
disorder, there are no FDA-approved medications. The SSRIs are
considered to be first-line treatment of anxiety disorders in children
and adolescents. Positive results compared to placebo have been
found in studies of the SSRIs fluoxetine and paroxetine. Other
alternate medications that have been used include the SNRIs
venlafaxine, tricyclic antidepressants, benzodiazepines, the selective
norepineprhine reuptake inhibitor atomoxetine, and the serotonin 1A
agonist buspirone. The only anxiety spectrum disorder that has an
FDA-approved medication in children and adolescents is OCD.
4. Answer C:
The treatment of choice is CBT and social skills training. Exposure-
based CBT has the most evidence for anxiety disorders in children
and adolescents. There can be several components for CBT including
psychoeducation, cognitive restructuring, and problem solving and
exposure-relapse prevention. It may also involve interventions focused
at helping parents as well. However, those patients with more severe
anxiety symptoms might need a multimodal approach along with CBT.
The other psychotherapeutic approaches listed above do not have
much evidence to support their efficacy in children and adolescents.
Neurocognitive disorders (NCDs) (previously referred to in DSM-
IV as delirium, dementia, and amnestic disorders) begin with
delirium, followed by the syndromes of major NCD, mild NCD,
and their etiologic subtypes. Table 9-1 lists the Diagnostic and
Statistical Manual of Mental Disorders, 5th edition (DSM-5),
classification of neurocognitive disorders.
DELIRIUM
Delirium is a reversible state of global cerebral cortical dysfunction
characterized by alterations in attention and cognition and
produced by a definable precipitant. Frequently, disturbances in the
sleep–wake cycle are present. Delirium is categorized by its
etiology (Table 9-2) as caused by general medical conditions, as
substance-related, or as multifactorial in origin.
ETIOLOGY
Delirium is a syndrome with many causes, but it ultimately results
from global cerebral cortical dysfunction. The neurotransmitter
most commonly implicated in delirium is acetylcholine (Fig. 9-1).
Decreased central nervous system acetylcholine is thought to cause
delirium; however, increased dopamine and alterations in other
neurotransmitters such as γ-aminobutyric acid are also implicated.
Most frequently, delirium is the result of a general medical
condition; substance intoxication and withdrawal are also common
causes. Structural central nervous system lesions can also lead to
delirium.
TABLE 9-1. Neurocognitive Disorders

Delirium Major and Mild Neurocognitive Disorders
Medical condition Alzheimer’s disease
Substance intoxication Frontotemporal
Substance withdrawal Lewy bodies
Medication induced Vascular
Multiple etiologies Traumatic brain injury
Substance/medication induced
HIV
Prion disease
Parkinson’s disease
Huntington’s disease
Another medical condition
Multiple etiologies
TABLE 9-2. Common Causes of Delirium

General Medical Substance-Related
Infectious Intoxication
Urinary tract infections Alcohol
Meningitis Hallucinogens
Pneumonia Opioids
Sepsis Marijuana
Metabolic Stimulants
Hypernatremia Sedatives
Hepatic encephalopathy Withdrawal
Hypoxia Alcohol
Hypercarbia Benzodiazepines
Hyperglycemia Barbiturates
Fluid imbalance Medication induced
Uremia Anesthetics
Hypercalcemia Anticholinergics
Postsurgical Meperidine
Hyper/hypothyroidism Antibiotics
Ictal/postictal Toxins
Head trauma Carbon monoxide
Miscellaneous Organophosphates
Fat emboli syndrome
Thiamine deficiency
Anemia
FIGURE 9-1. The acetylcholinergic modulatory system. Projections to

cerebral cortex and the hippocampus arise from the medial septal
nuclei and the basal nucleus of Meynert. Projections to thalamus and
forebrain arise from the pontomesencephalotegmental complex.
(From Bear MF, Connors BW, Paradiso MA. Neuroscience: Exploring
the Brain, 4th ed. Philadelphia, PA: Wolters Kluwer, 2016.)
Table 9-2 lists common general medical and substance-related

causes of delirium. Delirium is often multifactorial and may be
produced by a combination of minor illnesses and minor metabolic
derangements (e.g., mild anemia, mild hyponatremia, mild
hypoxia, and urinary tract infection, especially in an elderly
person). Common medical causes of delirium include metabolic
abnormalities such as hyponatremia, hypoxia, hypercapnia,
hypoglycemia, and hypercalcemia. Infectious illnesses, especially
urinary tract infections, pneumonia, and meningitis, are often
implicated. The common substance-induced causes of delirium are
alcohol or benzodiazepine withdrawal and benzodiazepine and
anticholinergic drug toxicity, although a great number of
commonly used medications, both prescribed and available over
the counter, can produce delirium. Other conditions predisposing to
delirium include old age, fractures, and preexisting neurocognitive
disease. Brain damage of any kind, whether associated with overt
NCD, prior trauma, or ischemic changes, is a risk factor for the
development of delirium.
EPIDEMIOLOGY
The exact prevalence of delirium in the general population is
unknown. Delirium occurs in 10% to 30% of general medical
patients older than age 65 and is frequently seen postsurgically and
in intensive care units, where the prevalence of delirium in older
individuals can be over 80%. Delirium is equally common in men
and women.

The clinical history is critical in the diagnosis of delirium,
particularly in regard to the time course of development of the
delirium and to the prior existence of dementia or other psychiatric
illness. Key features of delirium are as follows:
1. Disturbance of consciousness, especially attention and level of

arousal
2. Alterations in cognition, especially memory, orientation,
language, and perception
3. Development over a period of hours to days
4. Presence of medical or substance-related precipitants
In addition, sleep–wake cycle disturbances and psychomotor

agitation may occur. Delirium is often difficult to distinguish from
a neurocognitive disorder, in part because NCDs are a risk factor
for delirium (and thus, they frequently co-occur), and also because
there is a great deal of symptom overlap, as outlined in Table 9-3.
Key differentiating factors are the time course of development of
the mental status change, especially if the patient did not have a
prior NCD, and the presence of a likely precipitant for the mental
status change. Individuals with delirium may also display periods
of complete lucidity interspersed with periods of confusion,
whereas in NCD, the deficits are generally more stable. In both
conditions, there may be nocturnal worsening of symptoms with
increased agitation and confusion (“sundowning”).
TABLE 9-3. Delirium Versus NCD

Delirium NCD
Onset Hours to days Weeks to years
Course/duration Fluctuates within a Stable within a day; may be
day; may last permanent, reversible, or
hours to weeksa progressive over weeks to years
Attention Impaired May be impaired
Cognition Impaired memory, Impaired memory, orientation,
orientation, language, executive function
language
Perception Hallucinations, Hallucinations, delusions
delusions,
misinterpretations
Sleep/wake Disturbed, may Disturbed, may have no pattern
have complete
day/night reversal
Mood/emotion Labile affect Labile affect; mood disturbances
Sundowning Frequent Frequent
Identified Likely precipitant Identifiable precipitant not
precipitant is present required
aThe DSM-5 does not specify a limit for the duration for delirium; clinical experience suggests
resolution within days to weeks, in most cases.
NCD, neurocognitive disorder.
The available evidence suggests that there are subtypes of

delirium identifiable via clinical observation of psychomotor
activity. These can be characterized as hypoactive, hyperactive, and
mixed deliria. Further research is needed to validate these subtypes
and develop subtype-specific treatment strategies. An assessment
for possible delirium in a quiet, or hypoactive patient, may be
critical in the overall medical treatment of such a patient.
The diagnosis of delirium is complicated by the fact that there
are no definitive tests for delirium; however, the confusion
assessment method for the intensive care unit evaluation is
becoming more commonly used as a delirium screening measure.
The workup for delirium includes a thorough history and
mental status examination, a physical examination, and laboratory
tests targeted at identifying general medical and substance-related
causes. These should include urinalysis, complete chemistry panel,
complete blood count, drug screen, and oxygen saturation.
Additional workup might entail chest radiographs, arterial blood
gas assessment, neuroimaging, or electroencephalogram. An
electroencephalogram may reveal nonspecific diffuse slowing. The
presence of a delirium is associated with a 1-year mortality rate of
40% to 50%.
Delirium should be differentiated from NCDs (although both can
be present at the same time), psychotic or manic disorganization,
and status complex partial epilepsy.
MANAGEMENT
The treatment of delirium involves keeping the patient safe from
harm while addressing the delirium. In the case of delirium
resulting from a general medical illness, the underlying illness must
be treated; in substance-related delirium, treatment involves
removing the offending drug (either drugs of abuse or medications)
or the appropriate replacement and tapering of a cross-reacting
drug to minimize withdrawal. Delirium in elderly individuals is
frequently multifactorial and requires correction of a multitude of
medical conditions. The essential element in the treatment of
delirium is to address all of the contributing medical issues.
In addition to addressing the cause of a delirium as the
mainstay of treatment, oral, intramuscular, or intravenous
haloperidol is of great use in treating delirium-associated agitation.
Atypical antipsychotic medications are also used; however, there
are no treatments for delirium approved by the U.S. Food and Drug
Administration. Although alcohol or benzodiazepine withdrawal
delirium is treated in part with benzodiazepines, benzodiazepines
may worsen or precipitate delirium arising from other causes.
Providing the patient with a brightly lit room with orienting cues
such as names, clocks, and calendars is also useful.
MAJOR AND MILD NEUROCOGNITIVE

DISORDERS
A major neurocognitive disorder is characterized by significant
cognitive decline in one or more of the following cognitive
domains: attention, executive function, learning and memory,
language, perceptual-motor, or social cognition. The cognitive
deficits must impair activities of daily living (ADLs) for a “major”
NCD diagnosis. Major NCD corresponds to dementia as identified
in DSM-IV. If the deficits do not impair ADLs, they are classified
as the “mild” subset of the illness. Determination of major versus
mild is subjective and based on a continuum of cognitive and
functional impairment. Specifiers allow for the differentiation of
disorders by severity and with or without behavioral disturbance.
Neurocognitive disorders are categorized according to etiology
(Table 9-1). They can arise as a result of a specific disease, for
example, Alzheimer’s disease (AD); a general medical condition; a
substance-related condition; or they can have multiple etiologies.
The definitive cause(s) may not be determined until autopsy.
ETIOLOGY
Generally, the etiology of NCD is brain neuronal loss that may be
caused by neuronal degeneration or cell death secondary to trauma,
infarction, hypoxia, infection, brain protein inclusions or
derangements, or hydrocephalus. Table 9-1 lists the major discrete
illnesses known to produce NCD. In addition, there are a large
number of general medical, substance-related, and multifactorial
causes of dementia.
EPIDEMIOLOGY
The prevalence of major neurocognitive disorder of all types is
about 1% to 2% at age 65, increasing with age to a prevalence of
about 30% by age 85. Specific epidemiologic factors relating to
disease-specific causes of dementia are listed in Table 9-4.

Neurocognitive disorders are diagnosed in the presence of
cognitive deficits not better explained by another diagnosis,
including delirium. The cognitive impairment required for
diagnosis in the DSM-5 can be in any one or more domains of
attention, executive function, learning and memory, language,
perceptual-motor, or social cognition. It is possible to be diagnosed
with an NCD without having memory impairment. Table 9-3
compares characteristics of NCD with those of delirium. NCDs
often develop insidiously over the course of weeks to years
(although it may be abrupt after head trauma or vascular insult).
Individuals with NCD usually have a stable presentation over brief
periods of time, although they may also have nocturnal worsening
of symptoms (“sundowning”). Memory impairment is often
greatest for short-term memory. Recall of names is frequently
impaired, as is recognition of familiar objects. Executive functions
of organization and planning may be lost. Paranoia, hallucinations,
and delusions are often present. Eventually, individuals with NCD
may become mute, incontinent, and bedridden.
NCDs should be differentiated from delirium. In addition, NCD
should be differentiated from those developmental disorders (such
as intellectual disability) with impaired cognition. Individuals with
major depression and psychosis can appear to suffer from an NCD;
they warrant a diagnosis of NCD only if their cognitive deficits
cannot be fully attributed to the primary psychiatric illness.
A critical component of differential diagnosis of NCDs is to
distinguish cognitive impairment associated with depression,
previously referred to as “pseudodementia.” Although there are
many precise criteria for separating the two disorders,
neuropsychologic testing may be beneficial to make an accurate
diagnosis. In cognitive changes related to depression, mood
symptoms are prominent, and individuals may report cognitive
changes, particularly in attention. They characteristically give “I
don’t know” answers to mental status examination queries, but may
answer correctly if pressed and encouraged. In addition, memory is
intact with rehearsal, which is not true for dementia.
MANAGEMENT
NCDs from reversible, or treatable, causes should be managed first
by treating the underlying cause of the disorder; rehabilitation may
be required for residual deficits. Reversible (or partially reversible)
causes of NCD include traumatic brain injury, normal pressure
hydrocephalus; neurosyphilis; human immunodeficiency virus
infection; and thiamine, folate, vitamin B12, and niacin deficiencies.
NCD from vascular insults may not be reversible, but their progress
can be halted in some cases.
Nonreversible NCDs are usually managed by placing the
patient in a safe environment and by medications targeted at
associated symptoms. There are four acetylcholinesterase inhibitor
medications (tacrine, rivastigmine, donepezil, and galantamine)
approved for the treatment of AD. The acetylcholinesterase
inhibitors improve cognitive function and global function. Tacrine,
the first approved for the treatment of AD, has a high rate of
hepatotoxicity and was discontinued in the United States owing to
safety concerns.
High-potency antipsychotics (in low doses) are used when
agitation, paranoia, and hallucinations are present. In addition,
atypical antipsychotic medications may be used for
neuropsychiatric symptoms, but appear to increase the risk of
stroke and other forms of mortality in elderly individuals. Although
low-dose benzodiazepines and trazodone are used for anxiety,
agitation, or insomnia, both may increase the risk of falls and
should be used sparingly.
FIGURE 9-2. Neuronal degeneration progresses over time, leading to
worsening severity of Alzheimer’s disease (AD). Blue-green colors
depict neuronal degeneration and volume loss. (A) Preclinical AD. (B)
Mild to moderate AD. (C) Severe AD. (Courtesy of the National
Institute on Aging/National Institutes of Health.)
SUBTYPES OF NEUROCOGNITIVE
DISORDERS
As previously mentioned, subtypes of major and mild
neurocognitive disorders are listed in Table 9-4. Previously, a
group of disorders with isolated disturbances of memory without
impairment of other cognitive functions were grouped as “amnestic
disorders”; however, this category has been eliminated in DSM-5.
Additional subtypes of NCDs are identified as major or mild NCD
due to another medical condition, multiple etiologies, or
unspecified NCD. If a substance is considered the underlying
cause, it is diagnosed as substance-induced NCD.
TABLE 9-4. Specific Subtypes of Major and Mild NCDs

Disease Description
AD Most common cause of dementia. Accounts for
50%–60% of all cases. The clinical course is
gradual and progressive as brain volume loss
ensues (Fig. 9-2). The typical presentation is
amnestic (i.e., impairment in memory and
learning). Social cognition tends to be preserved
until late in the course of the disease. Risk factors
are genetic, Down’s syndrome, TBI, and
increasing age. Postmortem pathology reveals
cortical atrophy, tau-predominant neurofibrillary
tangles, amyloid plaques, and loss of basal
forebrain cholinergic nuclei (Figs. 9-1 to 9-3).
Death occurs approximately 8–10 years after
diagnosis. Figure 9-2. Neuronal degeneration
progresses over time, leading to worsening
severity of Alzheimer’s disease (AD). Blue-green
colors depict neuronal degeneration and volume
loss. (A) Preclinical AD. (B) Mild to moderate
AD. (C) Severe AD. (Courtesy of the National
Institute on Aging/National Institutes of Health.)
Frontotemporal Common cause of NCD in ages less than 65 years
old. Approximately 5% of all cases of NCD.
Progressive development of behavioral and
personality change and/or language impairment.
Cognitive decline is less prominent. Frontal and
temporal atrophy are prominent on neuroimaging
and glucose metabolism is greatly reduced in
frontal regions in frontotemporal dementia, in
comparison with AD where temporal and parietal
regions show greater reductions (Fig. 9-4). The
dementia responds poorly to psychotropic
medicine. Associated with genetic mutations and
motor neuron disease. Death occurs
approximately 3–4 years after diagnosis.
Lewy body Progressive cognitive impairment with early
changes in complex attention and executive
function rather than learning and memory. Vivid
visual hallucinations, symptoms of rapid eye
movement sleep behavior, depression, autonomic
instability, spontaneous parkinsonism, and
delusions. The symptoms fluctuate in a pattern
that can resemble a delirium. Lewy bodies are
prominent (Fig. 9-5). Death in approximately 5–7
years after diagnosis.
Vascular Second most common cause of NCD. Risk factors
are cardiovascular and cerebrovascular disease.
Clinical evidence of cerebrovascular disease
includes documented history of stroke, with
cognitive decline temporally associated with the
event, or physical signs consistent with stroke.
Neuroimaging reveals multiple areas of neuronal
damage and may be focal, multifocal, or diffuse.
Course can be rapid onset or more slowly
progressive. Deficits are not reversible, but
progress can be halted with appropriate treatment
of vascular disease.
TBI Most common among those less than 4 years old,
older adolescents, and those older than 65 years.
TBI includes loss of consciousness, posttraumatic
amnesia, disorientation and confusion, or
neurologic signs. The cognitive presentation is
variable and may be accompanied by disturbances
in emotional function, personality changes, and
physical symptoms. Falls are the most common
cause of TBI, followed by motor vehicle
accidents.
Substance/medication Cognitive deficits persist beyond the usual
induced duration of intoxication and acute withdrawal of
the said substance. Risk factors include older age,
longer use, and persistent use past age 50 years.
HIV Limited to cases caused by direct action of HIV
on the brain; associated illnesses, such as
meningitis, lymphoma, and toxoplasmosis-
producing dementia are categorized under
dementia caused by general medical conditions.
Progression follows a “subcortical” pattern,
involving deep white matter. Symptoms include
personality changes, altered social behavior,
cognitive deficits, and motor abnormalities such
as psychomotor slowing. An estimated 25% of
individuals with HIV meet criteria for mild NCD
and fewer than 5% for major NCD.
Prion disease A group of subacute spongiform encephalopathies
caused by prions, the most common type is
sporadic CJD. Symptoms vary by type but for
CJD, neurologic signs and major neurocognitive
impairment occur within the first few months,
with death occurring in the first year of illness.
Genetic in up to 15% of cases. Wide age of onset
—teenage to late-life. Definitively confirmed only
by biopsy or at autopsy.
PD To diagnose NCD due to PD, cognitive symptoms
must present after the diagnosis of PD. Patients
may present with slowed thinking and impaired
memory, and personality change including
fearfulness or irritability, depressed mood,
insomnia, and reduced motivation. As many as
75% of individuals with PD will develop a major
NCD. The distinction between NCD, Lewy body
dementia, and PD subtypes is based only on the
timing and sequence of motor and cognitive
symptoms.
Huntington’s disease Cognitive changes consist of decline in executive
function more so than learning and memory.
There can be a range of motor abnormalities with
bradykinesia and chorea prominent. Risk factors
are familial, autosomal dominant cytosine adenine
guanine (CAG) trinucleotide repeat on
chromosome 4. Onset commonly in mid-30s.
Median survival approximately 15 years after
motor symptom diagnosis. Emotional lability is
prominent. Marked atrophy of the caudate and
putamen is present on autopsy (Fig. 9-6).
AD, Alzheimer’s disease; CJD, Creutzfeldt-Jakob’s disease; HIV, human immunodeficiency virus;
NCDs, neurocognitive disorders;
PD, Parkinson’s disease; TBI, traumatic brain injury.
FIGURE 9-3. Alzheimer’s disease is characterized by senile plaques,
neurofibrillary tangles, and amyloid deposition. White arrow points to
neurofibrillary tangles. (From Espay A, Biller J. Concise Neurology.
Philadelphia, PA: Wolters Kluwer, 2011.)
FIGURE 9-4. Alzheimer’s disease is characterized by reduced glucose

metabolism in parietal regions (white arrows). In contrast,
frontotemporal dementia is characterized by reduced frontal
metabolism ( yellow arrows). (From Louis ED, Mayer SA, Rowland LP.
Merritt’s Neurology, 13th ed. Philadelphia, PA: Wolters Kluwer, 2016.
Image courtesy of Robert Innis and William Charles Kreisl, Molecular
Imaging Branch, National Institute of Mental Health.)
FIGURE 9-5. . (A) α-Synuclein aggregates in Lewy bodies in
amygdala (arrows). Arrowheads point to neural processes. (B)
Enlarged Lewy body in substantia nigra (arrow). (C) Lewy bodies in
neocortex (arrows). (From Sadock BJ, Sadock VA, Ruiz P. Kaplan
and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical
Psychiatry, 11th ed. Philadelphia, PA: Wolters Kluwer, 2015. Courtesy
of Dr. Ronald L. Hamilton, Department of Pathology, Division of
Neuropathology, University of Pittsburgh School of Medicine.)
ETIOLOGY
NCD disorders can be due to other medical conditions or multiple
etiologies. Common general medical conditions that can cause
NCDs include structural lesions, hypoxia, nutritional conditions,
and immune disorders, among other causes. These disorders often
are associated with damage of the mammillary bodies, fornix, and
hippocampus. Bilateral damage to these structures produces the
most severe deficits. Neurocognitive disorders resulting from
substance-related causes may be the result of substance abuse, use
of prescribed or over-the-counter medications, or accidental
exposure to toxins. Alcohol use disorder is a leading cause of
substance-related NCD. A diagnosis of unspecified NCD is given
when criteria for major or mild NCD are met, but the precise
etiology cannot be determined.
FIGURE 9-6 (A) Section of neocortex from a patient with Huntington’s

disease that is stained with antibody to huntingtin protein to
demonstrate neuronal intranuclear inclusions. (B) Brain section from
patient who died of Huntington’s disease on left and control brain on
right, demonstrating marked atrophy of caudate and putamen. (From
Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock’s Comprehensive
Textbook of Psychiatry, 10th ed. Philadelphia, PA: Wolters Kluwer,
2017. Photographs courtesy of Dr. Christopher A. Ross.)
EPIDEMIOLOGY
Individuals affected by a general medical condition or substance
use disorder are at risk for neurocognitive disorders.

When the NCD is due to another medical condition, the cognitive
progression goes along with the course of illness. For example, if
the cause is treatable (e.g., vitamin deficiency), deficits may
stabilize or even improve with treatment. If the illness is
progressive (e.g., multiple sclerosis), cognitive deficits would also
progress.
Delirium and specific subtypes of NCDs are the major differential
diagnostic considerations. By definition, these NCDs are
distinguished on the basis of etiology, determined by time course,
patient history, cognitive domain involvement, and associated
symptoms.
MANAGEMENT
The general medical condition is treated whenever possible to
prevent further neurologic damage. In the case of a substance-
related NCD disorder, avoiding reexposure to the substance
responsible for the disorder is critical. Pharmacotherapy may be
directed at treating associated neuropsychiatric symptoms, such as
depressed mood or anxiety. As mentioned with other NCDs,
patients should be placed in a safe, structured environment with
frequent memory cues.
KEY POINTS
Delirium is a disorder of attention and cognition
likely resulting from alterations in multiple
neurotransmitters.
There are hypoactive, hyperactive, and mixed
subtypes of delirium.
Delirium has an identifiable precipitant, an abrupt
onset, and a variable course.
The 1-year mortality rate for delirium is greater
than 40%.
NCD is a disorder of attention, executive function,
learning and memory, language, perceptual-motor,
or social cognition.
NCDs may be caused by a variety of illnesses or
substances and have a gradual onset and
progressive course.
NCD predisposes to delirium.
CLINICAL VIGNETTES
VIGNETTE 1
A 69-year-old widowed female patient is admitted to the cardiac
surgery service after developing an infection of her sternotomy site
following a coronary artery bypass graft. Two days after admission,
the nursing staff expresses concern because she appears to be
intermittently confused, particularly at night. The primary team urgently
consults you in your capacity as the on-call hospital psychiatrist when
the patient is observed to be acutely agitated and trying to call the
police because she believes that there are burglars in her room. On
assessment, you find an anxious elderly woman who is inattentive to
your questions, disoriented as to time and place, and cannot recall a
list of three items at 5 minutes.
1. Which of the following is the most likely diagnosis?

a. Delirium
b. Dementia
c. Dissociative amnesia
d. Major depressive disorder
e. Schizophrenia
2. In addition to therapy targeting her underlying medical conditions,

which of the following would be the most appropriate initial
treatment intervention for this patient?
a. Lorazepam
b. Diphenhydramine
c. Fluoxetine
d. Haloperidol
VIGNETTE 2
A 73-year-old woman is brought to your office because she has vivid
hallucinations of children and small animals when she is alone in a
room. Her family also notes that her movements and gait have
slowed, and she has noticeable mild hand tremors when she is at rest.
Her husband complains that he has to sleep in a separate room
because she hits him in her sleep. She has a 7-month history of short-
term memory loss, fluctuating disorientation, difficulty managing her
finances, preparing meals, and following storylines while watching TV.
Her score on the Mini–Mental State Examination is 23 of 30. On
physical examination, she has cogwheel rigidity and a resting tremor
in her upper extremities.
1. Which of the following is the most likely subtype of major

neurocognitive impairment?
a. Alzheimer’s disease (AD) (major neurocognitive disorder due to
AD)
b. Dementia with Lewy bodies (DLBs) (major neurocognitive
disorder with Lewy bodies)
c. Frontotemporal dementia (FTD) (major frontotemporal
neurocognitive disorder)
d. Huntington’s disease (major neurocognitive disorder due to
Huntington’s disease)
VIGNETTE 3
A 59-year-old man is brought to your office by his family because of
concerns about dramatic changes to his personality over the past
year. He is more irritable and made several inappropriate comments in
social settings to friends and family. A coworker filed a complaint for
sexual harassment and he was placed on leave from his job. Despite
this, he has little insight into how his behaviors have offended others
and seemingly has no remorse. In addition, he has gained 20 lb in the
past 4 months because he is eating a pint of ice cream and drinking
Dr. Pepper every night after dinner. There is a family history of early-
onset dementia.

a. AD (major neurocognitive disorder due to AD)
b. Human immunodeficiency virus (HIV)-related dementia (major
neurocognitive disorder due to HIV infection)
c. Huntington’s disease (major neurocognitive disorder due to
Huntington’s disease)
d. FTD (major frontotemporal neurocognitive disorder)
e. Vascular dementia (major vascular neurocognitive disorder)
2. What would you expect to find on neuroimaging?

a. Generalized atrophy, but more prominent in tempo-parietal
lobes
b. Frontal and temporal atrophy, slightly asymmetric
c. Hippocampal atrophy
d. Moderate to severe white matter hyperintensities
3. What other illness is associated with this disease?

a. Amyotrophic lateral sclerosis (ALS)
b. Parkinson’s disease
c. Binswanger’s disease
d. Trisomy 21
4. Which subtype of FTD does this patient most likely have?

a. Primary progressive aphasia (fluent/semantic)
b. Behavioral variant
c. Primary progressive aphasia (agrammatic/nonfluent variant)
d. Primary progressive aphasia (logopenic variant)
VIGNETTE 4
A 67-year-old man comes to your outpatient office to establish care.
His history includes mild hypertension. The patient is married and
maintains an active professional and social life. He is physically active,
does not smoke, and drinks one to two glasses of wine daily.
Medications include hydrochlorothiazide 12.5 mg per day, aspirin 81
mg per day, and a daily multivitamin. His family history is notable for
an 84-year-old maternal aunt who recently died after 6 years in the
memory-disorders unit of a nursing home. His aunt’s death has
caused the patient to worry about his own risk of dementia. He
requests a referral for genetic testing for AD. Physical examination is
unremarkable.
4. Which of the following is true about risk of AD (major

neurocognitive disorder due to AD)?
a. There is no evidence for autosomal dominant inheritance in AD
b. The prevalence of AD is about 10% in people over 65
c. The apolipoprotein epsilon 2 (E2) allele increases the risk for
AD
d. African Americans have a lower risk for AD than do whites
2. In AD, typical microscopic pathologic findings consist of:

a. Lewy bodies
b. Senile plaques, neurofibrillary tangles, and amyloid deposition
c. Loss of dopamine neurons in the substantia nigra (SN) and
ventral tegmental area (VTA)
d. Loss of medium spiny γ-aminobutyric acid (GABA) neurons of
the caudate nucleus and putamen
ANSWERS
1. Answer A:
This patient is exhibiting signs of delirium, with acute global cognitive
dysfunction, likely precipitated by infection. Clues include acute onset
over the course of days, impairment in attention, waxing and waning
of conscious level over the course of the day with particular confusion
and agitation at night (“sundowning”), and impaired memory and
orientation. Dementia typically has a more insidious course and
features prominent memory impairment in the absence of altered
conscious level. Dissociative amnesia involves the temporary inability
to recollect important personal information. Major depressive disorder
can present with apparent memory impairment termed
pseudodementia, but patients typically exhibit normal cognitive
functioning with encouragement and careful interviewing. Although
intermittent psychotic symptoms (particularly hallucinations) may
occur in delirium, schizophrenia requires the persistence of psychotic
symptoms and social or occupational dysfunction for at least 6
months.
2. Answer D:
The primary treatment for delirium is to identify and treat the
underlying medical causes that are precipitating or maintaining the
delirium. Specific pharmacologic treatment for delirium can be
beneficial in controlling symptoms and behavior, although treatment
does not appear to alter the course of the delirium. The most
commonly used medications for treating delirium are high-potency
typical antipsychotics or, more recently, atypical antipsychotics.
Haloperidol is primarily an antagonist at the dopamine 2 receptor and
has shown efficacy in treating the symptoms of delirium. Lorazepam is
a benzodiazepine medication with GABA agonist properties.
Benzodiazepines are used in the treatment of alcohol withdrawal
delirium but are not indicated for delirium due to other causes.
Diphenhydramine is an antihistamine that has anticholinergic
properties. Anticholinergic medications worsen delirium and hence
should be avoided when possible in patients with delirium. Fluoxetine
is an SSRI medication primarily used as an antidepressant.
1. Answer B:
Core features of DLBs (major neurocognitive disorder with Lewy
bodies) include fluctuations in attention/alertness, recurrent and vivid
visual hallucinations, and parkinsonian features that develop 1 year
after cognitive impairment. Suggestive features of DLB include rapid
eye movement sleep behavior disorder and sensitivity to neuroleptics.
AD (major neurocognitive disorder due to AD) is gradual and
progressive and typically presents as amnestic (i.e., impairment in
memory and learning). Social cognition tends to be preserved until
late in the course of the disease. Risk factors for AD are genetic,
Down’s syndrome, traumatic brain injury, and increasing age. FTD
(major frontotemporal neurocognitive disorder) presents with
progressive development of behavioral and personality change and/or
language impairment depending on the variant. Cognitive decline is
less prominent. Huntington’s disease (major neurocognitive disorder
due to Huntington’s disease) presents with cognitive changes consist
of decline in executive function more so than learning and memory.
There can be a range of motor abnormalities with bradykinesia and
chorea prominent.
1. Answer D:
This patient has developed the insidious onset of cognitive decline,
encompassing the prominent feature of marked personality change.
He is disinhibited, resulting in an inability to observe typical social
mores. The early age of onset of a major neurocognitive disorder and
family history of early-onset dementia are consistent with FTD. AD
(major neurocognitive disorder due to AD) typically presents after age
65 with insidious onset of short-term memory impairment. HIV-related
dementia (major neurocognitive disorder due to HIV infection)
presents as global cognitive decline usually in the late stages of AIDS.
Dementia due to Huntington’s disease (major neurocognitive disorder
due to Huntington’s disease) presents with other typical features of
Huntington’s disease including early onset (typically during the mid-
30s) and choreiform movements with prominent caudate atrophy on
neuroimaging. Vascular dementia typically presents with stepwise
cognitive decline in the setting of cardiovascular and cerebrovascular
risk factors. There may be focal findings on neurologic examination,
and neuroimaging typically shows multiple areas of pathology.
2. Answer B:
In FTD, frontal and temporal atrophy are prominent on neuroimaging
and glucose metabolism is greatly reduced in frontal regions in FTD,
in comparison with AD where temporal and parietal regions show
greater reductions. Generalized atrophy that is more prominent in
tempo-parietal lobes, along with hippocampal atrophy would be
consistent with expected neuroimaging finds in AD. Moderate to
severe white matter hyperintensities are more consistent with vascular
dementia. In vascular dementia, there is clinical evidence of
cerebrovascular disease that includes documented history of stroke,
with cognitive decline temporally associated with the event, or physical
signs consistent with stroke. Neuroimaging reveals multiple areas of
neuronal damage and may be focal, multifocal, or diffuse.
3. Answer A:
FTD is associated with motor neuron disease and can co-occur with
ALS. This shared risk appears to be conferred by abnormalities in the
trans-activation response element (TAR) DNA-binding protein 43,
which is linked to multiple neurodegenerative diseases. Binswanger’s
disease is associated with vascular dementia and is a somewhat
imprecise term but generally refers to dementia associated with
subcortical periventricular leukoencephalopathy. Trisomy 21 is linked
with Alzheimer’s dementia. Parkinson’s disease would be related to
Parkinson’s disease dementia; however, if cognitive symptoms were
present for 1 year before the development of parkinsonian symptoms,
the diagnosis would be consistent with DLBs.
4. Answer B:
This patient displays symptoms consistent with behavioral variant
FTD. In addition to behavioral variant FTD, there are three language-
related variants of this condition. Behavioral variant is the most
common and accounts for over half of the cases of FTD. In the
fluent/semantic variant, patients have word-finding difficulty common
across all variants but also have difficulty with word comprehension
and naming but are otherwise fluent with preserved grammar. In the
agrammatic/nonfluent primary progressive aphasia variant patients
have word-finding difficulty common across all variants but also have
difficulty with articulation. In the logopenic variant, patients have word-
finding difficulty common across all variants but also have difficulty
with word retrieval in the face of preserved naming.
1. Answer B:
The prevalence of AD is about 10% of people over 65. AD (major
neurocognitive disorder due to AD) is genetically influenced. Less than
1% of cases are autosomally dominant and are associated with early
onset (roughly before age 65) AD. A polymorphism in the
apolipoprotein gene is associated with risk for AD, with the E4 allele
conveying the greatest risk, the E3 having a neutral effect, and the E2
allele demonstrating a protective effect. Increasing age is the biggest
risk factor for the development of AD with about 10% of people above
age 65 having AD. Race and ethnicity do influence AD risk and
African Americans have an increased risk (approximately double) that
of whites.
2. Answer B:
Neurofibrillary tangles are composed largely of hyperphosphorylated
tau protein and are found in a range of conditions, known as
tauopathies. Amyloid deposition with degenerating neurons contribute
to the formation of senile plaques. Lewy bodies are most
characteristically associated with Lewy body dementia (major
neurocognitive disorder due to Lewy body dementia) and consist of α-
synuclein aggregates. Loss of dopamine neurons in the SN and VTA
is most commonly associated with Parkinson’s disease but is also
seen in association with Lewy body dementia which has parkinsonian
features.
Substance abuse is as common as it is costly to society. It is
etiologic for many medical illnesses and is frequently comorbid
with psychiatric illness. The Diagnostic and Statistical Manual of
Mental Disorders, Fifth edition (DSM-5) made several significant
changes in the way substance use disorders are defined. The
distinction between substance use and dependence that was once
defined in DSM-IV has been eliminated. Legal problems no longer
factor into the diagnosis of substance use disorder. Gambling
disorder (not further discussed here) has been added to the chapter
to reflect the similarities of a behavioral pattern that is not related
to pharmacologic effects of a substance on the brain. Other
disordered behaviors with evidence of loss of control that have the
potential to be considered addictive were not included (overeating,
sex, Internet use) in this updated version of the diagnostic manual,
but cause individuals considerable distress and suffering and are
often the focus of concern. Substance use disorders are defined
independently of the substance. Hence, alcohol use disorder is
defined by the same criteria as opioid use disorder. DSM-5 does
distinguish specific intoxication and withdrawal syndromes that are
characteristic of the 10 classes of drugs included in the manual
(Table 10-1). This chapter defines substance use disorder, provides
clinical descriptions of each substance-related disorder, and
describes the intoxication and withdrawal syndromes related to the
most common drugs of abuse.
TABLE 10-1. DSM-5 Drug Classes

Alcohol Inhalants
Caffeine Opioids
Cannabis Sedatives, hypnotics, or anxiolytics
Hallucinogens–phencyclidines Stimulants
Hallucinogens–other Tobacco
SUBSTANCE USE DISORDER

Table 10-2 outlines the general criteria for diagnosing a substance
use disorder. Symptoms and behaviors associated with substance
use occur in four main domains. In the domain of impaired
control, symptoms include using more of a substance or using it
longer than initially planned, attempts to cut down or reduce
substance use that do not succeed, devoting time and effort to
thinking about or trying to obtain the substance, and conscious
recognition of a desire for the substance (craving). Substance use
has a major impact on one’s relationships with others. In the
domain of social impairment, symptoms include use of substances
that interferes with one’s role at work, home, or school; continuing
to use the substance despite negative consequences of substance
use; and giving up other activities such as socializing with friends,
hobbies, and so on, in favor of substance use. In the domain of
risky use, symptoms/behaviors include using a substance when it
is physically dangerous (e.g., while driving) and continuing to use
substances despite evidence that the substance use is causing a
psychological problem or a physical problem (e.g., alcohol-induced
hepatitis). The pharmacologic domain indirectly reflects the
effects of the substance on the brain and body, with tolerance to the
substance defined as requiring a greater amount of the substance to
get the same effects as when one initially started using it and
symptoms of substance withdrawal when the substance is
discontinued after a period of prolonged use.
Substance use disorders are defined as mild if two to three
criteria from Table 10-2 are met, moderate if four to five criteria
are met, and severe if six or more criteria are met. Although each
substance use disorder has unique features, including a specific
intoxication and/or withdrawal syndrome, that are characteristic of
the substance used, these are the common features that define
substance use disorder.
TABLE 10-2. Criteria for Substance Use Disorder

Domain Symptom/Behavior
Impaired Using more than planned
control Loss of control/inability to cut down
A great deal of time is spent with the drug
Craving
Social Interference with role
impairment Continued use despite consequences
Giving up other activities
Risky use Using drug when physically dangerous
Continued use in the presence of a physical or
psychological problem
Pharmacologic Tolerance
Withdrawal
Criteria for substance use disorder include two or more of the given symptoms resulting from
substance use that cause impairment or distress within a 12-month period.
It is important to note that physiologic dependence on a

substance may occur in the absence of substance use disorder.
Tolerance to the pain-relieving effects of an opioid may result in a
requirement to increase doses of prescribed medications to obtain
pain control, and withdrawal may occur if the opioid drug is
abruptly stopped. In this circumstance, opioid use disorder would
only be diagnosed if use of the drug is causing a clinically
significant problem. Risk for substance use disorder or addiction is
of particular concern in management of acute and chronic pain.
NEURAL BASIS
As with all psychiatric disorders, substance use disorders are
structural and functional brain disorders rooted firmly in
neurobiology. Substance use disorders develop through a
biopsychosocial interaction whereby genetic effects and
environment interact to culminate in a behavioral pattern of
repeated drug use. Substance use disorders develop when a person
is repeatedly exposed to a substance. Although the degree to which
genetic factors explain the risk for abuse of or dependence on a
particular substance vary, a disorder develops when a person is
biologically vulnerable, has access to the substance, and is
repeatedly exposed to the substance with ongoing availability. In
addition to biologic vulnerabilities that preexist the use of a
particular substance, exposure of the brain to the drug has
secondary consequences, whereby the direct chemical effects of the
drug change brain structure and function with repeated exposure.
With repeated exposure, gene expression changes and neuronal
plasticity alter the brain so that substance use increasingly recruits
neural circuits involved in habit learning. Once addiction is
established, specific phases of the addiction map onto specific
neural circuitry.
The specific brain effects vary with the chemical composition
of a given drug; however, current evidence suggests that addictive
substances act by a final common pathway influencing neurons of
the ventral striatum/nucleus accumbens. Addictive behaviors such
as overeating, gambling, sex, and possibly Internet use also engage
this final common pathway. The ventral striatum/nucleus
accumbens is a target of the mesocorticolimbic dopamine pathway
that mediates reward system function (Figs. 10-1 and 15-1).
Naturally occurring rewards having high evolutionary adaptive
significance (such as feeding, sex, and exercise) interact with the
mesolimbic dopamine pathway to produce associative memories
linked to the rewards that reinforce the probability of rewarding
behavior. Drugs of abuse bypass the adaptive components of the
reward system and, via direct synaptic effects, produce similar
powerful associative memories strongly reinforcing behavior
associated with drug use (Fig. 10-1). The γ-aminobutyric acid
(GABA)-containing medium spiny neuron of the ventral
striatum/nucleus accumbens is the final common target of all drugs
of abuse and all natural rewards. These neurons are either indirectly
activated by drug effects on the dopamine neurons of the ventral
tegmental area that project into the nucleus accumbens; directly
affected by drugs such as alcohol, phencyclidine, cannabis,
cocaine, amphetamine, and opioids; or both.
FIGURE 10-1. Upper left: Mid-sagittal brain depicting dopaminergic
VTA to NAc projection (red) and glutamatergic prefrontal cortex to
NAc projection (black). Upper right panel depicts site of action for
opioids, cannabinoids, and nicotine to increase DA release from VTA
dopaminergic neuron. Lower left panel depicts dopaminergic input
from VTA (axon labeled DA) to an NAc medium spiny GABA neuron.
The NAc medium spiny GABA neuron is the final common pathway for
all known natural rewards and drugs of abuse. Drugs act indirectly
through increasing DA release or directly on NAc medium spiny GABA
neurons. Ach, acetylcholine; CB1, cannabinoid 1 receptor; DA,
dopamine; DAT, dopamine reuptake transporter; GABA, γ-
aminobutyric acid; NAc, nucleus accumbens; NMDA-R, glutamatergic
N-methyl-d-aspartate receptor; PCP, phencyclidine. (From Golan DE.
Principles of Pharmacology, 4th ed. Philadelphia, PA: Wolters Kluwer,
2017.)
Because addiction occurs when repeated exposure to drugs has

produced alterations in the brain’s reward system and in other brain
regions involved in salience attribution, executive function
(inhibitory control, decision making, planning), introspection,
stress reactivity and mood, and habits and drive, there are
conscious and nonconscious elements predisposing to continued
drug use despite adverse consequences of the drug (Fig. 10-2).
Treatment for addiction, therefore, must include an awareness of
the nonconscious factors (such as stress, exposure to drug cues,
hunger, etc.) that predispose to relapse.
FIGURE 10-2. Neuronal circuitry of addiction. Proposed neuronal

network of interacting brain regions and associated circuits that are
disrupted in addicted individuals. Changes occur in reward (NAc and
VTA), conditioning/memory (amygdala and medial OFC for emotional
and salience attribution; hippocampus and dorsal striatum for
memories and habits), executive control (ACC, inferior PFC, dlPFC,
and lateral OFC), motivation/drive (medial OFC for attribution of
salience, ventral ACC, VTA, dorsal striatum, NAc), interoception
(insula and ACC), and aversion/avoidance (habenula). This model
proposes that, during addiction, the enhanced expectation value of the
drug in the reward, motivation, and memory circuits overrides the
control circuits, favoring a positive-feedback loop initiated by
consumption of the drug and perpetuated by the enhanced activation
of the motivation/drive and memory circuits. These circuits also
interact with those involved in mood regulation, including stress
reactivity (which includes participation of the extended amygdala,
hypothalamus, and habenula) and interoception (which includes
participation of the insula, ACC, and the default mode network and
contributes to a heightened awareness of craving). ACC, anterior
cingulate cortex; dlPFC, dorsolateral PFC; NAc, nucleus accumbens;
OFC, orbitofrontal cortex; PFC, prefrontal cortex; VTA, ventral
tegmental area. (Reprinted from Volkow ND, Morales M. The brain on
drugs: from reward to addiction. Cell. 2015;162(4):712–725. With
permission from Elsevier.)
In addition to substance use disorders, persistent use of

substances can be related to symptoms that resemble other
psychiatric disorders. These include psychotic, bipolar, depressive,
anxiety, sleep, and neurocognitive disorders (delirium and
dementia) as well as sexual dysfunction. Careful attention to the
timeline of symptom development and course of substance use is
necessary to distinguish these conditions from the primary
disorders they resemble. Primary mood, anxiety, and psychotic
disorders as well as personality disorders are very commonly
comorbid with substance use disorders.
REHABILITATION AND RECOVERY

The two goals of rehabilitation are achieving abstinence and
treatment of comorbid psychopathology. To sustain a lasting
recovery, patients must acknowledge the illness and accept the
need for treatment. Twelve-step groups are commonly
recommended for patients with substance use disorders and can
provide an important source of support for individuals wishing to
maintain abstinence from substances and build new patterns of
behavior. The 12-step model originated in the 1930s as Alcoholics
Anonymous (AA), and has grown to encompass many problematic
behaviors including Narcotics Anonymous, Overeaters
Anonymous, Gamblers Anonymous, Sex Anonymous, and Debtors
Anonymous. The programs offer free support group meetings that
are available worldwide. Members are encouraged to work with a
sponsor, a peer with experience in the program, who volunteers to
be available at all times to support the member’s recovery. Some
patients find the program off-putting because of a spiritual
component that insists on the need to acknowledge a “higher
power.”
A significant factor influencing the cost to society of substance
use disorders is the profound impact these illnesses have on those
who care about the affected individual. Alanon is a 12-step
program that offers support for loved ones affected by substance
use disorder.
ALCOHOL-RELATED DISORDERS
ALCOHOL USE DISORDER

Alcohol use becomes problematic when an individual experiences
loss of control over use. Tolerance and withdrawal symptoms
develop and the individual is preoccupied by craving or thoughts
about when they might drink again. The patient with alcohol use
disorder drinks larger amounts of alcohol over longer periods of
time than intended in spite of a desire to cut down, spends a great
deal of time attempting to obtain alcohol, and reduces participation
in or eliminates important social, occupational, or recreational
activities because of alcohol. In alcohol use disorder, there is also
loss of control over alcohol intake. The popular mnemonic CAGE
is a useful screen for alcohol use disorder and captures several of
the problematic elements of the condition (Table 10-3).
TABLE 10-3. CAGE Questions

The CAGE questions are a popular screening tool for alcohol use disorder.
C “Have you tried to cut down or stop using and found that you were
not able to control your use?”
A “Do you find that you are annoyed when others express concern
about your use of alcohol?”
G “Do you often feel guilty about the consequences of your alcohol
use?”
E “Do you ever start the day with an ‘eye opener,’ using alcohol first
thing to prevent withdrawal?”
Epidemiology
A large percentage of Americans use alcohol; however, that vast
majority do not develop alcohol use disorders. The National
Institute on Alcohol Abuse and Alcoholism guidelines define high-
risk use as more than 4 drinks for men and 3 drinks for women on a
single occasion and more than 14 drinks for men and 7 drinks for
women in a week. The risk for developing alcohol use disorder is
far greater in individuals who exceed these recommended daily and
weekly limits. Two-thirds of Americans drink occasionally; 12%
are heavy drinkers, drinking almost every day and becoming
intoxicated several times a month. The Epidemiological Catchment
Area study found a lifetime prevalence of alcohol dependence of
14%. The male to female prevalence ratio for alcohol dependence
is 4:1.
Etiology
The etiology of alcohol dependence is unknown. Adoption studies
and monozygotic twin studies demonstrate a partial genetic basis,
particularly for men with alcoholism. Men with alcohol use
disorder are more likely than women with alcohol use disorder to
have a family history of alcoholism. Compared with control
subjects, the relatives of those with alcohol use disorder are more
likely to have higher rates of depression and antisocial personality
disorder. Adoption studies also reveal that alcoholism is
multidetermined: genetics and environment (family rearing) both
play a role.
History
The patient with alcohol use disorder may deny or minimize the
extent of drinking, making the early diagnosis of alcoholism
difficult. The patient may present with accidents or falls, blackouts,
motor vehicle accidents, or after an arrest for driving under the
influence. Because denial is so prominent in the disorder, collateral
information from close friends and family members is essential to
the diagnosis. Early physical findings that suggest alcohol
dependence include acne rosacea, palmar erythema, and painless
hepatomegaly (from fatty infiltration).
Physical Examination
Signs of more advanced alcohol use disorder include cirrhosis,
jaundice, ascites, testicular atrophy, gynecomastia, and
Dupuytren’s contracture. Cirrhosis can lead to complications
including variceal bleeding, hepatocellular carcinoma, and hepatic
encephalopathy. Medical disorders with an increased incidence in
patients with severe alcohol use disorder include pneumonia,
tuberculosis, cardiomyopathy, hypertension, and gastrointestinal
cancers (i.e., oral, esophageal, rectal, colon, pancreas, and liver).
Mental Status Examination
Alcohol influences on the mental status examination may range
from intoxication with agitation to unresponsiveness in overdose to
manifestations of brain damage. There are numerous
neuropsychiatric complications of alcohol dependence. Other
neuropsychiatric complications of alcoholism include alcoholic
hallucinosis, alcohol-induced dementia, peripheral neuropathy, and
mental status changes due to subdural hematoma or other
intracranial bleeding, substance-induced depression, and suicide. In
the later stages of alcoholism, significant social and occupational
impairment is likely: job loss and family estrangement are typical.
Laboratory Tests
Various laboratory tests are helpful in making the diagnosis. Blood
alcohol levels quantitatively confirm alcohol in the serum. They
can also provide a rough measure of tolerance. In general, the
higher the blood alcohol level without significant signs of
intoxication, the more tolerant the patient has become to the
intoxicating effects of alcohol.
Patients with alcohol use disorder also develop elevated mean
corpuscular volume, elevated serum glutamic-oxaloacetic
transaminase, and elevated serum glutamic-pyruvic transaminase.
Patients with alcohol use disorder are also more likely to have
evidence of old rib fractures on chest radiographs (30% in patients
with alcohol use disorder compared with 1% in control subjects).
The diagnosis of alcohol use disorder is usually clear after careful
history, physical and mental status examination, and consultation
with family or friends. The differential includes nonpathologic use
of alcohol, sedative/hypnotic use disorder, and conduct disorder or
antisocial personality disorder.
Management
Management is specific to the clinical syndrome. Alcohol
intoxication is treated with supportive measures, including
decreasing external stimuli and withdrawing the source of alcohol.
Intensive care may be required in cases of excessive alcohol intake
complicated by respiratory compromise. All suspected or known
alcohol-dependent patients should receive oral vitamin
supplementation with folate 1 mg per day and thiamine 100 mg per
day. If oral intake is not possible, or if there is concern that the
patient may have thiamine deficiency, recent malnutrition,
malabsorption, or early signs of Wernicke’s encephalopathy, then
thiamine should be administered intravenously as a slow infusion
before any glucose is given (because glucose depletes thiamine
stores).
Symptoms of acute thiamine deficiency may remit with the
slow intravenous infusion of thiamine at 500 mg three times per
day for 4 to 5 days. Magnesium repletion is also essential. Without
thiamine at sufficiently high dosages and given intravenously,
Wernicke’s encephalopathy may progress to a chronic condition of
alcohol-induced persisting amnestic disorder as described later.
ALCOHOL INTOXICATION
Alcohol intoxication is defined by the presence of slurred speech,
incoordination, unsteady gait, nystagmus, impairment in attention
or memory, stupor or coma, and clinically significant maladaptive
behavioral or psychological changes (inappropriate sexual or
aggressive behavior, mood lability, impaired judgment, impaired
social or occupational functioning) that develop during or shortly
after alcohol ingestion.
The diagnosis of alcohol intoxication must be differentiated
from other medical or neurologic states that may mimic
intoxication, for example, diabetic hypoglycemia; toxicity with
various agents, including but not limited to ethylene glycol,
lithium, and phenytoin; and intoxication with benzodiazepines or
barbiturates. The diagnosis of alcohol intoxication can be
confirmed by serum toxicologic screening, including a blood
alcohol level.
ALCOHOL WITHDRAWAL
Alcohol withdrawal is a potentially fatal complication of alcohol
use disorder. The complexity and time course of alcohol
withdrawal cannot be fully captured in a descriptive narrative, and
caregivers should be wary of assumptions regarding alcohol
withdrawal. Alcohol withdrawal commonly occurs with a
predictable course, but may show much individual variation. Table
10-4 summarizes the common time course of alcohol withdrawal
symptoms. Withdrawal is diagnosed after cessation or reduction in
alcohol intake is accompanied by two or more of the following
clinical signs: autonomic hyperactivity (sweating or heart rate
greater than 100 beats per minute), hand tremor, insomnia, nausea
or vomiting, perceptual distortions or hallucinations, psychomotor
agitation, anxiety, generalized tonic clonic seizures. Along with
delirium and Wernicke’s encephalopathy, seizures are among the
most serious complications of alcohol withdrawal.
TABLE 10-4. Alcohol Withdrawal
Sign or Symptom Onseta (hours)
Tremulousness (the shakes) 4–12
Perceptual disturbances 8–12
Seizures 12–24
Delirium 72
a Onset refers to the onset following the cessation of alcohol intake after a prolonged period of heavy
regular drinking. This is more accurately tied to the point at which alcohol blood levels decline.
While alternative treatment options are emerging, the primary

treatment for alcohol withdrawal is administration of
benzodiazepines.
ALCOHOL-RELATED NEUROCOGNITIVE DISORDERS

Alcohol withdrawal can be associated with delirium, often called
delirium tremens. Delirium tremens is a life-threatening condition
manifested by perceptual disturbances, confusion or disorientation,
agitation, autonomic hyperarousal, and elevated temperature. It
affects up to 5% of hospitalized patients with alcohol use disorder
and typically begins 2 to 3 days after abrupt reduction in or
cessation of alcohol intake. It is treated with intravenous
benzodiazepines and supportive care. Patients may require
treatment in an intensive care unit, particularly if there is
significant autonomic instability (e.g., rapidly fluctuating blood
pressure). The syndrome typically lasts 3 days, but can persist for
weeks.
The criteria for alcohol-induced persisting neurocognitive
disorder are similar to other types of neurocognitive disorders
(discussed in Chapter 9) in terms of the cognitive deficits,
consisting of deficits in memory, aphasia, apraxia, or agnosia, and
impaired executive function. The diagnosis is made when alcohol
is determined to be the cause of the cognitive changes.
Alcohol-induced persisting amnestic disorder is also classified
as an amnestic disorder under the heading of substance-induced
persisting amnestic disorder. Alcohol-induced persisting amnestic
disorder is also called Korsakoff’s syndrome and is irreversible in
two-thirds of patients. Alcohol-induced persisting amnestic
disorder is diagnosed in an individual with a history of alcohol
dependence who develops memory impairment in learning new
memories or recalling old information. Confabulation (i.e., making
up information to fill gaps in memory) is common.
Wernicke-Korsakoff’s syndrome (classified as a
neurocognitive disorder in DSM-5) may develop in the patient with
alcohol use disorder because of thiamine deficiency. The acute
Wernicke’s stage of the syndrome is also called Wernicke’s
encephalopathy. Wernicke’s encephalopathy consists of the triad of
eye movement abnormalities, ataxia, and mental confusion;
however, few patients with Wernicke’s syndrome display the
complete triad, and the diagnosis of Wernicke’s syndrome may be
missed in up to 90% of clinical presentations. Korsakoff’s
syndrome/psychosis, as mentioned earlier, is thought to occur after
an acute episode of Wernicke’s encephalopathy and may reflect the
long-term brain damage resulting from thiamine deficiency.
Essential management of Wernicke’s encephalopathy requires the
administration of high-dose intravenous thiamine as described
earlier.
Alcohol appears to be a potent cause of depressed mood in
some people. Patients who are intoxicated may appear severely
depressed and display suicidal behavior or statements that may
resolve when sobriety is achieved. Treatment of depression should
be geared to patients who remain depressed after 2 to 4 weeks of
sobriety. Anxiety is also common in patients who are withdrawing
or newly sober, and they should be assessed after at least 1 month
of sobriety. Inpatient and residential rehabilitation programs use a
team approach aimed at focusing the patient on recovery. Group
therapy allows patients to see their own problems mirrored in and
confronted by others. Family therapy allows the patient to examine
the role of the family in alcoholism.
PHARMACOLOGIC MANAGEMENT OF ALCOHOL USE

DISORDERS
The medications used to reduce drinking and increase sobriety for
alcohol use disorders are discussed in Chapter 19.
Naltrexone (Revia; Vivitrol) is a μ-opioid antagonist that blocks
the pleasurable effects of alcohol. Naltrexone reduces both the
amount of alcohol intake and the frequency of alcohol intake.
Naltrexone is usually dosed at 50 mg per day, but higher doses may
potentially be more effective. Unlike disulfiram (information to
follow), patients can continue taking naltrexone if they relapse to
alcohol intake. Naltrexone, as an opioid antagonist, may work in
part by reducing the reinforcing “high” of alcohol ingestion.
Acamprosate (Campral) is a glutamate receptor modulator (and
may also affect GABA) medication used for the maintenance of
alcohol abstinence and in reducing the rate and severity of relapse.
Like naltrexone, acamprosate does not produce a disulfiram-like
effect and can be continued in persons who relapse to alcohol
consumption.
Disulfiram (Antabuse) inhibits the second enzyme in the
pathway of alcohol metabolism, aldehyde dehydrogenase, causing
acetaldehyde to accumulate in the bloodstream. Symptoms of
increased acetaldehhyde include flushing, headache, sweating, dry
mouth, nausea, vomiting, and dizziness. In more severe reactions,
chest pain, dyspnea, hypotension, and confusion occur. In theory,
disulfiram should inhibit drinking by making it physiologically
unpleasant; however, because the effects can be fatal in rare cases,
patients must be committed to abstinence and fully understand the
danger of drinking while taking disulfiram. The usual dose of
disulfiram is 250 mg daily.
It is important to note that naltrexone, acamprosate, and
disulfiram are used for maintenance therapy to reduce or prevent
alcohol use. These agents do not prevent the potentially life-
threatening symptoms of alcohol withdrawal.
Many studies have demonstrated benefits from rehabilitation
programs, but nearly half of all treated alcohol-dependent patients
will relapse, most commonly in the first 6 months.
SEDATIVE-, HYPNOTIC-, OR ANXIOLYTIC-

RELATED DISORDERS
Sedative, hypnotic, and anxiolytic drugs are widely used. They are
all cross-tolerant with each other and with alcohol due to their
action at the GABA receptor (see Fig. 18-2). Included in this class
are barbiturates and benzodiazepines. Of these, the
benzodiazepines are the most widely prescribed and available.
Note that this section for sedative, hypnotic, and anxiolytic
drugs refers to only barbiturates and benzodiazepines that share in
common augmentation of GABA function. It is important to
differentiate these drugs from other drugs used for sleep induction
and from other medications used in psychiatry to treat anxiety. In
particular, serotonin reuptake inhibitor antidepressants and
buspirone are first-line treatments for some types of anxiety, but
they are not classified here. The barbiturate and benzodiazepines
can produce a life-threatening withdrawal syndrome when stopped
after a period of continuous administration.
EPIDEMIOLOGY
Approximately 15% of the general population is prescribed a
benzodiazepine in a given year. The rate of substance use disorders
related to benzodiazepines and barbiturates is 0.3%.
History
Sedative-hypnotic drugs are associated with syndromes of
intoxication, withdrawal, and withdrawal delirium that closely
resemble those of alcohol. These drugs are commonly combined
with alcohol, resulting in risk for life-threatening respiratory
depression. More recently, benzodiazepines have been increasingly
combined with opiates, raising the risk of respiratory depression
and death.
Physical and Mental Status Examinations

Sedative, hypnotic, or anxiolytic intoxication can be distinguished
from alcohol intoxication by the presence (or absence) of alcohol
on the breath, in the serum, or urine. Barbiturates, when taken
orally, are much more likely than benzodiazepines to cause
clinically significant respiratory compromise.
Laboratory Tests
Intoxication can be confirmed through quantitative or qualitative
serum or urine toxicologic analyses. Serum toxicologic screens can
identify the presence of benzodiazepines, barbiturates, and their
major metabolites. Withdrawal symptoms are listed in Table 10-5.
Withdrawal delirium (confusion, disorientation, and visual and
somatic hallucinations) has an onset as early as 3 to 4 days after
abstinence depending on the half-life of the drug in question.
TABLE 10-5. Signs and Symptoms of Sedative-Hypnotic
Withdrawal
Minor Withdrawal More Severe Withdrawal
Restlessness Coarse tremors
Apprehension Weakness
Anxiety Vomiting
Sweating
Hyperreflexia
Nausea
Orthostatic hypotension
Seizures
MANAGEMENT
Sedative-hypnotic withdrawal may be treated on an outpatient or an
inpatient basis. Outpatient treatment consists of gradually
decreasing the dose of the medication and requires a strong
commitment from the patient. Generally, inpatient detoxification is
required when there is comorbid medical or psychiatric illness,
prior treatment failures, history of complications such as seizures,
or lack of support by family or friends. On an inpatient unit,
benzodiazepines or barbiturates may be administered and tapered
in a controlled manner. Withdrawal from short-acting substances is
generally more severe, whereas withdrawal from longer acting
substances is more prolonged.
Withdrawal from barbiturates is more dangerous than that from
benzodiazepines, because it can more easily lead to hyperpyrexia,
seizure, and death. Withdrawal is managed by scheduled dosing
and tapering of a benzodiazepine or barbiturate (often diazepam or
phenobarbital).
In patients who have been abusing alcohol and benzodiazepines
or barbiturates, it may be necessary to perform a pentobarbital
challenge test. This test allows for the quantification of tolerance
to perform a controlled taper, thereby reducing the problems of
withdrawal. Once pentobarbital has been used to quantify the level
of tolerance, phenobarbital is dosed until sedation is achieved, then
the total dose is calculated and used as a starting point for gradual
taper over several days.
Treatment of sedative-hypnotic use disorder resembles that for
alcohol use disorder. After detoxification, the patient can enter a
residential rehabilitation program or a day or evening treatment
program. Referral to AA is appropriate because the addiction issues
and recovery process are similar.
OPIOID-RELATED DISORDERS
Opioids include naturally occurring drugs derived from opium
(opiates) as well as synthetically manufactured drugs designed to
mimic these substances. Commonly encountered opioids include
codeine, fentanyl, heroin, hydrocodone, hydromorphone
meperidine, morphine, and oxycodone. Heroin (diacetylmorphine)
is available only illegally in the United States. Opioids are
commonly used for control of acute and chronic pain.
EPIDEMIOLOGY
Opioid use has increased in the United States because of increasing
access to prescription pain relievers and increased attention to
monitoring pain as “the fifth vital sign.” In a national survey,
34.1% of respondents reports using a prescribed pain reliever in the
past 30 days, 4.3% reported misuse of these drugs, and 0.7%
reported symptoms that met criteria for a substance use disorder in
the past year. The percentage of respondents reporting past 30-day
heroin use was 0.2%; and 0.2% reported past year heroin use
disorder. Lifetime heroin use was reported by 1.8% of respondents.
The estimated lifetime prevalence of injection drug use in adults in
the United States is estimated to be 2.6%. The prevalence of use in
the past 30 days is estimated to be 0.3%.
History
An adequate history regarding opioid use requires enquiring about
misuse of prescription opioids. Patients with opioid use disorders
may acquire prescriptions from multiple sources. Misused
prescription opioids are most commonly acquired for free from a
relative or friend. Patients should be asked about route of
administration; and if injection use is acknowledged, patients
should be asked about potential contamination of needles by
sharing with others. Sharing needles carries high risk for viral
(human immunodeficiency virus [HIV], hepatitis C) or bacterial
infection. History of prior treatment including treatment with
substitution opioids such as methadone should also be acquired.
Physical and Mental Status Examinations

Signs of opioid intoxication include pupillary constriction,
respiratory depression, slurred speech, hypotension, bradycardia,
and hypothermia. The time course of intoxication is dependent on
the route of administration (intravenous > inhalation > oral).
Nausea, vomiting, and constipation are potential consequences of
opioid use.
Laboratory Tests
Opioid use can be confirmed by urine or serum toxicologic
measurements.
Opioid use disorder is defined by the criteria for substance
abuse previously noted. Withdrawal symptoms usually begin 10
hours after the last dose of short-acting medication. Withdrawal
from opioids can be highly uncomfortable, but is rarely medically
complicated or life-threatening. Withdrawal symptoms are listed in
Table 10-6.
TABLE 10-6. Symptoms of Opioid Withdrawal

Mild Withdrawal More SevereWithdrawal
Dysphoric mood, anxiety, Nausea
and restlessness Vomiting
Lacrimation or rhinorrhea Muscle aches
Pupillary dilatation Seizures (in meperidine
Piloerection withdrawal)
Sweating Abdominal cramps
Tachycardia Hypertension
Fever Hot and cold flashes
Diarrhea Severe anxiety
Insomnia
Yawning
Patients with opioid use disorders often have other comorbid

substance use disorders, antisocial personality disorder, and mood
disorders. Patients with opioid use disorders are more prone to
commit crimes because of the high cost of opioids. Opioid
addiction is also associated with high mortality rates from
inadvertent overdoses, accidents, and suicide. In addition, patients
with opioid use disorders are at higher risk of medical problems
because of poor nutrition and use of contaminated needles.
Common medical disorders in intravenous drug users include
hepatitis, HIV infection, endocarditis, pneumonia, and cellulitis.
The diagnosis of opioid use disorder includes physiologic
dependence as a result of prescribed opioid medication.
Nonpathologic physiologic dependence can be distinguished from
opioid use disorder with careful history as well as mental status and
physical examinations.
MANAGEMENT
Medical management of opioid use disorder typically involves
substitution of methadone or buprenorphine for the abused drug.
The substitution therapy can then be gradually withdrawn
(detoxification) or can be continued as maintenance treatment to
prevent relapse. Unlike withdrawal from alcohol and other central
nervous system (CNS) depressants, opioid withdrawal is not
associated with fatal outcomes.
Methadone, buprenorphine, and clonidine are also discussed in
Chapter 19. Methadone is a weak agonist of the μ-opioid receptor
and has some antagonist properties for the N-methyl-d-aspartate
(NMDA) receptor. Methadone has a longer half-life (15 hours)
than has heroin or morphine. Thus, it causes relatively few
intoxicant or withdrawal effects. Generally, the initial dose of
methadone (typically 5 to 20 mg) is based on the profile of
withdrawal symptoms. Withdrawal from short-acting opioids lasts
7 to 10 days; withdrawal from longer acting meperidine lasts 2 to 3
weeks.
Buprenorphine (Buprenex) is a μ-opioid receptor partial agonist
and a κ-opioid receptor antagonist. Injectable buprenorphine is
employed as an off-label use for opioid detoxification.
Buprenorphine tablets as buprenorphine alone (Subutex) or as
buprenorphine plus naloxone (Suboxone) are approved by the U.S.
Food and Drug Administration for outpatient treatment of opioid
dependence by certain qualified physicians. Approval of the tablet
form of buprenorphine permitted the expansion of the treatment of
opioid dependence beyond that of methadone clinics. Inclusion of
naloxone with buprenorphine in Suboxone allows the
administration of opioid replacement therapy with decreased
euphoric and respiratory depressant effects.
Clonidine, a centrally acting α-2 receptor agonist that decreases
central noradrenergic output, can also be used for acute withdrawal
syndromes. It is remarkably effective in treating the autonomic
symptoms of withdrawal, but does little to curb the drug craving.
Risks of sedation and hypotension limit the usefulness of clonidine
in outpatient settings. Clonidine does not appear to be as effective
as opioid replacement in helping maintain abstinence. Additional
medications can be used to relieve uncomfortable symptoms of
withdrawal, such as dicyclomine for abdominal cramping,
promethazine for nausea, and quinine for muscle aches.
CENTRAL NERVOUS SYSTEM STIMULANT

USE DISORDERS
Cocaine and amphetamines are readily available in the United
States. The patterns of use and abuse of and dependence on cocaine
and amphetamines are similar because both are CNS stimulants
with similar psychoactive and sympathomimetic effects.
In the United States, cocaine is available in two forms: as
cocaine hydrochloride powder, which is typically snorted and as
cocaine alkaloid crystal (“crack”), which is typically smoked.
Cocaine has an extremely rapid onset of action (when snorted or
smoked) and a short half-life, requiring frequent dosing to remain
“high.”
In the United States, an amphetamine (dextroamphetamine) and
a methylphenidate are available in pill form by prescription for the
treatment of obesity, narcolepsy, and attention-deficit/hyperactivity
disorder. Various forms of amphetamine are used illicitly including
a very pure form of methamphetamine, called crystal
methamphetamine, which can be snorted or smoked.
Amphetamines have a longer half-life than cocaine and hence are
taken less frequently.
Rates of depression are generally higher in individuals with
CNS stimulant use disorders. Antidepressant medications
influencing catecholamine function, such as desipramine and
bupropion, are generally superior to the selective serotonin
reuptake inhibitors in the treatment of cocaine-related depression.

INTOXICATION
Cocaine or amphetamine intoxication is characterized by the
following:
1. Maladaptive behavioral changes (e.g., euphoria or

hypervigilance)
2. Tachycardia or bradycardia
3. Pupillary dilatation
4. Hyper- or hypotension
5. Perspiration or chills
6. Nausea or vomiting
7. Psychomotor agitation or retardation
8. Muscular weakness, respiratory depression, chest pain, cardiac
dysrhythmias
9. Confusion, seizures, dyskinesia, or coma
Cocaine intoxication can cause tactile hallucinations (coke

bugs). Both cocaine and amphetamine intoxication can lead to
agitation, impaired judgment, and transient psychosis (e.g.,
paranoia, visual hallucinations). Cocaine and amphetamine
dependence is defined by the criteria outlined for substance
dependence.

WITHDRAWAL
Withdrawal of cocaine or amphetamines leads to fatigue,
depression, nightmares, headache, profuse sweating, muscle
cramps, and hunger. Withdrawal symptoms peak in 2 to 4 days.
Management
Withdrawal from amphetamines or other CNS stimulants is self-
limited and usually does not require inpatient detoxification.
Psychosis from amphetamine intoxication or withdrawal is
generally self-limited, requiring only observation in a safe
environment. Antipsychotic medications can be used to treat
agitation.
Ultimately, the goal is rehabilitation. Narcotics Anonymous,
treatment of comorbid psychopathology, administration of drugs to
reduce craving, and family therapy are the essential features of
cocaine rehabilitation.
CANNABIS-RELATED DISORDERS
Cannabis is the most widely used recreational drug throughout the
world in the forms of marijuana and hashish. The drug is usually
smoked and causes a state of euphoria. Complications of cannabis
use include impaired judgment, poor concentration, and poor
memory. Serious complications include delirium and psychosis.
Signs of chronic cannabis use include yellowing of the fingers,
characteristic odor on clothing, use of incense to cover the odor,
and chronic cough.
CANNABIS USE DISORDER
Epidemiology
Twelve-month prevalence of cannabis use disorder is about 3.4 %
in youth aged 12 to 17 years and 1.5% in adults aged 18 years and
older.
A prominent feature of cannabis use disorder is a lack of
motivation that is often not of concern to the individual, but causes
concern in parents or loved ones who urge the patient to seek
treatment.
Laboratory Tests
In chronic users of cannabis, urine toxicology tests can remain
positive for over a month, making these an unreliable indicator of
abstinence. Toxicology of hair samples can provide a more
accurate indication of cannabis use over time.
The differential diagnosis for cannabis use disorder includes
nonproblematic use of cannabis as well as depression or anxiety
disorders.
Management
There are no pharmacologic interventions for cannabis use
disorder. Treatment of comorbid medical and psychiatric
conditions may improve abstinence. Cognitive behavioral therapy
has been found to decrease cannabis use in teens.
CANNABIS INTOXICATION
Signs of cannabis intoxication include impaired motor
coordination, euphoria, anxiety, sensation of slowed time, impaired
judgment, social withdrawal, conjunctival injection, increased
appetite, dry mouth, and tachycardia.
CANNABIS WITHDRAWAL
Cannabis withdrawal syndromes are self-limited and do not require
psychiatric or medical treatment.
OTHER SUBSTANCES
CLUB DRUGS
Club drugs are a group of drugs classified by the U.S. National
Institute on Drug Abuse according to their popularity in dance
clubs and other party venues. These drugs are of a wide variety of
chemical classes, but are linked by their frequent use in social
groups and the fact that they are commonly taken together. Because
of their popularity and tendency for users to show up in emergency
rooms, the following information reviews some of the more widely
used club drugs. It is important to note that drug use trends can
change rapidly, and existing drugs may go in or out of fashion.
New drugs may also emerge at any time.
3,4-Methylenedioxymethamphetamine
3,4-Methylenedioxymethamphetamine (MDMA) is a widely
popular drug sold as ecstasy or Molly and has mixed stimulant and
hallucinogenic properties. Many users report a stimulant and
euphoric effect, and MDMA appears specifically to enhance the
user’s desire for intimacy with others. As such, its use has been
associated with an increased frequency of unsafe sexual activity.
Acute use of MDMA has been associated with deaths from various
causes. Long-term MDMA use leads to a long-lasting reduction in
serotonin transmission throughout the neocortex; and MDMA use
has been associated with increased suicidal thinking, sleep apnea,
and altered pain response.
Methamphetamine
Also known as crystal or crank, methamphetamine is a
psychostimulant that is neurotoxic to dopamine and serotonin
axons. Methamphetamine is often produced locally in small
laboratories and can therefore vary greatly in purity. The latest
survey results from the U.S. National Survey on Drug Use and
Health indicate that about 5% to 6% of people have used
methamphetamine in their lifetime, with rates greatest in the 18- to
25-year-old age group. Consistent with its dopamine neurotoxicity,
methamphetamine use has been associated with increased rates of
Parkinson’s disease.
γ-Hydroxybutyrate
γ-Hydroxybutyrate (GHB) is a compound used in lower doses by
bodybuilders and others seeking to gain muscle mass (GHB
promotes the release of growth hormone). In higher doses, GHB is
used to produce a high and is common among the club and party
scene. GHB is easily overdosed and can lead to death from
respiratory arrest. GHB dependence may occur, and withdrawal
requires medical management.
Ketamine
Also known as Special K, ketamine is a dissociative anesthetic
mostly used in veterinary medicine. It is used for its hallucinatory,
dissociative effect. Ketamine has also shown promise in treating
depression and suicidal ideation.
Rohypnol
Rohypnol is a benzodiazepine approved for clinical use in some
countries outside the United States. Rohypnol produces classic
benzodiazepine effects of sedation. It has strong amnestic
properties, however, and it may be a frequent culprit in drugging
others for the purpose of theft or sexual assault.
Lysergic Acid Diethylamide

Lysergic acid diethylamide (LSD) is famous for its hallucinogenic
properties. Acute use can produce a highly euphoric (good trip) or
a highly dysphoric (bad trip) hallucinatory experience. Long-term
LSD use can lead to psychosis or hallucinogen persisting
perception disorder.
KEY POINTS
In alcohol use disorders, denial and minimization
are common.
Benzodiazepines are used in acute detoxification
from alcohol to prevent life-threatening
complications of withdrawal.
Peak incidence of alcohol withdrawal seizures is
within 12 to 24 hours.
Rehabilitation, involving AA and therapy, is aimed
at abstinence and treating comorbid disorders.
Wernicke’s triad, although seen in a minority of
cases, consists of nystagmus, ataxia, and mental
confusion.
Alcohol-induced persisting amnestic disorder
(Korsakoff’s) symptoms result from brain damage
due to thiamine deficiency and include amnesia
and confabulation.
Sedatives and hypnotic drugs are cross-tolerant
with alcohol, and withdrawal states are similar to
that of alcohol.
Opioid use disorder increases the risk of human
immunodeficiency virus, pneumonia, endocarditis,
hepatitis, and cellulitis with high mortality rates
from accidental overdose, suicide, and accidents.
Opioid withdrawal is uncomfortable but not usually
medically complicated.
Cocaine and amphetamines are CNS stimulants
and can cause transient psychosis (e.g., coke
bugs or paranoia).
Stimulant withdrawal symptoms (fatigue,
depression, nightmares, etc.) are self-limited and
peak in 2 to 4 days.
CLINICAL VIGNETTES
VIGNETTE 1
A 57-year-old man with a medical history of “liver problems” is seen in
psychiatric consultation in the hospital intensive care unit because of
agitation and confusion. The available history indicates that the patient
was involved in a motor vehicle accident 72 hours ago in which he
sustained a tibial fracture requiring emergent surgical procedures for
repair. The patient suffered no head injury or loss of consciousness
during the accident but was sedated after surgery. His medications
since arriving in the hospital have included only antibiotics and opiate
pain relievers.
1. The diagnosis most consistent with agitation and confusion in this
patient is:
a. Dementia
b. Psychotic disorder
c. Delirium
d. Antisocial personality disorder
e. Akathisia
2. The laboratory results for the patient include elevations in multiple

liver enzymes with moderate anemia, leukopenia, and
thrombocytopenia. A potentially critical treatment or diagnostic
intervention at this point would include:
a. Transfusion of packed red blood cells
b. Evaluation for pulmonary embolism
c. Administration of an antidepressant medication
d. Administration of intravenous thiamine
e. Increase in the dosage of opiate pain reliever
3. Additional history obtained from the above patient’s family

indicates that he drinks alcohol on a daily basis. His minimum
daily consumption of alcohol consists of a 12-pack of regular
beer, but he often consumes more than twice that amount. The
patient’s vital signs reveal a heart rate of 130 beats per minute
and a blood pressure of 180/110 mm Hg. An additional critical
treatment at this point would include:
a. Buspirone to treat withdrawal symptoms
b. Propanolol to treat hypertension and tachycardia
c. Intravenous hydration to treat tachycardia
d. A benzodiazepine to treat withdrawal symptoms
e. Clonidine to treat hypertension
4. The patient responds to treatment, and his confusion and

autonomic instability resolve. He is successfully tapered from
benzodiazepines and has not required opiate pain relievers for
the past 7 days. He expresses a desire to stop drinking alcohol
and requests treatment for alcohol dependence. An appropriate
pharmacologic intervention might include:
a. An antidepressant medication of the selective serotonin-
reuptake inhibitor class
b. A benzodiazepine medication
c. An antihypertensive medication
d. An opiate analgesic medication
e. Naltrexone
VIGNETTE 2
A 27-year-old nurse appears in your private practice office
complaining of recurrent back pain. On examination, the patient is
noted to have a runny nose, dilated pupils, piloerection, mild fever,
and mild tachycardia. The patient reports that she has previously used
oxycodone for her back pain for brief periods but has not used any
pain relievers for several months. She states that she has back
problems “about twice a year.” You obtain an additional laboratory
test, make a diagnosis, and prescribe treatment for this patient. A
week later, you are the emergency ward attending physician when the
patient is brought in by ambulance; she is unconscious with very slow
respirations and mild perioral cyanosis.
1. The best emergency treatment for this patient is:

a. Flumazenil
b. Physostigmine
c. Clonidine
d. Acamprosate
e. Naloxone
f. Diazepam
g. Thiamine
h. Glucose
2. Because of its long half-life, the following drug is commonly used

as a maintenance medication for individuals with opioid
dependence. It is a weak agonist at the μ-opiate receptor and has
a half-life of 15 hours. The drug is administered in government-
licensed clinics. The goal is to alleviate drug hunger and minimize
drug-seeking behavior. The drug described is:
a. Heroin
b. Morphine
c. Methadone
d. Hydrocodone
e. Hydromorphone
3. After learning about methadone, the patient asks if there are

alternative maintenance medications for opioid use
disorder/opioid dependence. Which of the following medications
would be appropriate?
a. Flumazenil
b. Morphine
c. Naltrexone
d. Naloxone
e. Buprenorphine plus naloxone
VIGNETTE 3
A 43-year-old male is admitted to the hospital for a leg fracture
sustained after falling from a ladder while intoxicated with alcohol. He
reports a history of daily alcohol use since the age of 9 years except
for rare periods of sobriety during brief stints in jail or in hospitals. He
denies any period of sustained depression or symptoms suggestive of
mania or hypomania. He is currently taking opiate pain relievers for
leg pain and is receiving thiamine, folate, and benzodiazepines for
alcohol withdrawal.
1. Appropriate management at this point would include:

a. Continue his current treatment regimen with downward
adjustments in opiate and benzodiazepine dosing as pain and
alcohol withdrawal symptoms subside.
b. Add naltrexone to his current treatment regimen to treat alcohol
dependence.
c. Stop opiate pain relievers because he may become addicted to
them.
d. Stop benzodiazepines because he may become addicted to
them.
e. Add an antidepressant medication to his current treatment
regimen.
2. The patient recovers nicely from his fracture and has a successful
detoxification from alcohol. He has not required opiate pain
relievers or benzodiazepines for the past week. The patient
expresses an interest in future treatment options for alcohol
dependence/alcohol use disorder. The best treatment
recommendation would include:
a. Alcoholics Anonymous, cognitive-behavioral therapy, and
naltrexone
b. Naltrexone monotherapy
c. Cognitive-behavioral therapy
d. Alcoholics Anonymous
e. Duloxetine monotherapy
f. Oxazepam monotherapy
g. Acamprosate monotherapy
VIGNETTE 4
A 29-year-old man is dropped off by friends at the emergency
department. The patient complains of chest pain. On examination, he
is nervous, diaphoretic, and pacing. His vital signs indicate a heart
rate of 132 beats per minute with a blood pressure of 175/100 mm Hg.
The patient is afebrile. An electrocardiogram reveals sinus tachycardia
with ST-segment depressions in the anterior leads. The patient
smokes 1.5 packs of cigarettes per day. He does not recall a prior
diagnosis of hypertension, hypercholesterolemia, or diabetes. He has
no known prior history of “heart trouble” and denies alcohol or drug
use.
1. After electrocardiogram and laboratory tests to evaluate for

myocardial infarction, an essential diagnostic test at this point is:
a. Abdominal ultrasound
b. Electroencephalogram
c. Urine drug screen
d. Hematocrit
e. Liver function tests
2. A urine test obtained on the patient reveals cocaine and cocaine

metabolites in the urine specimen. The patient has a mild
myocardial infarction without significant arrhythmia or other
complications. On confrontation, he states that he rarely uses
cocaine, and this was the first time in many months. On checking
the patient’s chart from prior visits, however, it is clear that the
patient has had several emergency ward visits for chest pain with
cocaine-positive urine tests over the last year. After further
discussion, the patient admits that he has had escalating cocaine
use for several years, requiring more cocaine to feel “high,” has
lost multiple jobs because of cocaine use, has had recurrent legal
complications, and has been unable to quit or reduce cocaine
intake despite his best efforts. At this point, you can make the
following diagnosis with confidence:
a. Polydrug abuse
b. Antisocial personality disorder
c. Cocaine use disorder
d. Coronary artery disease
e. Malingering
ANSWERS
1. Answer C:
Relatively acute-onset agitation and confusion in the intensive care
unit setting are commonly caused by delirium. A psychotic disorder
can be associated with agitation, but no history of psychotic symptoms
is provided. Dementia is a risk factor for the development of delirium,
but the onset of dementia is usually quite gradual, is not part of the
patient’s prior history, and would be uncommon in this age group.
Antisocial personality disorder is associated with traits that might
include agitation or threatening behavior, but antisocial personality
disorder is not directly associated with confusion. Akathisia resulting
from medication administration, especially administration of typical
antipsychotics (neuroleptics), is a common cause of agitation but not
confusion in the intensive care unit setting. Opiates and antibiotics are
not likely to produce akathisia.
2. Answer D:
An all-too-common cause of delirium in the intensive care unit setting,
especially following traumatic injury, is the presence of alcohol
withdrawal delirium potentially complicated by Wernicke’s
encephalopathy, a major neurocognitive disorder. Alcohol use can be
associated with accidents, including motor vehicle accidents that
result in emergency hospitalizations. The elevations in liver enzymes
coupled with a relative pancytopenia and a history of liver problems is
consistent with a diagnosis of alcohol dependence, although other
medical causes of these findings should be ruled out. Administration
of intravenous thiamine is a critical treatment to prevent the
development of irreversible brain damage as seen in Wernicke’s
encephalopathy and so the risk/benefit of providing this treatment until
more details are obtained is favorable.
3. Answer D:
At this point, the primary diagnostic consideration is alcohol
withdrawal delirium. Patients may either be unable or unwilling to
report alcohol use history and are at risk for withdrawal delirium if their
alcohol use history is not identified. Alcohol withdrawal delirium is a
life-threatening complication of untreated alcohol withdrawal that
typically starts 48 to 72 hours after abrupt cessation of alcohol intake
in alcohol-dependent individuals. The patient has elevated heart rate,
blood pressure, and body temperature symptoms consistent with
sympathetic hyperarousal. The treatment of choice is a
benzodiazepine medication to prevent further deterioration and
prevent seizure. Buspirone is a medication approved for generalized
anxiety, but it does not treat sympathetic hyperarousal. Propanolol
alone or clonidine alone might reduce aspects of sympathetic
activation (heart rate and blood pressure) but would actually mask the
severity of the withdrawal and would not help to prevent seizure.
Intravenous hydration, along with supplementation of magnesium,
folate, and thiamine, is often an important supportive treatment in
alcohol withdrawal but does not treat the life-threatening symptoms of
seizure and autonomic hyperarousal.
4. Answer E:
Naltrexone is an opiate antagonist medication that is approved for use
in alcohol dependence (severe alcohol use disorder). Naltrexone does
not treat alcohol withdrawal, but it does help reduce alcohol intake.
Naltrexone as a pharmacologic treatment should be combined with
psychosocial treatments such as attendance at Alcoholics Anonymous
and participation in psychotherapy. Naltrexone should not be used in
patients who continue to take opiate pain relievers because the
medication will precipitate acute opiate withdrawal. Benzodiazepine
medications are indicated in the treatment of alcohol withdrawal but
have a high risk of abuse and are generally not indicated for
postdetoxification treatment. Antidepressant medications may be
important adjunct therapy in individuals who have depression that
persists after alcohol detoxification but are not generally indicated for
treating alcohol abuse or dependence. An antihypertensive medication
might be appropriate if a patient has persistently elevated blood
pressure following alcohol detoxification, but many individuals in acute
alcohol withdrawal have markedly elevated blood pressure that
normalizes after detoxification. An opiate analgesic medication is not
indicated because the patient has already been tapered from opiate
analgesics, suggesting that he no longer requires opiates for acute
pain relief.
1. Answer E:
While more history is needed, the patient likely has opioid
dependence/opiate use disorder and at this point is most likely
suffering from an opioid overdose. The symptoms of lacrimation,
dilated pupils, piloerection, mild fever, and mild tachycardia present at
the patient’s initial outpatient presentation are consistent with opioid
withdrawal. The laboratory test you ordered was a urine drug screen
that was positive for opioid metabolites. After confrontation during the
initial visit, the patient confessed that she had sought opiate
prescriptions from multiple physicians and had also been stealing
narcotics from the hospital by pretending to give them to patients and
then pocketing them. You had prescribed an inpatient admission for
opiate detoxification followed by outpatient psychotherapy and self-
help group involvement. The patient had successfully detoxified before
being found unresponsive. Of the listed treatments, flumazenil is a
benzodiazepine antagonist at the γ-aminobutyric acid (GABA)
receptor and is useful for reversing benzodiazepine-induced sedation
or benzodiazepine overdose. Physostigmine is a cholinesterase
inhibitor that is helpful in treating anticholinergic toxicity. Clonidine is
an α-2 adrenoreceptor agonist that may help with symptoms of opiate
withdrawal but not with opiate intoxication. Acamprosate is useful in
the treatment of alcoholism. Naloxone is an opiate antagonist that can
be life-saving in cases of opiate overdose. Diazepam is a
benzodiazepine that is useful in alcohol withdrawal. Thiamine and
glucose are important treatments in patients who are found
unresponsive and would also be important in the management of this
patient in case other factors were contributing to the diagnosis.
2. Answer C:
Methadone maintenance is a method of long-term treatment of illicit
opioid abuse (primarily heroin but also abuse of illicitly obtained
prescription opioids). It involves administration of a single daily dose of
the long-acting opioid in a controlled setting along with provision of
counseling and social services; supportive services are vital to the
success of a methadone maintenance program. Methadone
maintenance reduces and often eliminates use of nonprescribed
opioids, decreases criminal activity associated with illicit drug use, and
reduces the spread of HIV. Heroin, morphine, hydrocodone, and
hydromorphone are opioids but are not used as maintenance therapy
to treat opioid dependence. Morphine, hydrocodone, and
hydromorphone are prescription analgesics that are often abused.
3. Answer E:
The best choice is buprenorphine with naloxone (brand name
Suboxone). Buprenorphine, a partial opioid agonist, reduces illicit
opioid use with long-term therapy. Naloxone is an opioid antagonist
that has poor oral absorption. When used alone, buprenorphine does
have the potential to be abused as an injectable agent. When
buprenorphine is combined with naloxone; however, it will cause
withdrawal when given parenterally but not when given orally because
of the poor oral absorption of naloxone. Flumazenil is a
benzodiazepine antagonist at the GABA receptor and is used for
treating benzodiazepine overdose. Morphine is a short-acting opiate
that is not appropriate for maintenance therapy. Naltrexone is an
opiate antagonist, and although it may help reduce craving in opioid
dependence, it is not an opioid replacement therapy.
1. Answer A:
Continue the patient’s current treatment regimen with downward
adjustments in opiate and benzodiazepine dosing as pain and alcohol
withdrawal symptoms subside. Gradual taper of opiate pain
medication with clinical improvement and gradual taper of
benzodiazepines with improved symptoms of alcohol withdrawal are
the appropriate treatment at this point. Naltrexone is indicated for
treating alcohol dependence but should not be given to a person
taking opiates because it may precipitate severe withdrawal. Judicious
use of opiates is necessary in many drug- or alcohol-dependent
individuals in circumstances normally requiring treatment with opiate
medications, such as following injury or surgery. Benzodiazepines,
although potentially addictive, are used for the short-term treatment of
alcohol withdrawal symptoms and should be slowly tapered to avoid
precipitating a seizure or other severe withdrawal symptoms.
Antidepressant medications may be useful in individuals with alcohol
dependence and depression, but the provided history is not
suggestive of depression in this patient.
2. Answer A:
Following successful alcohol detoxification, combined treatment with
Alcoholics Anonymous, cognitive-behavioral therapy, and
pharmacologic management with naltrexone or acamprosate is
indicated. Naltrexone, cognitive-behavioral therapy, attending
Alcoholics Anonymous meetings, or acamprosate alone would also be
useful treatments but are not as effective individually as is
combination therapy. The exact mechanism of naltrexone in
preventing or lessening the severity of alcohol relapse is unknown but
is presumably related to the action of naltrexone as a μ-opioid
antagonist. Acamprosate may work via numerous mechanisms,
including as a modulator of glutamate function. Duloxetine is an
antidepressant that might be used in treating the patient if he had
major depression. Oxazepam is used for acute detoxification for
alcohol dependence but is contraindicated after detoxification, as it
may precipitate relapse or lead to oxazepam abuse or dependence in
alcoholism.
1. Answer C:
The patient’s symptom complex is consistent with that of intoxication
with psychostimulant drugs such as cocaine. The patient likely has
myocardial ischemia caused by cocaine-induced coronary artery
vasospasm. The patient is at risk for myocardial infarction, cardiac
arrhythmia, or stroke. In a patient who presents with this symptom
complex, it is most important to treat the patient as any other patient
with an acute myocardial infarction or acute myocardial ischemia
depending on the electrocardiogram and other findings. Ruling out
drugs of abuse as a cause of this event is critical to future treatment
and monitoring of this patient, however. An abdominal ultrasound is
not likely to be of use unless the patient complains of abdominal pain
or other signs suggesting splenic infarction or abdominal aneurysm
rupture. An electroencephalogram is unlikely to be of use in an alert
patient who has no evidence of altered mental status or headache.
Hematocrit will not substantially aid in the immediate diagnosis of the
patient’s condition. Liver function tests might be of use in such a
patient if there are risk factors for alcoholic hepatitis or viral hepatitis,
but they are not critical to the current diagnosis.
2. Answer D:
At present, the only diagnosis that can be made with confidence is
that of cocaine use disorder. The patient may have underlying
coronary artery disease but we are not provided with results of
diagnostic tests to support that conclusion and myocardial infarction
following cocaine use can be due to vasospasm. To make a diagnosis
of cocaine use disorder, however, one would need to know that the
patient had at least three symptoms consistent with tolerance,
withdrawal, repeated unintended excessive use, persistent failed
efforts to cut down, excessive time spent trying to obtain the
substance, cocaine-related reductions in social, occupational, or
recreational activities, and continued use despite awareness that
cocaine is causing psychological or physical difficulties. Because this
patient presented on multiple occasions to the emergency ward with
chest pain following cocaine use, he is probably aware of the
association between use of the drug and chest pain, and he would
therefore meet the last criterion (awareness of physical difficulties).
Polydrug abuse or at least polydrug exposure might also be found in
this patient, but the current evidence does not yet support that
diagnosis. Antisocial personality disorder requires a consistent and
sustained pattern of disregard for social rules. This patient may have
engaged in illegal activity, but this is common among cocaine users in
the absence of antisocial personality disorder. Malingering is
diagnosed when a person deceives to obtain secondary gain. Denial
of drug use is remarkably common among individuals with substance
use disorder and is not necessarily a symptom of malingering.
Ten types of personality disorders are grouped into clusters on the
basis of similar overall characteristics. There are three recognized
personality disorder clusters: odd and eccentric, dramatic and
emotional, and anxious and fearful (Table 11-1).
TABLE 11-1. Classification of Personality Disorders

Cluster A Cluster B Cluster C
(Odd/Eccentric) (Dramatic/Emotional) (Anxious/Fearful)
Paranoid Antisocial Avoidant
Schizoid Borderline Dependent
Schizotypal Histrionic Obsessive–
compulsive
Narcissistic
Diagnostic and Statistical Manual of Mental Disorders, 5th

edition (DSM-5) general diagnostic criteria for personality
disorders are outlined in Table 11-2. Criteria for individual
personality disorders are discussed later. Personality disorders
frequently overlap in symptoms.
TABLE 11-2. Diagnostic Criteria for Personality Disorders

Patients with personality disorder evidence an enduring pattern of inner
experience and behavior, established by adolescence or early adulthood,
that are characterized by the following:
1. Deviates markedly from cultural expectations
2. Is inflexible and personally and socially pervasive
3. Causes distress or social or work impairment
4. Is a stable pattern of experience and behavior of long duration (“stably
unstable”)
5. Cannot be explained by another mental illness
6. Is not caused by substance use or medical condition
Table 11-3 indicates the primary ego defense mechanisms (see

Chapter 21 on Psychological Theory for discussion of ego defense
mechanisms) found in a subset of personality disorders. However,
an individual may use multiple defense mechanisms.
TABLE 11-3. Primary Ego Defense Mechanisms in Some

Personality Disorders
Disorder Defense
Paranoid personality disorder Projection
Schizoid personality disorder Fantasy
Borderline personality disorder Splitting; acting out
Histrionic personality disorder Dissociation
Obsessive–compulsive Isolation
personality disorder
NEURAL BASIS
Scientifically grounded theories have emphasized the role of
neurobiology and evolutionary psychology in personality disorders.
Current evidence supports an interaction of genetics and
environment in producing personality. Although the DSM-5 criteria
for personality disorders are categoric, much contemporary
research approaches them as dimensional; and DSM-5 also includes
a dimensional approach. Some theorists consider fear and anger
traits as the core dysregulated emotions in personality disorders.
Others embrace more dimensions of personality structure including
affective instability, impulsivity, aggression, anxiety, and cognitive
factors. As a useful mnemonic, it is helpful to consider the origins
of particular symptoms, such as fear, anger, anxiety, and aggression
as having their roots in ancient neural structures related to the
limbic system (especially the amygdala, hippocampus, and
cingulate gyrus) (Fig. 11-1) and the monoamine neurotransmitters
(serotonin, dopamine, and norepinephrine) with the expression of
those symptoms modulated by more recently evolved brain regions
such as the neocortex and neurotransmitters such as γ-aminobutyric
acid and glutamate. Studies of the neurobiology of personality
disorders have begun to reveal structural and functional alterations
in these limbic brain regions. In borderline personality disorder, for
example, emerging evidence indicates reduced brain volume in
limbic structures.
FIGURE 11-1. Limbic system neuroanatomy. Major limbic system
structures involved in mediating many brain functions and whose
dysregulation is implicated in psychiatric disorders, including
personality disorders. The amygdala, hippocampal formation,
cingulate gyrus, and interconnected structures are important in many
components of personality disorders, especially those characterized
by anxiety, fear, anger, and aggression. Monoamine neurotransmitters
innervating these brain regions also play a major role in psychiatric
conditions and personality disorders. (Adapted from Hendelman WJ.
Student’s Atlas of Neuroanatomy. Philadelphia, PA: WB Saunders,
1994:179.)
CLUSTER A (ODD AND ECCENTRIC)
PARANOID PERSONALITY DISORDER

People with paranoid personality disorder are distrustful,
suspicious, and anticipate harm and betrayal.
Epidemiology
Paranoid personality disorder has a lifetime prevalence of 2% to
4% of the general population. Relatives of patients with chronic
schizophrenia and patients with persecutory delusional disorders
show an increased prevalence of paranoid personality disorder.
Etiology
Environmental precursors are unclear. Family studies suggest a link
to delusional disorder (paranoid type). There appears to be a small
increase in prevalence among relatives of individuals with
schizophrenia.
People with paranoid personality disorder are distrustful,
suspicious, and see the world as malevolent. They anticipate harm,
betrayal, and deception. Not surprisingly, they are not forthcoming
about themselves. They require emotional distance.
The key distinction is to separate paranoia associated with
psychotic disorders from paranoid personality disorder, especially
because paranoia associated with psychotic disorders is generally
responsive to antipsychotic medications.
SCHIZOID PERSONALITY DISORDER

Individuals with schizoid personality disorder are emotionally
detached and prefer to be left alone.
Epidemiology
Estimates of lifetime prevalence range as high as 3% to 5% of the
general population; but because people with schizoid personality
disorder are avoidant of others, they are not commonly seen in
clinical practice.
Etiology
There is some evidence to suggest increased prevalence of schizoid
personality disorder in relatives of persons with schizophrenia or
schizotypal personality disorder.
These people are loners. They are aloof and detached and have
profound difficulty experiencing or expressing emotion. Although
they prefer to be left alone and generally do not seek relationships,
they may maintain an important bond with a family member.
Schizoid personality disorder can be distinguished from avoidant
personality disorder (see later) and social phobia by the fact that
schizoid individuals do not desire relationships. Avoidant and
socially phobic persons desire and may seek relationships, but their
anxiety handicaps their capacity to achieve relatedness.
Schizophrenia and autism spectrum disorder are also differential
diagnostic conditions.
SCHIZOTYPAL PERSONALITY DISORDER

Individuals with schizotypal personality disorder have odd
thoughts, affects, perceptions, and beliefs.
Epidemiology
Lifetime prevalence is 3% to 4% of the general population.
Etiology
Studies demonstrate interfamilial aggregation of this disorder,
especially among first-degree relatives of individuals with
schizophrenia.
Schizotypal personality disorder is best thought of as similar to
schizophrenia but less severe and without sustained psychotic
symptoms. People with this disorder have few relationships and
demonstrate oddities of thought, affect, perception, and belief.
Many are highly distrustful and often paranoid, which results in a
very constricted social world.
Schizophrenia, delusional disorder, and mood disorder with
psychosis are the major differential diagnoses.
CLUSTER B (DRAMATIC AND EMOTIONAL)
ANTISOCIAL PERSONALITY DISORDER

Individuals with antisocial personality disorder (ASP) repetitively
disregard the rules and laws of society and rarely experience
remorse for their actions. The DSM-5 criteria require that a person
be at least 18 years old for a diagnosis of ASP and that some
symptoms of conduct disorder had to occur before age 15.
Epidemiology
ASP is present in 3% of men and in 1% of women. About half have
been arrested; about half of those in prison have ASP.
Etiology
ASP is more common among first-degree relatives of those
diagnosed with ASP. In families of an individual with ASP, men
show higher rates of ASP and substance abuse, whereas women
have higher rates of somatic symptom disorder. A harsh, violent,
and criminal environment also predisposes people to this disorder.
Individuals with ASP display either a flagrant or well-concealed
disregard for the rules and laws of society. They are exploitative,
lie frequently, endanger others, are impulsive and aggressive, and
rarely experience remorse for the harm they cause others. Alcohol
use disorder is a frequently associated finding in this population.
Many individuals with ASP are indicted or jailed for their actions.
Bipolar disorder and substance abuse disorder can be associated
with antisocial behaviors during the acute illness, but remit when
the disorder is controlled in those without comorbid ASP. The
antisocial behavior of individuals with ASP, conversely, is not state
dependent.
BORDERLINE PERSONALITY DISORDER

Individuals with borderline personality disorder suffer from
instability in relationships, self-image, affect, and impulse control.
Epidemiology
Lifetime prevalence is up to 6% of the general population, but up to
20% in psychiatric inpatient settings. The disorder is more common
in females, with a ratio of about 3 females:1 male.
Etiology
Borderline personality disorder is about five times as common
among first-degree relatives of patients with borderline personality
disorder. In addition, this disorder shows increased rates in families
with alcohol use disorders and families of individuals with ASP, as
well as in families with depressive or bipolar disorders. Abuse or
severe neglect in childhood increases the risk for the disorder.
Individuals with borderline personality disorder suffer from a
legion of symptoms. Their relationships are infused with anger,
fear of abandonment, and shifting idealization and devaluation.
Their self-image is inchoate, fragmented, and unstable with
consequent unpredictable changes in relationships, goals, and
values. They are affectively unstable and reactive, with anger,
depression, and panic prominent. Their impulsiveness can result in
many unsafe behaviors, including drug use, promiscuity, gambling,
and other risk-taking behavior. Their self-destructive urges result in
frequent suicidal and parasuicidal behavior (such as superficial
cutting or burning or nonfatal overdoses in which the intent is not
lethal). They also demonstrate brief paranoia and dissociative
symptoms. Suicide attempts can be frequent before the age of 30,
and suicide rates approach 10% over a lifetime. The principal
intrapsychic defenses such individuals use are denial, distortion,
projection, and splitting. Patients may exhibit a broad range of
comorbid illnesses, including substance use disorders, depressive
disorders, bipolar disorders, and eating disorders.
Mood disorders and behavioral changes resulting from active
substance use are the principal differential diagnostic
considerations. The diagnostic clues are unstable relationships,
unstable self-image, unstable affect, and unstable or impulsive
behaviors.
HISTRIONIC PERSONALITY DISORDER

Individuals with histrionic personality disorder have excessive
superficial emotionality and a powerful need for attention.
Epidemiology
Lifetime prevalence is 2% of the general population. In clinical
settings, the diagnosis is most frequently applied to women, but
may equally affect men in the general population.
Etiology
There appears to be a familial link to somatization disorder and to
ASP.
Individuals with histrionic personality disorder are characterized by
their excessive and superficial emotionality and their profound
need to be the center of attention at all times. Theatrical behavior
dominates with lively and dramatic clothing, exaggerated
emotional responses to seemingly insignificant events, and
inappropriate flirtatious and seductive behavior across a wide
variety of circumstances. Despite their apparent plethora of
emotion, these individuals often have difficulty with intimacy,
frequently believing their relationships are more intimate than they
actually are.
Somatic symptom disorder is the principal differential diagnostic
consideration.
NARCISSISTIC PERSONALITY DISORDER

Individuals with narcissistic personality disorder appear arrogant
and entitled but suffer from extremely low self-esteem.
Epidemiology
Lifetime prevalence is estimated at 1% to 6% in the general
population. Fifty percent to 75% of those with this diagnosis are
men.
Etiology
The etiology of this disorder is unknown.
People with narcissistic personality disorder demonstrate an
apparently paradoxic combination of self-centeredness and
worthlessness. Their sense of self-importance is generally
extravagant, and they demand attention and admiration. Concern or
empathy for others is typically absent. They often appear arrogant,
exploitative, and entitled. Despite their inflated sense of self,
however, below their brittle facade lies low self-esteem and intense
envy of those whom they regard as more desirable, worthy, or able.
The grandiosity of narcissism can be differentiated from the
grandiosity of bipolar disorder by the presence of characteristic
mood symptoms in bipolar disorder.
CLUSTER C (ANXIOUS AND FEARFUL)
AVOIDANT PERSONALITY DISORDER

Individuals with avoidant personality disorder desire relationships,
but avoid them because of the anxiety produced by their sense of
inadequacy.
Epidemiology
Lifetime prevalence is 2% to 3% of the general population and
appears to be equally prevalent in men and women.
Etiology
There are no conclusive data. The pattern of avoidance may start in
infancy.
People with avoidant personality disorder experience intense
feelings of inadequacy. They are painfully sensitive to criticism, so
much so that they are compelled to avoid spending time with
people. Their fears of rejection and humiliation are so powerful that
to engage in a relationship, they seek strong guarantees of
acceptance. The essence of this disorder is inadequacy,
hypersensitivity to criticism, and consequent social inhibition.
The major diagnostic distinction is between avoidant personality
disorder and social phobia, generalized type.
DEPENDENT PERSONALITY DISORDER

Individuals with dependent personality disorder are extremely
needy, relying on others for emotional support and decision
making.
Epidemiology
Lifetime prevalence is less than 1%.
Etiology
The etiology is unknown.
These people yearn to be cared for. Because of their extreme
dependence on others for emotional support and decision making,
they live in great and continual fear of separation from someone
they depend on, hence their submissive and clinging behaviors.
People with dependent personality disorder are similar to
individuals with borderline personality disorder in their desire to
avoid abandonment, but do not exhibit the impulsive behavior,
unstable affect, and poor self-image of the patient with borderline
personality.
OBSESSIVE–COMPULSIVE PERSONALITY DISORDER

These individuals are perfectionists who require a great deal of
order and control.
Epidemiology
The estimated prevalence is 2% to 8% in the general population.
Men are diagnosed with obsessive–compulsive personality disorder
twice as frequently as are women.
Etiology
The etiology is unknown, but there may be an association with
mood and anxiety disorders.
Individuals with obsessive–compulsive personality disorder are
perfectionists. They require order and control in every dimension
of their lives. Their attention to minutiae frequently impairs their
ability to finish what they start or to maintain sight of their goals.
They are cold and rigid in relationships and make frequent moral
judgments; devotion to work often replaces intimacy. They are
serious and plodding; even recreation becomes a sober task.
Obsessive–compulsive personality disorder can be differentiated
from obsessive–compulsive disorder depending on symptom
severity.
Management
Because personality may have temperamental components and is
developed over a lifetime of interacting with the environment,
personality disorders are generally resistant to treatment. In
general, psychotherapy is recommended for most personality
disorders. Psychodynamically based therapies are commonly
used, although they must be modified to each individual and each
disorder. Cognitive, behavioral, and family therapies are also
used to treat these disorders. Empirical studies validating the
efficacy of various therapies are generally lacking. Dialectical
behavioral therapy was developed specifically for the treatment
of borderline personality disorder and has been validated in
empirical studies. Group therapy incorporating various
psychotherapeutic modalities is also used.
Pharmacotherapy is widely used in personality disorders,
although no specific medication has been shown to treat any
specific disorder. Instead, medications are targeted at the various
associated symptoms of personality disorders. For example, mood
stabilizers may be used for mood instability and impulsiveness.
Benzodiazepines are commonly used for anxiety, although the
potential for abuse and dependence is too often overlooked. β-
Blockers are also used frequently. For depression, obsessive–
compulsive symptoms, and eating disturbances, selective
serotonin-reuptake inhibitors, and other antidepressants have been
successfully used. Psychotic or paranoid symptoms are commonly
treated with low-dose antipsychotics.
KEY POINTS
Personality disorders are categorized into three
symptom clusters.
Personality disorders consist of an enduring
pattern of experience and behavior.
The disorders can produce transient psychotic
symptoms during stress.
Treatment is with psychotherapy and medications
targeted at symptom relief.
Personality disorders are resistant to treatment.
Personality disorders may have genetic
associations with Axis 1 disorders.
CLINICAL VIGNETTES
VIGNETTE 1
A 24-year-old woman presents for a routine physical examination. You
are running late and have kept her waiting for 40 minutes alone in the
examination room. She is staring down at the floor when you arrive.
Apologizing, you begin to review her medical history. She begins to
cry and then suddenly gets angry when you ask whether the nurse
took her vitals. She says, “I was having such a nice conversation with
her, and then she just left and never returned.” You explain that there
are many other patients in your primary care office today and that she
had to go and see other patients. Sensing that she is still having
difficulties, you ask her what is going on in her life. She tells you that
her boyfriend of 2 months left her abruptly last month, and she has not
been able to stop crying. She describes her boyfriend as initially
“perfect” but later as “a disaster.” You query her about
neurovegetative symptoms (such as depressed mood, decreased
interests or pleasure, appetite change or weight loss or gain, sleep
disturbance, psychomotor agitation or retardation, fatigue or low
energy, worthlessness or guilt, impaired concentration or decision
making, thoughts of death or suicide), and she endorses some
symptoms but not enough to diagnose major depression. She clearly
brightens in response to your attention to her feelings, and you begin
examining her. She has numerous horizontal scars on both of her
forearms, some of which appear old and some more recent. You ask
how she got them, and her eyes avert to the floor again. “I did them,”
she states. “It makes the pain bearable.” You finish her examination
and refer her to a colleague for a psychiatric consultation.
1. From your recollections from your own psychiatric training in

medical school, you suspect she will be diagnosed with:
a. Narcissistic personality disorder
b. Major depression
c. Borderline personality disorder
d. Generalized anxiety disorder
e. Sexual masochism
2. The patient’s diagnosis is most strongly associated with:

a. Autism spectrum disorder
b. Abuse or severe neglect in childhood
c. Schizophrenia in one parent
d. Delusional disorder
VIGNETTE 2
A 45-year-old divorced man is referred to you from his company’s
employee assistance program because he is on probation at his job.
You are asked to evaluate him for the presence of a mental illness
that could be affecting his performance. He arrives for the
appointment 15 minutes late and looks annoyed with you. You
explain to him that his evaluation is confidential but that if there is
information that he would like shared with his employer to help
provide accommodations, you could provide such information. He
goes on to explain that he has been fired from or left several jobs in
the past because his coworkers failed to recognize his unique
talents. In each situation, he describes feeling as if he could have
led the organization better and that, in fact, he should be the boss.
He is surprised when you ask what qualities he has that he thinks
sets him apart. He blushes a bit, appearing humiliated, and then
snaps back at you, “What do you know about business leadership?
You’re a doctor.” You explain that you were curious about the
nature of his talents. He noticeably calms and then confesses that
he really does not have any talents and begins to cry. You listen
and talk some more and then complete your evaluation. He denies
neurovegetative signs of depression and exhibits no manic signs or
symptoms.
a. Schizoid personality disorder
b. Delusional disorder, grandiose subtype
d. Narcissistic personality disorder
e. Dependent personality disorder
ANSWERS
1. Answer C:
This patient shows many of the common features of borderline
personality disorder. She displays maladaptive coping patterns to
routine stress, exhibits emotional lability, perceives that she has been
abandoned by the nurse, and has a history of self-injurious behavior.
Although patients with this disorder have high rates of depression, she
does not meet criteria for an episode currently. Although she displays
some self-centeredness in her perception of the clinical staff
interaction, potentially consistent with narcissistic personality disorder,
the major issue is that she perceived being abandoned by the nurse.
She undoubtedly experiences anxiety related to her maladaptive
coping style, but she does not provide evidence of a persistent pattern
of worrying and physical symptoms that would characterize
generalized anxiety disorder. Finally, the self-injurious behavior of
cutting or scratching her forearms would not constitute masochism
because the patient does not report sexual gratification from the
behavior but rather a relief of emotional distress. Such self-injurious
behaviors are common features of borderline personality disorder.
2. Answer B:
The patient’s diagnosis is most strongly associated with abuse or
severe neglect in childhood. The risk for borderline personality
disorder is increased in individuals who have suffered from severe
neglect or from physical abuse in childhood. There is not strong
support for an association between childhood sexual abuse and
development of borderline personality disorder. Schizophrenia in one
parent increases the risk of psychosis and cluster A personality
disorders in the offspring but does not appear to increase the risk of
borderline personality disorder, a cluster B personality disorder. The
patient does not display evidence for delusional thinking, so delusional
disorder is not likely, although patients with borderline personality
disorder can have transient paranoia. Autism spectrum disorder is
characterized by deficits in two domains: impaired social
communication and interactions, and a repetitive or restricted
repertoire of activities and interests.
1. Answer D:
This man exhibits some common signs of narcissistic personality
disorder. His disregard of the time of the appointment, grandiosity
about his capabilities despite several failed jobs, and his sensitivity to
a mild suggestion that he might have a problem are behaviors seen
commonly with this disorder. Humiliation followed by anger is also a
common manifestation of narcissistic personality. The condition can
be quite disabling; as a consequence of the difficulties, such
individuals have tolerated the perceived slights omnipresent in nearly
every job setting. The aloofness and grandiosity are off-putting and
diminish empathy from others for one’s underlying pain. His interest in
interacting and pursuing work relationships makes schizoid personality
disorder unlikely. Although he is grandiose, his admission of
inadequacy is not consistent with a persistent, delusional grandiosity.
He is not self-destructive, impulsive, or afraid of abandonment, making
borderline personality disorder unlikely. He exhibits no features of
dependent personality disorder (extreme neediness and reliance on
others for emotional support and decision making).
Miscellaneous disorders do not refer to any official Diagnostic and
Statistical Manual of Mental Disorders, Fifth edition (DSM-5)
classification but rather to psychiatric diagnoses not covered
elsewhere in this book. Generally, these diagnoses are either less
common, less understood, or less frequently the focus of
psychiatric practice than the disorders previously covered.
Although many of these disorders are not uncommon, they seldom
come to psychiatric attention for a variety of reasons (e.g., they
may be treated by other medical specialists, patients may not
mention them, or they may not be detected adequately). Table 12-1
lists the categories of disorders discussed in this chapter.
TABLE 12-1. Miscellaneous Disorders

Somatic symptom and related disorders
Sexual dysfunctions
Paraphilic disorders
Gender dysphoria
Sleep–wake disorders
SOMATIC SYMPTOM AND RELATED

DISORDERS
Somatic symptom disorders are a new category in DSM-5. Unlike
many other psychiatric disorders, these are more likely to be
encountered in general medical settings, especially primary care.
The important disorders discussed here are somatic symptom
disorder, illness anxiety disorder, and conversion disorder (Table
12-2). All three are characterized as physical symptoms that are not
being willfully produced. In contrast, in factitious disorder,
symptoms are purposefully manufactured to gain medical attention.
Malingering is not a somatic symptom disorder, but occurs when
symptoms are purposefully manufactured to achieve some
secondary gain (money, drugs, avoidance of work or legal
consequences) and must be considered in the diagnosis of somatic
symptoms. Somatic symptoms often accompany other primary
psychiatric disorders, such as muscle tension in generalized anxiety
or parasthesias in panic attacks. If somatic symptoms are solely due
to another psychiatric condition, then the diagnosis of a somatic
symptom or related disorder cannot be made.
TABLE 12-2. Somatic Symptom and Related Disorders

Somatic symptom Individuals have one or more physical symptoms that
disorder cause disruptions in daily functioning due to
excessive worry or excessive energy devoted to
focusing on it.
Illness anxiety Individuals are preoccupied with the fear that they are
disorder seriously ill, leading to excessive medical utilization,
(hypochondriasis) tests, and interventions.
Conversion Individuals have complaints involving sensory (such
disorder as numbness) and voluntary motor (such as paralysis)
function that are not caused by neurologic
dysfunction.
Factitious Individuals purposefully manufacture medical illness
disorder or symptoms for the purpose of being cared and
playing the part of a patient. If there is evidence for
an external motivation (money, drugs, avoidance of
work), the diagnosis would be malingering.
SOMATIC SYMPTOM DISORDER

Individuals with somatic symptom disorder experience more
physical symptoms that cause persistent and excessive thoughts
about the symptom(s), high levels of anxiety about one’s health, or
excessive effort devoted to thinking about or dealing with the
symptom(s). Patients may experience multiple symptoms over a
period of time and they often last 6 months or more.
Patients can have no medical problems or they can have
comorbidly diagnosed medical problems that are the focus of
excessive worry or attention or that cause somatic symptoms that
are not physiologically likely given the organic medical problem.
Individuals are unlikely to be reassured by negative findings on a
medical workup or imaging, tend to be high utilizers of health care
resources, and tend to resist referral for mental health care. In
certain cultures, other psychiatric disorders may present as
primarily somatic symptoms, which may be more acceptable to a
patient to seek care for relative to emotional problems.
ILLNESS ANXIETY DISORDER (HYPOCHONDRIASIS)

Illness anxiety disorder is the DSM-5 equivalent of
hypochondriasis, which is the preoccupation with having a serious
illness. Affected individuals typically have very mild or no somatic
symptoms, but devote excessive worry to them nonetheless.
Individuals have a great deal of worry and will often compensate
by repeatedly seeking evaluation, reading about symptoms, or
attempting treatments. A subset of patients will avoid physicians or
hospitals because of fear of acquiring or uncovering a serious
illness.
Unlike the other somatic symptom disorders, illness anxiety
disorder occurs roughly equally in men and women. Care should be
taken to distinguish normal stress and anxiety about medical illness
from pathologic worry. Obsessive–compulsive disorder should also
be on the differential diagnosis, wherein the individual has
intrusive worry about acquiring an illness rather than excessive
worry that they already have an illness.
CONVERSION DISORDER (FUNCTIONAL NEUROLOGIC

SYMPTOM DISORDER)
Patients with conversion disorder display one or more motor,
perceptual, or cognitive symptom with clinical findings that do not
support an organic etiology for those symptoms. Patients are not
consciously producing these symptoms, although through
examination techniques a clinician may be able to separate true
neurologic weakness or sensory deficits from those related to a
conversion disorder. Common symptoms are weakness, complete
paralysis (often not following anatomic boundaries), abnormal
movements, speech changes, sensory loss, seizures, or dysphagia.
Common comorbid findings in patients with conversion
disorder are dissociation, derealization, and depersonalization.
Patients may display a lack of concern for the symptoms (la belle
indifference), different from the excessive worry of somatic
symptom disorder. If there is concern that the symptoms are being
consciously produced, the diagnosis would be either factitious
disorder or malingering. There is a strong association with early
life trauma. Often, patients can have resolution or dramatic
improvement in their symptoms with psychoeducation, individual
psychotherapy, and management of any psychiatric comorbidities.
FACTITIOUS DISORDER
Patients with factitious disorder purposefully produce symptoms
either on themselves (factitious disorder imposed on self) or others
(factitious disorder imposed on another). Individuals may feign
subjective symptoms, physiologic signs, may cause overt injury or
infection, may tamper with medical equipment, may
inappropriately administer medications, or falsify their medical
history. Importantly, there is no evidence for an external reward as
a result of having the symptoms. Rather, patients are motivated by
their need to be in the sick or dependent role.
In factitious disorder imposed on another, the caregivers are
producing symptoms in their dependents (children, elders, and
animals). This behavior cannot be due solely to lying to avoid some
legal or other consequence or in pursuit of some monetary or other
reward. If individuals are feigning symptoms for the purpose of
gaining an external reward (or secondary gain), the diagnosis
would be malingering.
The diagnosis of factitious disorder is very difficult to make in
inpatient settings and even more so in ambulatory settings. Often,
extensive evaluation or treatment has taken place by the time the
diagnosis is made. Even though individuals are producing
symptoms consciously, they are still at risk of the medical
consequences of their actions, including infection, severe injury, or
death. They may further complicate their care by engaging in
behaviors that interfere with treatment. Oftentimes a
multidisciplinary approach with clear communication and
environmental safeguards is required to effectively manage
individuals with factitious disorder.
SEXUAL DYSFUNCTIONS
Sexual dysfunction in DSM-5 encompasses a wide range of
disorders that affect individuals at different stages of the sexual
response cycle. The specific disorders may be described as lifelong
or acquired, generalized (for disorders that are present in all
situations and with all partners), or situational (if they are limited to
specific types of stimulation, situation, or partner). Diagnoses can
further be described by the degree of distress caused to the patient
(mild, moderate, or severe). Diagnoses of sexual dysfunction
should not be made if the cause of the sexual problems is related
only to lack of appropriate stimulation (uneducated or
inexperienced partners), religious or cultural prohibitions, normal
processes of aging, relationship factors (abuse, poor
communication), medical illnesses (neuropathy, vascular disease),
or psychiatric illness (depression, anxiety, posttraumatic stress
disorder, among others). The specific sexual dysfunctions are
summarized in Table 12-3.
TABLE 12-3. Sexual Dysfunctions

Delayed ejaculation Delay, infrequency, or absence of ejaculation in
>75% sexual encounters for greater than 6
months
Only 75% of men describe achieving orgasm
during every sexual encounter.
Erectile disorder In >75% of sexual encounters, decreased ability
to achieve or maintain an erection, or marked
decrease in erectile rigidity for greater than 6
months
There is a strong association with age, with only
2% of men younger than 40 but >40% of men
older than 60 experiencing erectile problems.
Female Orgasmic Delay, infrequency, absence, or decreased
Disorder intensity of orgasms in >75% of sexual
encounters lasting for greater than approximately
6 months
Approximately 10% of women will report never
having achieved orgasm during their lifetime.
Female sexual For greater than 6 months, the experience of
interest/arousal reduced or absent sexual activity,
disorder thoughts/fantasies, initiation of sexual activity,
pleasure, response to genital or nongenital sexual
stimulation, or response to verbal, visual, or
auditory sexual cues (need at least three).
Genito-pelvic Recurrent problems with vaginal penetration,
pain/penetration vulvovaginal or pelvic pain during intercourse,
disorder anticipatory fear or anxiety when thinking about
penetration, or tension in the pelvic floor muscles
during attempted vaginal penetration (need at
least one), lasting longer than 6 months.
Male hypoactive Reduced or absent sexual desire for sexual
sexual desire disorder activity or fantasies about sexual activity lasting
greater than 6 months
For both male and female hypoactive sexual
desire, the criteria are not met if the lack of
desire is only relative to a partner’s increased
level of desire (the “desire discrepancy”).
Premature (Early) Ejaculation within one minute of initiation of
Ejaculation intercourse
20%–30% of men report concerns about early
ejaculation, although only 1%–3% of men meet
DSM-5 criteria for the disorder.
Substance/medication- Significant and distressing sexual dysfunction
induced sexual related to intoxication or withdrawal or a
dysfunction substance. The most common substances of
abuse associated with sexual dysfunction are
Alcohol
Opiates
Sedative-hypnotics (benzodiazepines)
Amphetamines
Cocaine
Tobacco
Other medications associated with sexual
dysfunction include SSRIs and TCAs,
antipsychotics, antihypertensives, and hormonal
contraceptives, among others.
SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic antidepressants.
PARAPHILIC DISORDERS
Paraphilic disorders include sexual disorders related to culturally
unusual sexual activity over a period of at least 6 months that do
not include sexual interest or arousal with phenotypically normal,
physically mature, and consenting partners (Table 12-4). A key
criterion for the diagnosis of paraphilic disorders (as in all
psychiatric disorders) is that the disorder must cause an individual
to experience significant distress or impairment in social or
occupational functioning. In other words, an individual with
unusual sexual practices who does not suffer significant distress or
impairment would not be diagnosed with a psychiatric illness. A
crucial difference exists among a paraphilia and a paraphilic
disorder; the former is an atypical sexual behavior, whereas the
latter is the disorder stemming from that behavior.
TABLE 12-4. Paraphilic Disorders

Exhibitionistic Sexual excitement is derived from exposing one’s
disorder genitals to a nonconsenting stranger.
Fetishistic Nonliving objects and highly specific nongenital body
disorder part(s) are the focus of intense sexual arousal in fantasy
or behavior.
Frotteuristic Sexual excitement is derived by rubbing one’s genitals
disorder against or by sexually touching a nonconsenting stranger.
Pedophilic Sexual excitement is derived from fantasy or behavior
disorder involving sex with prepubescent children.
Sexual Sexual excitement is derived from fantasy or behavior
masochism involving being the recipient of humiliation, bondage, or
disorder pain.
Sexual sadism Sexual excitement is derived from fantasy or behavior
disorder involving inflicting suffering/humiliation on another
individual.
Transvestic Sexual excitement is derived from fantasy or behavior
disorder involving dressing as the opposite sex.
Voyeuristic Sexual excitement is derived from fantasy or behavior
disorder involving the observation of unsuspecting individuals
undressing, naked, or having sex.
GENDER DYSPHORIA
Previously known as gender identity disorder, gender dysphoria
remains a controversial diagnosis in psychiatry. Individuals with
this disorder experience distress and interpersonal impairment as a
result of their identification with a different gender than their birth.
Criteria for the diagnosis in children require a strong desire to be of
the other gender, strong preference for playmates, toys, and
clothing typical of the other gender, and dislike of one’s own
anatomy and a desire to manifest secondary sex characteristics of
the other gender. In adolescents and adults, the criteria require
incongruence between one’s gender identity and their phenotypic
gender, strong desire to change or remove their secondary sex
characteristics, and strong desire to be treated as another gender.
The diagnosis may or may not be associated with a disorder of
sexual development such as androgen insensitivity syndrome.
Often, these individuals will pursue hormonal therapy or gender-
reassignment surgery. Importantly, the diagnosis of gender
dysphoria can only be made if the symptoms described are causing
significant distress or impairment.
SLEEP–WAKE DISORDERS
NORMAL SLEEP ARCHITECTURE AND

POLYSOMNOGRAPHY
Sleep and related parameters are objectively assessed through the
use of polysomnography (Fig. 12-1). Polysomnography records the
electroencephalogram (EEG) using scalp electrodes, and the
measured EEG wave forms are used to identify specific sleep
stages (Table 12-5 and Fig. 12-2). Polysomnography also records
eye movements (electrooculogram), muscle tone and activity via
the electromyogram, electrocardiogram activity, respirations,
respiratory effort, pulse oximetry, and leg movements.
FIGURE 12-1. A patient during polysomnography. Polysomnography
records electroencephalography (EEG) using scalp electrodes, and
the measured EEG wave forms are used to identify specific sleep
stages (Table 12-5 and Fig. 12-2). Polysomnography also records eye
movements (electrooculogram), muscle tone and activity via the
electromyogram, electrocardiogram activity, respirations, respiratory
effort, pulse oximetry, and leg movements. (From Boyd MA.
Psychiatric Nursing: Contemporary Practice, 6th ed. Philadelphia, PA:
Wolters Kluwer, 2017.)
TABLE 12-5. Sleep Stages
NREM (75% of total sleep time)
Stage 0 Awake
Stage 1 (5% of Very lighta sleep, transition from wakefulness to
total sleep time) sleep. Drowsy.
Stage 2 (45% of Medium depth of sleep, occupies about half the
total sleep time) night in adults.
Serves as a transition stage between REM and delta
sleep. EEG demonstrates sleep spindles and K-
complexes.
Delta (slow-wave
sleep) comprises
stages 3 and 4
Stage 3 (12% of Consists of a moderate amount of delta wave
total sleep time) activity; deeper sleep than stage 2.
Stage 4 (13% of Increased delta wave activity over stage 3. Very
total sleep time) deep stage of sleep.
REM (25% of total Dream sleep. EEG is active, mimicking that of the
sleep time) waking stage. Depth of sleep is greater than stage 2
but probably less than delta.
aDepth of sleep as used here is not a precise term but generally refers to ease of arousability (i.e.,
how hard would it be to awaken an individual from a particular stage); however, the ease of
arousability is caused in part by the type of stimulus used (e.g., noise vs. touch).
EEG, electroencephalogram; NREM, non–rapid eye movement; REM, rapid eye movement.
FIGURE 12-2. Left: Electroencephalogram activity during the awake
state and during stages 1–4. The electroencephalography pattern in
rapid eye movement (REM) sleep resembles that of the awake state.
Right: Sleep histogram plotting the duration and pattern of sleep
stages during the night. Notice that stages 3 and 4 are more
prominent early in the night, but that REM sleep is more prominent
later in the sleep event. (From Porth CM. Pathophysiology: Concepts
of Altered Health States, 7th ed. Philadelphia, PA: Lippincott Williams
& Wilkins, 2005.)
Sleep stages are summarized in Table 12-5. Figure 12-3

summarizes the neural structures that are implicated in sleep/wake
regulation. Neural regions mediating sleep–wake cycles interact
strongly with brain regions mediating circadian rhythms. The
suprachiasmatic nucleus (Fig. 12-4) mediates circadian rhythms
and influences sleep, in part through regulation of melatonin, a
hormone that increases in darkness and that is sleep-inducing.
FIGURE 12-3. Neural systems implicated in sleep/wake regulation.
The acetylcholine, hypocretin, histamine, serotonin, and
norepinephrine neurons promote and maintain wakefulness through
projections to the thalamus and neocortex. Adenosine has a role in
sleep induction and inhibits these systems. (From Bear MF, Connors
BW, Paradiso MA. Neuroscience, 4th ed. Philadelphia, PA: Wolters
Kluwer, 2015.)
FIGURE 12-4. The suprachiasmatic nucleus (SCN) entrains multiple
circadian rhythms. The SCN receives information on light and dark
input from the retina. Upper panels: Sagittal view of the brain with the
SCN in green. Lower panel: Coronal view of the brain showing
relationship of SCN to third ventricle and optic chiasm. (From Bear
MF, Connors BW, Paradiso MA. Neuroscience, 4th ed. Philadelphia,
PA: Wolters Kluwer, 2015.)
SLEEP DISORDERS
The DSM-5 substantially revised the classification of sleep
disorders, eliminating the previous categories of primary and
secondary disorders, among other changes. The classification of
sleep disorders is outlined in Table 12-6.
TABLE 12.6. Sleep–Wake Disorders

Insomnia disorder
Hypersomnolence disorder
Narcolepsy
Breathing-related sleep disorders
Obstructive sleep apnea hypopnea
Central sleep apnea
Sleep-related hypoventilation
Circadian rhythm sleep–wake disorders
Parasomnia
Non–rapid eye movement sleep arousal disorders
Nightmare disorder
Rapid eye movement sleep disorder
Restless legs syndrome
Substance/medication-induced sleep disorder
Insomnia Disorder
Insomnia disorder can now be diagnosed in the presence of
comorbid conditions such as depression and anxiety unless they
seem to fully account for the condition. In insomnia disorder, the
primary symptom is difficulty sleeping, either in initiating sleep,
maintaining sleep, or with early morning awakenings. The
insomnia must be sufficiently severe as to cause distress or
impairment and cannot be due to substances. The difficulty
sleeping should occur at least three nights per week and persist for
at least 3 months before insomnia disorder is diagnosed.
Hypersomnolence Disorder
The key feature of hypersomnolence disorder is excessive daytime
sleepiness despite nighttime sleep of at least 7 hours. Symptoms
include at least one of the following: (1) falling asleep during the
day; (2) sleeping 9 hours or more in a single episode without
feeling refreshed; (3) not waking up fully after awakening. The
excess sleepiness should occur at least 3 days per week for at least
3 months for a diagnosis of hypersomnolence disorder.
Narcolepsy
Narcolepsy is characterized by excessive daytime sleepiness as
manifested by the need to take naps, falling asleep, and having a
strong urge to sleep. Symptoms must occur at least three times per
day and persist for 3 months. In addition to these symptoms, a
person must have cataplexy, hypocretin deficiency, or sleep-onset
rapid eye movement (REM) episodes as measured by
polysomnography. In recent-onset narcolepsy (less than 6 months)
and in children, cataplexy can spontaneously manifest as
grimacing, mouth opening with tongue protrusion, or loss of
muscle tone (hypotonia). In adults with more chronic illness,
cataplexy is caused by laughter or joking (or any other emotional
trigger) and is manifest as sudden loss of whole body muscle tone
(often with falling to floor if standing) without loss of
consciousness. Hypocretin deficiency should be measured in
cerebrospinal fluid. Sleep-onset REM periods are diagnosed when
REM onset latency is ≤15 minutes as measured using nocturnal
polysomnography or during the multiple sleep latency test (a test
during which a person is put to bed multiple times during the day
while undergoing polysomnography) an average sleep latency of
≤8 minutes or at least two sleep-onset REM episodes. There are
multiple specifiers for narcolepsy diagnosis: (1) narcolepsy without
cataplexy but with hypocretin deficiency; (2) narcolepsy with
cataplexy but without hypocretin deficiency; (3) autosomal
dominant cerebellar ataxia, deafness, and narcolepsy; (4) autosomal
dominant narcolepsy, obesity, and type 2 diabetes; and (5)
narcolepsy due to another medical condition that causes loss of
hypocretin neurons.
BREATHING-RELATED SLEEP DISORDERS

There are three categories of breathing-related sleep disorders: (1)
obstructive sleep apnea hypopnea; (2) central sleep apnea; and (3)
sleep-related hypoventilation.
Obstructive Sleep Apnea Hypopnea

Obstructive sleep apnea hypopnea is a condition characterized by
repeated upper airway obstruction during sleep that leads to
reduced oxygenation and sleep fragmentation. Apnea is defined
when there is no airflow for ≥10 seconds. Hypopnea is a reduction
in airflow. Daytime sleepiness and snoring are strong clinical clues
to the condition. This condition is diagnosed by polysomnography
either by a combination of breathing measures and symptoms (at
least five obstructive apneas or hypopneas per hour plus symptoms
such as breathing pauses, snorting or gasping during sleep, or
excessive daytime sleepiness and fatigue) or irrespective of clinical
symptoms if the apnea/hypopnea count is greater than 15 episodes
per hour.
Central Sleep Apnea

Central sleep apnea occurs when breathing stops in the absence of
an upper airway obstruction. Central sleep apnea is diagnosed via
polysomnography when there are five or more central apneas per
hour of sleep. There are three subtypes of central sleep apnea: (1)
idiopathic central sleep apnea is diagnosed if there is
apnea/hypopnea but no evidence of airway obstruction; (2) Cheyne
stokes breathing type; and (3) central sleep apnea due to opioid use.
Sleep-Related Hypoventilation
Sleep-related hypoventilation is diagnosed either when there is
shallow respiration with elevated carbon dioxide levels or when
there is oxygen desaturation in the absence of apneic events.
CIRCADIAN RHYTHM SLEEP–WAKE DISORDERS

Circadian sleep disorders occur when a person’s preferred sleep
schedule does not align with the endogenous/biologic circadian
rhythm. Results can be insomnia or excess sleepiness depending on
the time of day. There are multiple subtypes of circadian disorders.
Most prominently, delayed sleep phase type, which is common in
adolescents and young adults, is difficulty falling asleep at an early
time that is desired or necessary. Advanced sleep phase type, which
is more common in the elderly, is a pattern of falling asleep earlier
than desired or necessary.
PARASOMNIAS
Parasomnias are conditions in which abnormal behaviors occur
during sleep or sleep/wake transitions. They include non–rapid eye
movement (NREM) sleep arousal disorders; nightmare disorder;
and REM sleep disorder.
Non–Rapid Eye Movement Sleep Arousal Disorders

NREM sleep arousal disorders include sleepwalking or sleep
terrors. In sleepwalking, feeding behavior or sexual behavior can
occur. In sleep terrors, individuals may scream out and appear to be
very frightened, but are usually unresponsive to others. Individuals
with sleepwalking or sleep terrors do not remember the events.
Nightmare Disorder
In nightmare disorder, an individual has recurrent nightmares that
are unpleasant or scary and that are well remembered.
Rapid Eye Movement Sleep Disorder

In REM sleep disorder, individuals are thought to be acting out
aspects of their dreams through vocalizing and movement. The
activities occur during REM sleep.
Restless Legs Syndrome

In restless legs syndrome, individuals develop unpleasant sensation
in their legs that leads to a strong desire to move their legs to
relieve the unpleasant feeling. This condition occurs only at night
or worsens at night and is also worse when sitting still.
SUBSTANCE/MEDICATION-INDUCED SLEEP DISORDER

Substance/medication-induced sleep disorder is diagnosed when
intoxication or withdrawal from medications or illicit drugs lead to
sleep disturbance.
KEY POINTS
Somatic symptom disorder is a type of somatic
symptom and related disorder.
The symptoms of somatic symptom disorder are
subconscious in origin.
Treatment of somatic symptom disorder includes
cognitive-behavioral therapy, antidepressants, and
single-physician structured treatment.
Paraphilias are sexual behaviors or interests that
are considered culturally unusual.
Factitious disorder is characterized by the willful
production of symptoms of illness to assume the
sick role.
CLINICAL VIGNETTES
VIGNETTE 1
A 56-year-old man with a history of mild hypertension and obesity
presents to his primary care physician for treatment of daytime
sleepiness and fatigue. The patient reports that he has been
becoming progressively more fatigued over the past 2 to 3 years and
has gained around 25 lb because he has no energy to move around.
He has been increasing his caffeine intake to the point that he feels
jittery and nervous, but he is still tired, dozes off quite frequently
during the day, and has fairly frequent headaches. After obtaining a
detailed medical and psychiatric history, you ask the patient about his
time in bed at night. He states that he sleeps alone after his last bed
partner complained that he snored very loudly and sounded like he
was choking all night.
1. After completing the interview, you make which of the following

provisional diagnoses for the patient’s complaints:
a. Hypothyroidism
b. Hyperthyroidism
c. Narcolepsy
d. Major depression
e. Breathing-related sleep disorder
2. The patient undergoes an overnight polysomnographic evaluation

to evaluate his sleep concerns. The finding that is consistent with
obstructive sleep apnea hypopnea is:
a. Rapid eye movement (REM) onset latency is ≤15 minutes
b. REM onset latency is >90 minutes
c. The patient remains in bed for over 9 hours
d. Over 15 episodes per hour of no airflow for ≥10 seconds
e. Frequent muscle contractions that interrupt sleep as measured
by tibial electromyogram (EMG)
VIGNETTE 2
A 27-year-old man complains of excess sleepiness during the day and
having intense dreams at times when he thinks he is still awake. He
notes that he sometimes has an irresistible urge to sleep and has
fallen asleep on multiple occasions even while driving. He feels
refreshed after a daytime nap. Upon questioning, he reports that he
sometimes has “drop” attacks characterized by sudden weakness in
his whole body, especially when laughing. He remains alert during the
drop attacks but does fall to the floor.
1. The most appropriate next step to further evaluate the patient is:
a. Referral to psychiatry for treatment of conversion disorder
b. Nocturnal polysomnography to evaluate for breathing-related
sleep disorder
c. Daytime multiple sleep latency test to evaluate for narcolepsy
d. Thyroid function studies
2. An appropriate treatment intervention is:

a. Continuous positive airway pressure at night to improve
abnormal breathing during sleep
b. Administration of zolpidem (Ambien) at bedtime to improve
nighttime sleep
c. Valproic acid to treat seizure activity
d. Modafinil to improve daytime alertness
e. Olanzapine to improve daytime alertness
VIGNETTE 3
A 38-year-old female patient presents to the emergency room with
sudden-onset lower extremity weakness. She described that this had
happened several times in the past but “it always got better on its
own.” This episode started the night prior, and when it did not resolve
by the morning she called an ambulance to bring her to the
emergency room. Her initial physical exam was significant for one-fifth
strength in her leg extensors, flexors, and at her ankles. The
remainder of her exam is essentially normal. Her vital signs have been
stable and in the normal range. Her complete blood counts and
complete metabolic panel are within normal limits. The patient has a
history of hypertension and hyperlipidemia and is nonadherent to her
prescribed medications. She denied a history of depression, anxiety,
and other psychiatric symptoms other than intermittent insomnia. She
smokes one pack of cigarettes daily but denied use of any other
substances of abuse. The emergency room physicians are trying to
determine the best plan of care for this patient.
1. After obtaining a normal computed tomography (CT) of the head,

neck, and spine, the patient states “the test must have missed
something” and becomes more distressed. Gathering more
history, you learn that the patient’s husband could not be at the
hospital with her because he was working extra shifts in recent
months. Given this information, which of the following statements
is most accurate?
a. The patient has conversion disorder because there is no
evidence for a structural problem that explains her symptoms.
b. The patient is most likely malingering because she is so
insistent that the test has missed her diagnosis.
c. The physicians cannot diagnose malingering or factitious
disorder on the basis of the available information.
d. The patient most likely has factitious disorder because her
needs are not being met at home.
e. The patient cannot have conversion disorder because she is
distressed by the negative test results.
2. After additional testing, the emergency room physicians

determine that the patient most likely has a functional neurologic
deficit and ask for a psychiatric consultation. Which of the
following would be the strongest evidence for this patient’s
presentation being a functional neurologic deficit?
a. Bilateral but asymmetric weakness of her quadriceps
b. Unilateral sensory deficit in a band that runs down the lateral
leg to the top of the foot
c. Symmetrical arthralgia of the knees and ankles that is worse
with movement
d. Weakness of contralateral hip flexion when attempting hip
extension
e. Toe extension with pressure applied to the sole of the foot in a
heel-to-toe direction
3. During the interview, the psychiatrist explores the patient’s social

and developmental history. Which of the following is least likely to
be present in a patient with conversion disorder?
a. Early childhood neglect
b. Recent loss of employment
c. Failing out of a nursing assistant training program
d. A pending worker’s compensation claim
e. Being the sole caregiver for two young children
VIGNETTE 4
A 35-year-old Caucasian male with no significant past medical history
presents for his initial primary care visit. During your assessment, he
disclosed that he has been more irritable lately. He reports feeling
stressed out after moving to a new town 3 months ago. He is a
successful lawyer and lives with his wife and 2-year-old son. His wife
noted that he was very excited and happy about moving to a new city
a few months ago; however, he now feels overwhelmed with his new
job, financial responsibilities, and not having family or friends around.
He is tired and jittery throughout, and he markedly worried about his
family’s future. His performance at work is fair; however, he has been
spending more time by himself. He denies sleep disturbances,
anhedonia, or appetite changes. He denies suicidal ideation or other
physical complaints.
1. What is the patient’s most likely diagnosis?

a. Major depressive disorder
b. Panic disorder with agoraphobia
c. Adjustment disorder
d. Acute stress disorder
e. Posttraumatic stress disorder
2. What is the most appropriate next step?

a. Start fluoxetine and cognitive-behavioral therapy
b. Refer for electroconvulsive therapy (ECT)
c. Start venlafaxine
d. Supportive psychotherapy
e. Referral to psychiatry for further management
3. Which of the following symptoms would lead you to consider

starting an antidepressant on this patient?
a. Insomnia
b. Tearfulness
c. Mood swings
d. Nervousness
e. Passive suicidal ideation
4. How long would most likely take for his symptoms to go away
after the stressors resolve?
a. Less than 6 months
b. A month
c. 6 to 12 months
d. Longer than a year
e. They will likely get worse.
5. What laboratory tests would you order for this patient in the
context of his current symptoms?
a. Vitamin B12 and thyroid-stimulating hormone
b. Comprehensive metabolic panel
c. Complete blood count
d. None
ANSWERS
1. Answer E:
There are three categories of breathing-related sleep disorders: (1)
obstructive sleep apnea hypopnea; (2) central sleep apnea; and (3)
sleep-related hypoventilation. Breathing-related sleep disorders are
conditions characterized by disordered breathing during sleep that
results in frequent awakening and fragmentation of nighttime sleep
with resultant daytime sleepiness. The patient’s syndrome complex is
consistent with obstructive sleep apnea hypopnea, a category of
breathing-related sleep dysfunction consisting of recurrent episodes of
apnea while sleeping. The presence of loud snoring and choking or
gasping during sleep is a cardinal sign of this condition. Patients often
report fatigue and headache.
2. Answer D:
The finding that is consistent with obstructive sleep apnea hypopnea
is over 15 episodes per hour of no airflow for ≥10 seconds.
Obstructive sleep apnea hypopnea is definitely diagnosed in the face
of recurrent periods of apnea or hypopnea. These periods of reduced
breathing are associated with frequent awakenings and lead to
excessive daytime somnolence, among other consequences. REM
onset latency ≤15 minutes in someone who is not sleep deprived is
suggestive of narcolepsy, especially when there are multiple episodes
during the multiple sleep latency test. REM onset latency is normally
90 minutes and shorter onset latency (if narcolepsy is ruled out) can
be suggestive of major depression whereas longer latency is
potentially suggestive of anxiety if the patient reports symptoms
consistent with these conditions. Remaining in bed for 9 hours could
be healthy or could suggest a problem, depending on the person’s
intent in remaining in bed. Frequent muscle contractions (periodic leg
movements) that interrupt sleep as measured by tibial EMG can be
suggestive of restless legs syndrome.
1. Answer C:
The clinical history is most consistent with a diagnosis of narcolepsy, a
condition characterized by daytime sleep attacks, cataplexy (sudden,
reversible, bilateral loss of skeletal muscle tone), sleep paralysis
(temporary paralysis upon awakening from sleep), and REM sleep
intrusions (experienced as sudden vivid dreams that may intrude into
the waking state). If experienced at sleep onset, the REM intrusions
are called hypnagogic hallucinations. If experienced at awakening, the
REM intrusions are called hypnopompic hallucinations. The diagnosis
of narcolepsy requires in part the presence of sleep-onset REM
periods. Criteria require either REM onset latency ≤15 minutes as
measured using nocturnal polysomnography or an average sleep
latency of ≤8 minutes or at least two sleep-onset REM episodes during
the multiple sleep latency test (a test during which a person is put to
bed multiple times during the day while undergoing
polysomnography). Additional diagnostic criteria include hypocretin
deficiency as measured via cerebrospinal fluid.
2. Answer D:
Modafinil to improve daytime alertness is an appropriate treatment
intervention. The clinical history is most consistent with a diagnosis of
narcolepsy, a condition characterized by daytime sleep attacks,
cataplexy (sudden, reversible, bilateral loss of skeletal muscle tone),
sleep paralysis (temporary paralysis on awakening from sleep), and
REM sleep intrusions (experienced as sudden vivid dreams that may
intrude into the waking state). If experienced at sleep onset, the REM
intrusions are called hypnagogic hallucinations. If experienced at
awakening, the REM intrusions are called hypnopompic
hallucinations. Modafinil is an approved treatment for narcolepsy and
enhances daytime alertness. Continuous positive airway pressure at
night to improve abnormal breathing is an appropriate treatment for
breathing-related sleep disorder. Administration of zolpidem at
bedtime is an appropriate short-term treatment for insomnia. Valproic
acid is used in the treatment of bipolar disorder and seizure disorder
but not for narcolepsy. The patient’s drop attacks with retained
consciousness do not suggest a diagnosis of seizure disorder.
Sleepiness in the absence of mood symptoms does not suggest a
diagnosis of bipolar disorder. Olanzapine, an atypical antipsychotic
medication, is quite sedating and would likely exacerbate daytime
sleepiness.
1. Answer C:
This question requires knowledge of the differences between
conversion disorder, factitious disorder, and malingering. The lack of a
clear structural lesion on the initial CT scan is supporting evidence for
a somatoform or related disorder but does not help to distinguish
between the different diagnoses and does not rule out other
neurologic problems that a CT scan would miss. A patient being upset
about negative test results is nonspecific. While a classical finding of
conversion disorder is a lack of distress over the symptoms being
experienced (la belle indifference), this is not universally present and
the patient experiencing distress does not rule out conversion
disorder. Understanding potential motivations behind feigned
symptoms is important for distinguishing between factitious disorder,
in which the symptoms serve to support a primary need to be cared
for, and malingering, in which symptoms are intended to gain some
secondary financial, legal, or other benefit. There is not enough
information to distinguish between these two. Given the continued
uncertainty, the only remaining choice is to avoid making a definitive
diagnosis.
2. Answer D:
Testing for functional neurologic signs requires knowledge of normal
physiology and the deficits that are expected from neurologic insults.
Quadriceps weakness can be a result of lumbar spine or femoral
nerve pathology which may often be asymmetrical. The distribution of
the sensory deficit in answer choice B can be the result of an L5
radiculopathy. Patients with conversion disorder hemi-anesthesia may
describe loss of sensation that does not follow normal dermatomal
distribution such as a sensory deficit in a glove or stocking pattern.
Answer choice C seems to be describing fairly common symptoms of
osteoarthritis, which may be present despite the patient’s young age.
Answer choice E describes the Babinski maneuver, in which a hard,
firm pressure is applied along the sole of the foot from heel to toe and
the reaction of the toes is observed. Babies and patients with upper
motor neuron disease may have an extensor response (upgoing toes),
while normal adults should have toe flexion. Answer choice D
describes a positive Hoover sign, one of the common tests for
conversion weakness. Normally, lifting one leg while lying supine
reflexively causes contraction of the contralateral leg for stabilization.
The Hoover sign is positive when the patient has no contraction of the
contralateral leg while attempting to flex at the hip. This is suggestive
of a functional neurologic deficit.
3. Answer D:
Risk factors for conversion disorder include female gender, a history
of trauma, recent stressors, having other psychiatric illnesses such as
depression and anxiety, having organic neurologic disorders, and
having a family history of conversion disorder. Of the answer choices
above, all but answer D describe trauma and stress, which are all
consistent with a diagnosis of conversion disorder. Conversion
disorder is distinguished from factious disorder and malingering by the
fact that patients are unconsciously producing symptoms and the
potential benefits of producing these symptoms are often unclear. If
there is evidence that the patient’s production of symptoms is
motivated by external gains, such as in answer choice D, there would
be some suspicion for a diagnosis of malingering. Importantly, patients
with conversion disorder often do receive monetary, social, and other
benefits resulting from their symptoms, so the fact that a potential gain
is identified does not definitively rule out conversion disorder.
1. Answer C:
Adjustment disorder is characterized by emotional or behavioral
disturbances in response to a recent identifiable stressor(s). These
symptoms are out of proportion to the severity of the stressor, and
cultural context. Adjustment disorder symptoms negatively impact
social, occupational, and other important aspects in life. These
symptoms or behaviors begin within 3 months of onset of a stressor
and tend to last no longer than 6 months after the stressor has
ceased. In this case, the patient has experienced irritability, tiredness,
and anxiety related to moving to a new town, which are consistent with
adjustment disorder. He does not meet criteria for major depressive
disorder as he has not experienced anhedonia, appetite changes, or
sleep disturbances. The case does not describe any signs or
symptoms consistent with posttraumatic stress disorder, acute stress
disorder, or panic disorder.
2. Answer D:
Adjustment disorder responds well to nonpharmacologic interventions,
particularly supportive psychotherapy. This disorder usually resolves
spontaneously within 6 months after the stressor has ceased;
therefore, psychotherapy is the first-line treatment. Although,
supportive psychotherapy is the most common approach for
adjustment disorder, other therapy treatment modalities such as
cognitive-behavioral therapy are also indicated. Pharmacotherapy is
not usually indicated; however, antidepressants or anxiolytic
medications may be considered in certain cases. ECT is not indicated
for patients with adjustment disorder; however, ECT should be
considered for treatment-resistant depression, among other
conditions. Referral to psychiatry is not required as adjustment
disorder can be easily treated by a primary care provider.
3. Answer E:
It is important to differentiate adjustment disorder from major
depressive disorder because they have clinical features in common,
and the treatment options for each of them may differ. The severity of
the symptoms and clinical course are key to differentiate these
conditions. As mentioned above, adjustment disorder will most likely
resolve within 6 months after the stressor and its consequences have
ceased, whereas symptoms of depression will likely remain beyond
that. The presence of suicidal ideation and neurovegetative symptoms
(appetite, weight changes, and sleep disturbances) along with severe
clinical features are consistent with major depressive disorder rather
than adjustment disorder. Short temper, tearfulness, mood swings,
and nervousness are common symptoms of adjustment disorder.
4. Answer A:
Symptoms of adjustment disorder begin within 3 months of onset of a
stressor and last no longer than 6 months after the stressor and its
consequences have ceased. If behavioral and emotional symptoms
persist beyond 6 months, major depressive disorder should be
strongly considered in the differential diagnosis. The other alternatives
are not consistent with the usual presentation and timeline of
adjustment disorder.
5. Answer D:
Adjustment disorder is a clinical diagnosis, as such only history and
physical findings are necessary. It is important to mention that vitamin
B12 and thyroid-stimulating hormone should be ordered on patients
with a new diagnosis of major depressive disorder to exclude potential
medical illnesses that may present as depression. In this particular
case, no laboratory test should be ordered because the patient does
not meet criteria for major depressive disorder or have signs of other
medical problem.
SUICIDE ATTEMPTS
NEURAL BASIS
Emerging evidence has begun to reveal neurobiologic contributors
to suicidal behavior. There is considerable evidence that altered
central nervous system serotonin is associated with increased
suicide risk. Altered serotonin markers include reduced
cerebrospinal fluid serotonin metabolites, reduced brain serotonin
concentration, and increases in numbers of brainstem serotonin
neurons, the serotonin transporter, and serotonin 1A receptors.
Alterations in the tryptophan hydroxylase gene, a key enzyme in
serotonin synthesis, have been associated with suicide risk. Other
differences found in association with suicide attempts include
reductions in norepinephrine neurons of the locus coeruleus,
volume loss in some prefrontal cortical regions, and alterations in
the hypothalamic–pituitary–adrenal axis. Increased peripheral
inflammation is also emerging as a risk factor for suicide. Genetic
influences have not been thoroughly explored, but the concordance
rate for suicide in monozygotic twins is nearly 10-fold that of
dizygotic twins and about 50% of the risk for suicide is thought to
be inherited.
EPIDEMIOLOGY
Suicide was the 10th leading cause of death in the United States in
2014 (source: CDC). Approximately 117 people commit suicide
each day in the United States (43,000 per year). Many more people
attempt suicide. The overall suicide rate in the United States
increased 24% during the 15-year period from 1999 to 2014.
Although the rate of suicide in teenagers aged 15 to 19 is low
compared with the general adult population, the rate of teen suicide
has risen dramatically in the past 50 years.
RISK FACTORS
The overwhelming majority of people who commit suicide have a
mental illness (most often a mood disorder or chronic alcoholism).
The first-degree relatives of people who have committed suicide
are at a much higher risk of committing suicide themselves. Gay
and lesbian youth have two to three times the rate of attempted
suicide compared to heterosexual adolescents. Transgender
individuals have suicide attempt rates two to four times those of
cisgender individuals. Suicide risk increases with age. In men,
suicides peak after age 45; in women, most suicides occur after age
55. Elderly individuals account for 25% of the suicides, although
they represent only 10% of the population. Overall, men are more
successful at completing suicide, perhaps because of their more
lethal methods (shooting, hanging, and jumping). Men commit
suicide about four times as often as women, whereas women
attempt suicide about four times as often as men. Women often
overdose or attempt drowning. Married people have a lower risk of
suicide than singles. Suicide is more common among higher social
classes, whites, and certain professional groups (physicians,
dentists, musicians, law enforcement officers, lawyers, and
insurance agents). As noted, biologic risk factors include altered
serotonin markers. Among psychological risk factors, hopelessness
has been shown to be one of the most reliable indicators of long-
term suicide risk.
The available evidence suggests that suicidal risk may increase
in children, adolescents, and young adults less than 24 years old
who initiate treatment with antidepressant medication (for
depression or other psychiatric conditions). The details of the
association between antidepressant medication treatment and child
and adolescent suicidality are unknown. Antidepressant medication
prescribing information in the United States now contains a black
box cautioning providers to assess carefully the risks and benefits
of antidepressant treatment in children and adolescents. Providers
should also warn patients and their families that suicidal thinking
may increase with antidepressant medication treatment, especially
during the first few months of treatment. Because antidepressants
may also transiently increase suicidality in adults, these patients
should be cautioned regarding this possibility. Periods of initiating,
tapering, or adjusting the dosage of an antidepressant medication
may increase the risk of worsening depression or suicidality: these
periods warrant extra scrutiny by patients, families, and caregivers.
Two medications have thus far shown evidence for reducing
suicide risk: lithium, when used to treat bipolar disorder; and
clozapine, when used to treat schizophrenia. Abrupt lithium
discontinuation, however, is associated with a greatly increased
suicide risk for at least 1 year afterward. As such, physicians
should very carefully consider the potentially fatal delayed
consequences of psychiatric medication changes, especially for
lithium and similar mood stabilizers until additional data are
available on the safety of these practices.
Most often, a suicide attempt is self-evident at presentation, either
because the patient or family indicates that such an event has
occurred or because there is an acute medical or surgical
emergency (i.e., overdose or wrist laceration). It is important
always to obtain further details from the patient and any witnesses
to provide a full history of the antecedents and the suicidal act.
Occasionally, a patient will present to a physician in a more subtle
way, with nonspecific complaints. Patients may also overtly deny
suicidal intent, even when prior statements to intimates or
caregivers indicate clear suicidal thinking or planning. Careful
enquiry may reveal that the patient has taken an overdose of a
medication with delayed lethality (such as acetaminophen).
Patients who have attempted suicide require thorough
psychiatric evaluation. Psychiatric history and mental status
examination should explicitly address depressive symptoms, such
as suicidal thoughts, intent, and plans. The details of the suicide
attempt are critical to understanding the risk of a future suicide.
Patients who carefully plan the attempt, use particularly violent
means, and isolate themselves so as not to be found alive are at
particularly high risk of future suicide completion.
Patients who attempt suicide most commonly suffer from
depression, schizophrenia, alcoholism, or personality disorders (or
a combination of these disorders). Patients who do not meet criteria
for any of these disorders can and do attempt or commit suicide,
however, especially if they have any of the risk factors (e.g.,
hopelessness).
MANAGEMENT
Suicidal ideation should always be taken seriously. Suicidal
patients are often fraught with ambivalence over whether to live or
die, and intervention and effective treatment can be lifesaving. In
many cases, these patients require intensive observation on a secure
inpatient unit with ligature-free fixtures for their own safety.
Potentially lethal items should be held securely by nursing staff,
and the patient should be observed carefully for the risk of
elopement. Treatment of the underlying disorder or distress derives
from accurate diagnosis: antidepressants or electroconvulsive
therapy for depression and antipsychotics and/or mood stabilizers
for bipolar disorder, psychotic depression, or schizophrenia. Often,
the hospitalization and the ensuing attention can give some patients
hope of improvement long before biologic therapies have had an
impact, thereby acutely decreasing hopelessness and suicidal
thoughts.
Patients at lower risk of suicide or who are meaningfully
engaged in treatment can be managed as outpatients if close
follow-up is available, family members are supportive, and a
treatment alliance exists. Frequent meetings with treatment
providers, eliminating the means of suicide (firearms, potentially
toxic prescription pills), and enlisting spouses, partners, or other
family members are essential elements of outpatient treatment.
Surprisingly, there is little solid empirical evidence to guide
clinical intervention targeted at preventing suicide. Although it
seems clear that treating an underlying psychiatric condition might
reduce the suicide risk associated with that condition, clear data are
not yet available regarding the particular efficacy of a given
medication or class in this regard (except for lithium and
clozapine). Psychosocial interventions targeted at preventing
suicide do not have strong research support. Until additional
evidence-based findings emerge, the standard of care for suicidal
individuals remains hospitalization or other secure treatment
alternatives coupled with treatment of associated psychiatric
conditions.
INTIMATE PARTNER VIOLENCE

Abuse between spouses or partners can take several forms:
physical, sexual, and emotional. Physical abuse or battering is most
often perpetrated by a male on a female partner, but women do
batter men, and abuse also occurs in same-sex relationships.
EPIDEMIOLOGY
Intimate partner violence is estimated to occur in one-third of
women and around 25% in men. Some studies estimate that nearly
one-third of all women have been beaten by their husband at least
once during their marriage. Many battered women are eventually
murdered by their spouses or boyfriends. According to the U.S.
Department of Justice, 37% of women treated in emergency rooms
for violent injuries were hurt by a current or former partner. Of
women murdered by an intimate partner, 44% visited an
emergency room in the 2 years before their death.
RISK FACTORS
There is a strong association between alcohol abuse and domestic
violence. More than 50% of abusers, and many of the abused, have
a history of alcohol or other drug abuse. As children, most abusers
lived in violent homes where they either witnessed or were
themselves victims of battering. The victims of abuse, more often
than not, are also products of violent homes. Pregnant women are
at elevated risk for spousal abuse, often directed at their abdomens.
History and Physical and Mental Status Examination
Many victims of abuse are reluctant to report abusive episodes
because they fear retaliation, believe they are deserving of abuse,
or do not believe that help will be effective. Victims of abuse are
often mistreated in ways that prevent them from escaping the
abusive relationship. They are intimidated, maligned, coerced, and
isolated by the abuser. Attempts to leave an abusive relationship
may be thwarted by financial concerns, the welfare of children, fear
of being alone, or the threat of further battering.
Patients may present in the company of their abuser for the
treatment of “accidental” lacerations, contusions, fractures, or more
severe trauma. Unless the patient is asked tactfully in the absence
of the abuser, he or she is unlikely to reveal the true cause of
injuries.
Physical examination should include examination of the skin
for contusions (especially of the face and breasts) and a genital
examination. The mental status examination should take into
account the appropriateness of the patient’s and partner’s reactions
to the “accident.”
MANAGEMENT
The goal of treatment is to end the violence (i.e., both partners must
agree to treatment) or to enable the victim to leave the relationship.
Either option is difficult to achieve. Social agencies must be
enlisted to aid in child protection and custody if the latter option is
chosen.
Patients who refuse help should be told what emergency
services are available and how to access them. Unfortunately,
women are most at risk for serious injury or homicide when they
attempt to leave the abusive relationship.
ELDER ABUSE
Approximately 10% of those older than age 60 are abused. Victims
usually live with their assailants, who are often their children.
Mistreatment includes abuse and neglect and takes physical,
psychological, financial, and material forms. The abuser may
withhold food, clothing, or other necessities or beat, sexually
molest, or emotionally abuse the victim.
As with spousal abuse, the elder person is often reluctant to
reveal the abuse. Clinicians should be alert to the signs of abuse.
Treatment involves appropriate medical and psychiatric services
and social and legal services. Some states mandate reporting of
elder abuse.
BEREAVEMENT
Bereavement occurs following the death of a loved one. The
Diagnostic and Statistical Manual of Mental Disorders, 5th edition
(DSM-5) includes a condition called persistent complex
bereavement disorder for additional study. Persistent complex
bereavement disorder may be diagnosed if bereavement lasts
longer than a 12-month period in adults or a 6-month period in
children, following the loss of a loved one. The symptoms of
bereavement, such as sad mood, trouble sleeping, loss of appetite,
and ruminating on the loss of the loved one, mimic to some degree
those of major depression. When symptoms of major depression
predominate, however, or when the following symptoms occur, a
diagnosis of major depression should be considered. Symptoms
suggesting major depression include the following:
1. Increased guilt (not associated with behavior or actions related

to the death of the loved one)
2. Suicidal thinking or thoughts of death (other than feeling that
one has a desire to join the loved one in death)
3. Excess worthlessness
4. Psychomotor retardation
5. Severe impairment in ability to function
6. Auditory or visual hallucinations (other than hearing the voice
or image of the deceased, which is considered a normal
component of bereavement)
Treatment for bereavement is diverse, and there is not sufficient

evidence available to suggest that one form of therapeutic
intervention is reliably superior to another. In bereaved individuals
with depression, antidepressant medication is indicated.
KEY POINTS
Suicide is a fatal complication of many psychiatric
disorders.
Hopelessness is a risk factor for attempting
suicide.
Antidepressants may transiently increase the risk
of suicide.
About one-third of women suffer intimate partner
violence.
About 10% of individuals over age 60 suffer elder
abuse.
Antidepressant medications are indicated for the
treatment of depression in bereaved individuals.
CLINICAL VIGNETTES
VIGNETTE 1
You are a volunteer answering a mental health crisis hotline. Late one
evening, you receive a call from an unidentified male located in the
rural counties who tells you that he “just needed someone to talk to.”
You notice that his voice sounds sad and flat. Further history reveals
that his wife died 1 year ago today. You proceed to complete a suicide
risk assessment.
1. Which of the following is a risk factor for suicide?

a. African American race
b. Dependent children in the home
c. Full-time employment
d. Male gender
e. Strong religious faith
2. Which neurotransmitter has been most strongly implicated in

suicide?
a. Acetylcholine
b. Dopamine
c. Norepinephrine
d. Serotonin
e. Melatonin
3. Which of the following medication has emerging evidence for

reducing suicide?
a. Clozapine
b. Lithium
c. Ketamine
d. Alprazolam
e. Haloperidol
VIGNETTE 2
A 23-year-old man is psychiatrically evaluated in the surgical intensive
care unit after sustaining a self-inflicted gunshot wound to the
abdomen. The patient is conscious but sedated following surgical
intervention. On examination, the patient is vague and guarded. He
provides a history that he was not suicidal and that he accidentally
shot himself while cleaning the gun. He admits to drinking a few beers
before the incident.
1. At this point, the next step in properly evaluating this patient is:
a. To accept the patient’s assertion that the event was accidental
b. To obtain a head computed tomography (CT)
c. To obtain a thyroid-stimulating hormone level
d. To refer the patient to Alcoholics Anonymous
e. To obtain additional history from the patient and family, friends,
or witnesses to the event
2. Additional history obtained from a close friend reveals that the

patient had been despondent over a romantic breakup and
worsening performance in college. The patient did not ingest
alcohol routinely, but he had drunk to the point of intoxication at
least twice in the past week. The patient’s family reported that he
had been avoiding them over the past few days. Based on the
additional history, it seems reasonable to:
a. Accept the patient’s assertions that the gunshot was accidental
b. Discuss your findings with the patient and explain that you are
concerned about the possibility of a suicide attempt
c. Discuss the patient’s alcohol abuse with the patient
d. Keep your findings secret from the patient so as not to provoke
anger at his friends and family
e. Initiate pharmacologic treatment with an antidepressant
medication
ANSWERS
1. Answer D:
Men are more successful at completing suicide than are women,
possibly because they are more likely to use methods of higher
lethality such as shooting or jumping rather than overdose or
drowning. Suicide is more common in Caucasians than in African
Americans. Living with dependent children, being employed, and
religious faith are protective factors against suicide.
2. Answer D:
There is considerable evidence that altered central nervous system
serotonin is associated with increased suicide risk. Altered serotonin
markers include reduced cerebrospinal fluid serotonin metabolites,
reduced brain serotonin concentration, increases in numbers of
brainstem serotonin neurons, the serotonin transporter, and serotonin
1A receptors. Alterations in the tryptophan hydroxylase gene, a key
enzyme in serotonin synthesis, have been associated with suicide
risk. Other factors, including reductions in norepinephrine neurons,
reduced brain volume in prefrontal cortical regions, increased
peripheral inflammation, and alterations in the hypothalamic–pituitary–
adrenal axis have also been implicated.
3. Answer C:
Ketamine has shown early promise in clinical trials in rapidly reducing
suicidal ideation and depressive symptoms. More study is needed but
ketamine or a related compound is expected to emerge as a novel
treatment for suicidal ideation and depression. Clozapine has a well-
established efficacy in reducing suicidal behavior in individuals with
psychosis. Lithium has a well-established efficacy in reducing suicidal
behavior in mood disorders. Alprazolam and haloperidol are often
used in the treatment of anxiety and psychosis, respectively, but have
not been proven to have specific effects on reducing suicidality.
1. Answer E:
The described vignette is commonly seen in patients who attempt
suicide. To accept the patient’s assertion that the event was
accidental would be inappropriate in the face of a life-threatening
event. Patients often attempt suicide and then deny any intention to
self-harm. Intoxication with alcohol or other drugs is common. A head
CT does not appear clinically indicated unless one suspects head
injury or intracranial process predisposing to self-injurious behavior. A
thyroid-stimulating hormone level might be appropriate if the patient is
found to have depression. The patient may have alcohol dependence
or abuse warranting a referral to Alcoholics Anonymous, but the
available history does not support such a diagnosis at this point.
Obtaining additional history is critical for properly evaluating this
patient. In such cases, collateral history of prior suicidal statements to
family or friends is often uncovered. Or, behavioral change consistent
with a diagnosis of depression may be found. Denial or ambivalence
regarding suicide attempts is frequently present.
2. Answer B:
Discuss your findings with the patient and explain that you are
concerned about the possibility of a suicide attempt. Forming a
treatment alliance with the patient is the best path to obtaining
additional information from him and helping him gain insight into his
circumstances. In the clinical setting, it is often unclear whether
patients who attempt and then deny self-injury in the context of clear
psychosocial stress and vocational and interpersonal difficulties are
conscious of their suicidal intentions. Denial of suicide attempts is
quite common; however, and the use of intoxicants before such
attempts is also a common clinical scenario. A discussion of alcohol
use and misuse is also important, but the most urgent medical
consideration at this point is suicidality. An antidepressant would be
indicated if additional history supported the diagnosis of major
depression.
Legal issues affect all areas of medicine, including psychiatry. The
laws that govern medical practice address physician duty,
negligence, and malpractice, as well as patient competence or
capacity, consent, and right to refuse treatment. Previous court
decisions, or precedents, are used as the standard by which a given
action (or inaction) is judged. Practitioners should be aware of the
pertinent laws of the state in which they practice, to comply
adequately with standards of practice, while respecting the rights
and duties of their role. Reducing adverse events and legal claims
in the health care system is known as risk management.
MALPRACTICE
The legal definition of malpractice requires the presence of four
elements: negligence, duty, direct causation, and damages.
Negligence can be thought of as failure to perform some task with
respect to the patient, falling short of the care that would be
provided by the average practitioner (the standard of care). Duty
reflects the law’s recognition of the physician’s obligation to
provide proper care to his or her patients. This definition of duty of
care requires the presence of a doctor–patient relationship. Direct
causation requires that the negligence directly caused the alleged
damages. Finally, damages (e.g., physical or emotional harm) must
in fact be shown to have occurred. In short, malpractice involves
the negligence of a duty that directly causes damages. Malpractice
claims in psychiatry principally involve suicides of patients in
treatment, misdiagnosis, medication complications, false
imprisonment (involuntary hospitalization or seclusion), and sexual
relations with patients.
INFORMED CONSENT
Informed consent has three elements: information, capacity, and
consent. First, appropriate levels of information regarding a
proposed treatment, including side effects, alternative treatments,
and outcome without treatment, must be provided (the process of
informing or disclosing). Second, the patient must have capacity,
that is, possess the ability to understand, appreciate, reason, and
express a choice (make decisions) regarding the risks and benefits
of treatment. Having capacity requires more than simply repeating
information and necessitates that a person demonstrate
comprehension and flexible manipulation of the information in the
context of a specific decision. Third, the patient must give consent
voluntarily (important to the concept of volition is the lack of
subtle or overt coercion). The elements of informed consent and
capacity are depicted in Figure 14-1. True emergency situations are
an exception to this rule; treatments necessary to stabilize a patient
in an emergency can be given without informed consent.
(Commonly, the word capacity is used to describe a patient or
research volunteer’s ability to make a treatment or research
participation decision. Competence generally refers to the findings
of a judicial or other legal proceeding regarding a person’s ability
to consent. The two terms are sometimes used interchangeably,
however.) It is important to realize that individuals who have
psychiatric disorders such as major depression, mild dementia, or
schizophrenia may still retain capacity to consent to treatment or
research interventions. All that is required is that a person meets
the aforementioned criteria for capacity.
FIGURE 14-1. The elements of informed consent and capacity.
INVOLUNTARY COMMITMENT
Commitments are generally judicially supported actions that
require persons to be hospitalized or treated against their will.
Although laws vary from state to state, commitment criteria usually
require evidence that the patient is a danger to self, a danger to
others, or is unable to care for him or herself. Psychiatrists, in most
localities, have the right to commit a patient, temporarily and
involuntarily, if any of these criteria are met and a diagnosis of a
mental disorder is provided (in other words, both a mental disorder
and danger must exist). The duration of temporary commitment
and the rights of the patient vary by jurisdiction. Patients who have
been committed have a right to be treated. Regulations for
obtaining authorization to treat patients against their will vary by
state although forced treatment is usually permitted in emergency
situations.
THE TARASOFF DECISIONS: DUTY TO WARN

(OR PROTECT)
Tarasoff v The Board of Regents of the University of California (or
simply, Tarasoff ) was a landmark case that was heard twice in the
California Supreme Court. Tarasoff I (1976 ruling) held that
therapists have a duty to warn the potential victims of their patients
when patients express a desire to harm a specific person. Tarasoff
II (1982 ruling) held that therapists have a duty to take reasonable
steps to protect potential victims of their patients. In most
localities, this means that the therapist should take reasonable
action to protect a third party if a patient has specifically identified
the third party and a risk of serious harm seems imminent.
Protection may be defined by specific state law or prevailing legal
interpretation, but it may include hospitalizing the patient, altering
treatment, warning the intended victim or victims, notifying the
police, and so on. There are many different legal interpretations,
however, of the duty to warn. Such varying interpretations of
physicians’ responsibilities regarding the balance between
confidentiality and protecting others create great difficulty in
psychiatric practice. Because the specific legal requirements vary
by state law, it is important to understand the requirements of each
jurisdiction.
M’NAGHTEN RULE: THE INSANITY DEFENSE

Named after a mentally ill man (Daniel M’Naghten) who attempted
to assassinate the prime minister of England in 1843, this rule
forms the basis of the insanity defense. According to the
M’Naghten rule, a person is not held responsible for a criminal act
if at the time of the act he or she suffered from mental illness or
mental retardation and did not understand the nature of the act or
realize that it was wrong. In more recent history, the appropriate
use of the insanity defense has been called into question. Some
legal theorists argue for the designation “guilty but insane” to
indicate culpability but at the same time recognize the presence of a
mental illness (and presumably the need for treatment).
MANDATORY REPORTING
Requirements for physicians to conduct mandatory reporting vary
by state, but may include reporting child abuse, elder abuse,
domestic violence, and impaired colleagues. Most commonly,
reporting of child physical or sexual abuse and elder abuse or
neglect is mandated. In some jurisdictions, reporting of impaired
physicians or other professional colleagues may be required.
KEY POINTS
Malpractice consists of negligence, duty, direct
causation, and damages.
The essential elements of informed consent are
information, capacity, and consent.
The Tarasoff decision led to an expectation that
therapists and doctors take reasonable action to
protect persons whom their patients have
specifically threatened.
The M’Naghten rule is the basis of the insanity
defense.
CLINICAL VIGNETTES
VIGNETTE 1
An 88-year-old woman is brought into the emergency room by her
daughter because of a change in her mental status. She had been
previously doing well until she was left at home with her daughter’s
husband for a week while the daughter was away on business. You
examine her and order a head CT. The head computed tomography
(CT) reveals a subdural hematoma that appears to be less than a
week old. There is also soft tissue swelling over her cranium and
around her jaw. You suspect elder abuse and order a radiograph
series looking for other fractures. The radiograph series reveals
several recent fractures of the ribs and long bones of her body.
1. After consulting a neurosurgeon about the need for subdural

drainage, the next best step is to:
a. Call the risk management officer for the hospital
b. Coordinate with social services to submit a report of suspected
elder abuse
c. Call the son-in-law at home and confront him
d. Call the local police to have the daughter arrested
e. Refer her back to her primary care physician and send her
home
VIGNETTE 2
A physician is very attentive and compassionate with his patients. One
of his patients sustains a permanent injury that would not have
occurred if the physician had made the correct diagnosis. The
physician finished his residency more than 20 years ago, and the
diagnosis has only been well established for the past 5 years. On
questioning, the physician is unaware of the diagnosis. You are asked
to review the case.
1. Which of the following elements is evidenced by this physician’s

unfamiliarity with the diagnosis?
a. Duty
b. Direct causation
c. Damages
d. Failure to meet standard of care
e. Poor risk management
VIGNETTE 3
You are working in an outpatient psychotherapy clinic when your
patient tells you that she plans to kill her landlord. The patient calls the
landlord by name and mentions that he lives just down the street from
her. You tell the patient that you are quite concerned about these
homicidal feelings and recommend inpatient psychiatric admission.
Before you can react, the patient bolts from the office and escapes.
You realize that you must attempt to warn the patient’s landlord about
the patient’s statements.
1. Your actions are grounded in which of the following legal

precedents?
a. The Tarasoff decision
b. The M’Naghten rule
c. Griswold v. Connecticut
d. Swedish Common Law
e. Negligence
ANSWERS
1. Answer B:
This patient’s presentation is highly suggestive of elder abuse with
multiple fractures and injuries. Suspected cases of elder abuse need
to be reported in many states and social workers usually know the
specific procedure for reporting because there may be institutional and
state and local requirements. However, a physician should verify the
follow through on reporting to ensure that reporting requirements have
been satisfied. Sending the patient home and arranging for outpatient
follow-up leaves the patient at significant risk and violates mandated
reporting laws in many states. Although it may be tempting to confront
the suspected perpetrators, it is generally better to leave this in the
hands of experienced workers who can sort out the social situation
and report the appropriate persons to authorities.
1. Answer D:
Malpractice requires the presence of four elements: negligence, duty,
direct causation, and damages. Negligence includes failing to meet
the standard of care. Negligence can be thought of as failure to
perform some task with respect to the patient, falling short of the care
that would be provided by the average practitioner (the standard of
care). Duty reflects the law’s recognition of the physician’s obligation
to provide proper care to his or her patients. This definition of duty of
care requires the presence of a doctor–patient relationship. Direct
causation requires that the negligence directly caused the alleged
damages. Damages (e.g., physical or emotional harm) must in fact be
shown to have occurred. In short, malpractice involves the negligence
of a duty that directly causes damages. Malpractice claims in
psychiatry principally involve suicides of patients in treatment,
misdiagnosis, medication complications, false imprisonment
(involuntary hospitalization or seclusion), and sexual relations with
patients.
1. Answer A:
The Tarasoff decisions held that therapists have a reasonable duty to
warn potential victims of threats made by patients in treatment.
Although there are many different legal interpretations of this decision
(also called the duty to warn or protect), it is important for practicing
physicians to know the rules in their jurisdiction. The M’Naghten rule
refers to the insanity defense. Griswold v. Connecticut is a landmark
Supreme Court case related to birth control but is not relevant to
medical decision making. The duty to warn is based on initial rulings
by the California Supreme Court and is not based on Swedish
Common Law. Negligence is an element of medical malpractice,
which could be incurred if a physician failed to meet the standard for
the duty to warn.
Antipsychotic medications are used commonly in medical and
psychiatric practice. As a class, antipsychotics have in common
their blockade of dopamine receptors and their potential for serious
side effects if used inappropriately or without careful monitoring.
The most commonly prescribed typical (first generation)
antipsychotics and atypical (second generation) antipsychotics are
listed in Tables 15-1 and 15-2. Their relative potencies, side-effect
profiles, and major adverse reactions are also described.
TABLE 15-1. Typical Antipsychotics

Drug Therapeutic Potencyb Sedative Hypotensive Anticholiner
Dosage
Rangea
(mg)
Typical antipsychotics (dopamine antagonists)
Thioridazine 150–800 100 High High High
(Mellaril)
Chlorpromazine 200–800 100 High High Med
(Thorazine)
Molindone 15–255 10 Med Low Med
(Moban)
Perphenazine 8–32 10 Low Low Low
(Trilafon)
Loxapine 60–100 10 Med Low Med
(Loxitane,
Daxolin)
Trifluoperazine 5–20 5 Med Low Low
(Stelazine)
Thiothixene 5–30 5 Low Low Low
(Navane)
Haloperidol 5–30 2 Low Low Low
(Haldol)
Fluphenazine 2–60 2 Med Low Low
(Prolixin)
Pimozide 15–225 1 Low Low Low
(Orap)
aRecommended initial starting dosages are lower than the therapeutic dosage. Dosages are generally lower for geriatr
interacting medications or have other medical problems.
bPotency is indicated as relative milligram dose equivalents (i.e., 100 mg of thioridazine is equivalent to 2 mg of halo
confused with efficacy. All typical antipsychotics are thought to be equally efficacious.
Based on Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock’s Synopsis of Psychiatry, 11th ed. Philadelphia, PA: W
TABLE 15-2. Atypical Antipsychotics

Drug Therapeutic Daily Dosage Range (mg)
Aripiprazole (Abilify) 10–30
Asenapine (Saphris) 5–20
Brexpiprazole (Rexulti) 2–4
Cariprazine (Vrylar) 1.5–6
Clozapine (Clozaril) 100–900
Iloperidone (Fanapt) 12–24
Lurasidone (Latuda) 40–160
Olanzapine (Zyprexa) 10–20
Paliperidone (INVEGA) 3–12
Quetiapine (Seroquel) 400–750
Risperidone (Risperdal) 4–16
Ziprasidone (Geodon) 80–160
Based on Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock’s Synopsis of Psychiatry, 11th ed.
Philadelphia, PA: Wolters Kluwer, 2015.
Both typical antipsychotics and atypical antipsychotics are

generally equally effective, although they differ in side-effect
profiles and potencies. Typical antipsychotics have a tendency to
have greater risk for extrapyramidal side effects at therapeutic
doses as compared to atypical antipsychotics. Clozapine, the first
antipsychotic to be recognized as “atypical,” is considered more
effective than typical antipsychotics for the treatment of refractory
psychotic disorders.
INDICATIONS
Antipsychotics are generally effective in treating the positive
symptoms of schizophrenia (e.g., hallucinations, bizarre behavior,
delusions) regardless of the actual diagnostic category (Table 15-
3). For example, hallucinations in schizophrenia, in Alzheimer’s
disease, or secondary to cerebral toxicity or injury all respond to
antipsychotic medications. Typical antipsychotics are thought to be
less effective than atypical antipsychotics in treating the negative
psychotic symptoms of schizophrenia (e.g., amotivation, akinesia,
affective blunting, and social withdrawal). In addition to their role
in treating psychotic symptoms, antipsychotics are used to treat
bipolar disorder, some forms of nonpsychotic behavioral
dyscontrol (e.g., organic brain syndromes, Alzheimer’s disease,
mental retardation), delirium, Tourette’s syndrome, posttraumatic
stress disorder symptoms, and transient psychotic symptoms
because they appear in patients with personality disorders.
TABLE 15-3. Indications for Antipsychotic Drugs

Effective Possibly Effective
Short- Exacerbations of Brief use for episodes of severe
term schizophrenia behavioral dyscontrol or
use (<3 Acute mania apparent psychosis in some
months) Psychotic depression personality disorders
Brief psychotic disorder
Acute delirium
Drug-induced psychoses
resulting from hallucinogens
and psychostimulants (not
phencyclidine)
Long- Schizophrenia Delusional disorders
term Tourette’s syndrome Childhood psychoses
use (>3 Bipolar disorder Post traumatic stress disorder,
months) Huntington’s disease nightmares, and flashbacks
Chronic psychoses related to
neurologic disorders
Based on Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock’s Synopsis of Psychiatry, 11th ed.
Philadelphia, PA: Wolters Kluwer, 2015.
MECHANISM OF ACTION
The most prominent theory on the mechanism of action of
antipsychotics is the dopamine hypothesis of schizophrenia. This
hypothesis purports that dopaminergic hyperactivity leads to
psychosis (Fig. 15-1). For example, drugs that are dopamine
agonists, such as amphetamines or cocaine, can produce psychotic
syndromes that look very similar to schizophrenia, whereas all
antipsychotic drugs block dopamine receptors which assist in
treating the positive symptoms of psychosis. The use of
medications/drugs to produce either hyper- or hypodopaminergic
states that exacerbate or quell psychotic symptoms is the basis of
the dopamine hypothesis of schizophrenia.
Although dopamine physiology is critical in the understanding
of psychotic disorders, it is only part of a much more complex
underlying pathology. Abnormalities in γ-aminobutyric acid
(GABA) and N-methyl d-aspartate (NMDA) receptors and cortical
neural networks are present in patients with schizophrenia versus
healthy controls. A comprehensive neurophysiologic model of the
disorder is being developed via the synthesis of a growing
scientific knowledge base.
A third generation of antipsychotics is likely to be developed on
the basis of discoveries of the therapeutic effects of GABA and
NMDA modulation.
In addition, the action mechanisms of current antipsychotics are
often much broader than simple dopamine blockade, which
accounts for the numerous side effects and the finding that their
action in the brain is not well correlated with regions thought to
give rise to psychotic symptoms. The atypical antipsychotic
medications, in addiction to dopamine antagonism, have prominent
serotonin (5-hydroxytryptamine-2) receptor blockade. It is unclear
whether this serotonin activity imparts antipsychotic efficacy, but
the activity may affect mood and anxiety symptoms in patients
with psychotic disorders and help prevent extrapyramidal side
effects.
Some atypical antipsychotics also appear to have “mood-
stabilizing” properties in bipolar disorder. It is unclear whether the
mechanism of these effects is related to dopamine, serotonin, or
some other chemical mechanism.
TYPICAL ANTIPSYCHOTICS (DOPAMINE

ANTAGONISTS)
The antipsychotic potency of antipsychotics correlates with their
affinity for the D2 receptor (see Fig. 1-1). Figure 15-2 is a
schematic diagram of the proposed brain pathways affected by
typical antipsychotics. Dopamine-containing axons arising from
brain stem nuclei (the ventral tegmental area and substantia nigra)
project to the basal ganglia, frontal cortex, and limbic areas.
Typical antipsychotic drugs and the atypical antipsychotic
risperidone strongly block D2 receptors. Blockade of dopamine in
the cortical and limbic areas results in reduction in psychotic
symptoms, whereas blockade of dopamine in the basal ganglia
produces extrapyramidal side effects. Thus, there is a narrow
window of efficacy versus side effects. Although antipsychotics,
especially lower potency medications, may have an initial sedative
effect, their antipsychotic action is not immediate and may take
several days to weeks to peak.
FIGURE 15-1. The dopaminergic diffuse modulatory systems of the

brain. The mesocorticolimbic dopamine system arises in the ventral
tegmental area and has been implicated in the cause of
schizophrenia. A second dopaminergic system arises from the
substantia nigra and is involved in the control of voluntary movement
by the striatum. (From Bear MF, Connors BW, Parasido MA.
Neuroscience: Exploring the Brain, 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins, 2015.)
FIGURE 15-2. Pathways affected by typical antipsychotics. VTA,

ventral tegmental area.
ATYPICAL ANTIPSYCHOTICS
(SEROTONIN/DOPAMINE ANTAGONISTS)
At present, in the United States, there are 10 approved atypical
antipsychotics. Antipsychotics are classified as atypical when they
produce fewer movement side effects than typical antipsychotics.
In addition to dopamine receptor blockade, atypicals block
serotonin (5-HT) receptors of the 5-HT2 subtype. Figure 15-3
depicts the similarities and differences of the serotonin and
dopamine systems. Serotonin receptor blockade conveys some
protection against extrapyramidal side effects and may impart
antipsychotic efficacy. Risperidone is similar to typicals in that it is
a very potent blocker of the D2 receptor with relatively low
serotonin blockade compared to other atypicals.
FIGURE 15-3. Pathways affected by atypical antipsychotics. VTA,

ventral tegmental area.
CHOICE OF MEDICATION
Antipsychotic medications are most commonly chosen for the
acute treatment of psychosis in both mood and psychotic disorders.
Choice of medication should be based on diagnosis, phase of the
illness, prior patient or family member response, side-effect profile
(patient tolerance), likelihood of adherence, and available form
(i.e., elixir, intramuscular, intravenous, or intramuscular depot).
The oral preparations of the atypical antipsychotics are usually
considered first line for acute psychosis. At present, clozapine is
the only antipsychotic medication clearly shown to be superior in
patients for whom other antipsychotics have failed. Because of
clozapine’s serious side effects, however, it is not used until
patients have failed at least two other antipsychotics. Intramuscular
forms of aripiprazole, olanzapine, and ziprasidone are available and
approved for acute agitation in schizophrenia. Intramuscular
haloperidol is not approved by the U.S. Food and Drug
Administration (FDA) for agitation associated with schizophrenia,
but it is frequently used off-label for this purpose given its low cost
and availability. Fluphenazine, haloperidol, risperidone,
paliperidone, aripiprazole, and olanzapine are available in depot (or
other long-acting) preparations, which are given intramuscularly
every 2 to 4 weeks for maintenance treatment of chronic psychosis
(e.g., chronic schizophrenia).
Choice of medication is often, but not required, to be guided by
approvals that have been obtained from the FDA. Much prescribing
is done “off-label” on the basis of available research and clinical
experience. The FDA approval process often lags behind state-of-
the-art psychopharmacology. Approved indications have become
increasingly specific, for example, specifying not only the
diagnosis but also the phase of the illness for which a drug is
approved (e.g., the manic phase of bipolar disorder). The
indications for some antipsychotics have recently broadened to
include the treatment of various phases of bipolar disorder even
when there is no psychosis present. Aripiprazole, asenapine,
chlorpromazine, olanzapine, quetiapine, risperidone, and
ziprasidone are all approved for use in the manic phase of bipolar
disorder. Olanzapine–fluoxetine in combination and quetiapine and
lurasidone are approved for treatment of bipolar depression.
A major multicenter clinical trial that aims to compare the
effectiveness of the antipsychotics to provide evidence to guide
treatment choice is under way. The study, known as the Clinical
Antipsychotic Trials of Intervention Effectiveness (CATIE)
schizophrenia trial, is being performed and published in phases
over years. The initial phases of the study have confirmed current
knowledge that antipsychotics are only partly effective in
populations of patients, particularly because of intolerable side
effects both in typicals and atypicals. The study has also shown that
the typicals (represented in the study by the midrange potency drug
perphenazine) and the atypicals (with the exception of clozapine)
have comparable rates of effectiveness as measured by rates of all-
cause discontinuation (less than one-third of patients remained on
any of the initial randomized drug at the end of the 18-month study
either because the first drug was intolerable or ineffective). The
side effects of the agents, however, have been shown to differ
markedly: movement disorder side effects are more common with
typicals; and sedation or metabolic effects more common with
atypicals. Phase 2 of CATIE revealed superiority of clozapine over
other atypicals in terms of all-cause discontinuation, with 44% of
the clozapine patients remaining on the drug at 18 months. Phase 3
allowed patients and providers to select their own medications.
Few patients chose typical antipsychotics and patients with the
highest weight chose aripiprazole and ziprasidone. There was no
significant difference in efficacy of the different treatments.
Aripiprazole did have the greatest increase in blood glucose, but
this may have been due to the population that selected the drug.
The medication pimavanserin (Nuplazid) is an atypical
antipsychotic that is approved for treating psychotic symptoms
(delusions and hallucinations) in Parkinson’s disease. The
recommended dose is 34 mg per day.
THERAPEUTIC MONITORING
Patients on antipsychotics should be monitored closely for adverse
drug reactions. Metabolic and neurologic reactions are particularly
important. It is now recommended that one obtain a baseline body
mass index and fasting blood glucose before initiating an atypical
antipsychotic because of the risk of weight gain and diabetes.
Neurologic disorders such as akathisia (restlessness), neuroleptic
malignant syndrome, and extrapyramidal symptoms can happen
with most antipsychotics, but these are more common with typical
antipsychotics. Patients taking any antipsychotic should be
carefully monitored for seizure activity, because all antipsychotics
appear to modestly lower seizure threshold with clozapine having
the greatest risk of seizure activity. Individuals taking clozapine
must have frequent checks of white blood cell counts to monitor for
the development of agranulocytosis. Clozapine must be
discontinued immediately in patients demonstrating this potentially
fatal reaction.
Blood levels have generally been of little use in monitoring
antipsychotic efficacy, but may be useful in assessing adherence.
Haloperidol levels have some utility in patients who have side
effects at low doses or who fail to respond to high doses. Clozapine
levels are also frequently used to determine adherence and correlate
efficacy with levels. Although approximately 40% of patients will
not respond to a particular antipsychotic, nonadherence (either full
or partial) is often the cause of apparent therapeutic failure.
The duration of therapy depends on the nature and severity of
the patient’s illness. Many disorders, such as schizophrenia, require
maintenance antipsychotic therapy. Because of the serious sequelae
associated with long-term antipsychotic use, maintenance therapy
should be used only after a careful risk-to-benefit analysis with the
patient and involved family.
SIDE EFFECTS AND ADVERSE DRUG REACTIONS

Side effects of antipsychotics are a major consideration in
physician prescribing. Patients who cannot bear the side effects of
medications are nonadherent and suffer greater rates of relapse and
recurrence of symptoms. Certain side effects such as sedation can
be useful to a patient with insomnia or severe agitation, but can
also limit functioning. A comparison of side-effect profiles for
commonly used typical antipsychotics is provided in Table 15-1.
Common side effects of typical and atypical antipsychotics are
described in the information to follow. Further discussion of
neurologic side effects is found in Chapter 20.
Anticholinergic Side Effects

Low-potency, typical antipsychotics (e.g., chlorpromazine) have
the greatest anticholinergic side effects such as dry mouth,
constipation, urinary retention, and blurred vision. In some cases,
anticholinergic delirium may occur, especially in elderly
individuals, those with organic brain syndromes, or patients on
other anticholinergic agents. Because extrapyramidal side effects
(e.g., muscle stiffness) are related to an imbalance between
dopamine and acetylcholine blockade, the typicals with high
anticholinergic activity and high antidopamine activity have low
incidence of extrapyramidal symptoms.
Reduced Seizure Threshold

Low-potency typical antipsychotics and clozapine are associated
with lowering seizure threshold. Seizures resulting from
antipsychotic therapy are treated by changing medications,
lowering the dose, or adding an antiepileptic medication.
Hypotension
Orthostatic hypotension is particularly common with low-potency
antipsychotics and risperidone. The hypotensive effect of
antipsychotics is generally caused by α-receptor blockade.
Agranulocytosis
Agranulocytosis has been associated most commonly with
clozapine. Because of the potentially fatal nature of this adverse
effect, clozapine distribution is regulated and requires a regular
complete blood count with absolute neutrophil count to monitor for
neutropenia.
Cardiac Side Effects

Thioridazine, mesoridazine, pimozide, ziprasidone, iloperidone,
and haloperidol may cause clinically significant QT prolongation.
Nonspecific electrocardiographic changes may also occur with
certain antipsychotic medications (particularly with clozapine and
olanzapine). Clozapine can cause myocarditis, which is rare, but
most commonly occurs early in treatment.
Metabolic Effects
Although patients with psychotic disorders are known to have
higher rates of obesity and diabetes mellitus independent of
medication therapy, studies have indicated that atypical
antipsychotic medications (particularly olanzapine and clozapine)
are associated with high rates of weight gain, dyslipidemia, and
may be associated with adult-onset diabetes.
Movement Disorders
Movement disorders such as dystonia, extrapyramidal symptoms,
akathisia, and tardive dyskinesia occur most commonly with high-
potency typical antipsychotics (e.g., haloperidol) and are discussed
further in Chapter 20.
Other Side Effects

Skin and ocular pigmentation are common side effects of
antipsychotics, as is increased photosensitivity. Thioridazine can
cause pigmentary retinopathy at high doses. Increased prolactin
levels (and sequelae) may also occur and is a particularly well-
known side effect in risperidone. Quetiapine may increase the risk
of developing cataracts.
KEY POINTS
Typical (first generation) and atypical (second
generation) antipsychotics are used to treat the
psychotic symptoms of a wide range of disorders.
Typical and atypical drugs appear to be equally
effective (with the exception of clozapine, which
may be the most effective for refractory
schizophrenia) but differ in D2 receptor potency
and side effects.
Antipsychotics can have serious neurologic and
metabolic side effects and should be carefully
prescribed and monitored.
CLINICAL VIGNETTES
VIGNETTE 1
A 20-year-old man with schizophrenia has recently had a change in
his antipsychotic medication in order to more effectively target
command auditory hallucinations. His dosage of haloperidol was
increased from 5 to 10 mg/day. His hallucinations are now well
controlled, but he is complaining of some muscular rigidity and
stiffness. You confirm the muscular rigidity and stiffness on physical
exam.
1. Which of the following agents would be an appropriate choice to

address this new problem?
a. Methylphenidate
b. Benztropine
c. Pemoline
d. Atenolol
e. Clonidine
2. The patient’s extrapyramidal symptoms improve but his

psychosis worsens and he requires inpatient hospitalization. On
review of his psychiatric history, you note that he has had multiple
trails of typical and atypical antipsychotics but has shown a
modest response to them at best and has required frequent
rehospitalization despite evidence that he has been largely
compliant with his prescribed medications. You start him on a
new medication and arrange to see him in follow-up. At his follow-
up appointment, his physical examination is normal. You counsel
him on smoking cessation and order a routine complete blood
count. Two days later, you notice that his absolute neutrophil
count came back at a low 900 per µL and it had been 6,500 per
µL at the last blood draw before starting the new medication. The
most likely antipsychotic agent the patient has been taking is:
a. Risperidone
b. Aripiprazole
c. Clozapine
d. Quetiapine
e. Thioridazine
ANSWERS
1. Answer B:
The patient described is experiencing extrapyramidal symptoms. The
first line of treatment for the symptoms is an anticholinergic agent. Of
all the agents listed, only benztropine is primarily an anticholinergic
medication. Methylphenidate and pemoline are both psychostimulants.
Atenolol is a β-blocker and may be used to manage blood pressure, to
treat akathisia (another side effect of psychotropic medications), and
in other conditions. Clonidine is primarily used as an antihypertensive
and is effective in the treatment of opiate withdrawal, attention-deficit
disorder, and Tourette’s syndrome.
2. Answer C:
The patient has moderate neutropenia. Although many medications
can cause neutropenia or agranulocytosis, clozapine carries the
highest risk of all the antipsychotics for this major adverse drug
reaction. Clozapine is indicated for the treatment of schizophrenia
when other medications have failed despite adequate trials. It is also
the only antipsychotic agent that requires frequent white blood cell
monitoring, and physicians are granted prescribing privileges for
clozapine only by taking part in prescriber certification. Clozapine has
other major risks including myocarditis and cardiomyopathy and also
lowers the seizure threshold.
Antidepressants are used commonly in medical and psychiatric
practice. As a class, antidepressants have in common their ability to
treat major depressive illness. Most antidepressants are also
effective in the treatment of panic disorder and other anxiety
disorders. Some antidepressants effectively treat obsessive–
compulsive disorder (OCD) and a variety of other conditions (see
indications to follow).
The most commonly prescribed antidepressants are listed in
Table 16-1. Antidepressants are subdivided into groups on the basis
of structure or prominent functional activity: selective serotonin
reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs),
monoamine oxidase inhibitors (MAOIs), and other antidepressant
compounds with a variety of mechanisms of action.
TABLE 16-1. Commonly Prescribed Antidepressants

Drug (Brand Name) Usual Daily Dosagea Extreme Daily
(mg) Dosagea (mg)
Selective serotonin reuptake inhibitors
Fluoxetine (Prozac) 20 80
Sertraline (Zoloft) 50–150 200
Paroxetine (Paxil) 20 50
Fluvoxamine 50–150 300
(Luvox)
Citalopram (Celexa) 20–40 40
Escitalopram 10 20
(Lexapro)
Serotonin-norepinephrine reuptake inhibitors
Venlafaxine 75–150 375
(Effexor)
Duloxetine 40–60 120
(Cymbalta)
Serotonin receptor agonists and antagonists
Trazodone (Desyrel) 200–400 600
Nefazodone 200–450 600
Norepinephrine-dopamine reuptake inhibitors
Bupropion 200–300 450
(Wellbutrin)
Tricyclic antidepressants
Nortriptyline 75–100 150
(Pamelor)
Amitriptyline 50–150 300
(Elavil)
Doxepin (Sinequan) 75–150 300
Imipramine 150–200 300
(Tofranil)
Desipramine 150–200 300
(Norpramin)
Protriptyline 15–40 40
Clomipramine 150–200 250
(Anafranil)
Trimipramine 50–150 300
Monoamine oxidase inhibitors
Selegiline (EMSAM 6–12 12
patch)
Tranylcypromine 30–50 60
(Parnate)
Phenelzine (Nardil) 45–60 90
Isocarboxazid 30–50 60
(Marplan)
Serotonin receptor antagonist/α-2 antagonist
Mirtazapine 15–45 45
(Remeron)
Multimodal antidepressants
Vortioxetine 5–20 20
(Trintellix)
Vilazodone 10–40 40
(Viibryd)
aGeriatric patients generally require lower dosages.
Choice of medications depends on diagnosis, history of

response (in patient or relative), lethality in overdose, and the side-
effect profile of the medication. Antidepressant effects are typically
not seen until 2 to 4 weeks into treatment. Side effects must be
carefully monitored, especially for TCAs and MAOIs.
INDICATIONS
Table 16-2 lists the indications for antidepressants. The main
indication for antidepressant medications is major depressive
disorder. Although specific indications vary, in general,
antidepressants are used in the treatment of all subtypes of
depression, psychotic depression (in combination with an
antipsychotic medication), atypical depression, and seasonal
depression (see Chapter 3), and bipolar depression when paired
with a specific mood stabilizer. Antidepressants are also indicated
for the prevention of recurrent depressive episodes.
TABLE 16-2. Indications for Antidepressants

Effective Major depressive disorder and other unipolar depressive
disorders
Bipolar depression (when paired with mood stabilizers)
Panic disorder
Posttraumatic stress disorder
Obsessive–compulsive disorder (e.g., clomipramine and
SSRIs)
Depression with psychotic features in combination with an
antipsychotic drug
Bulimia nervosa
Fibromyalgia and neuropathic pain (tricyclic drugs and
SNRIs)
Insomnia (e.g., trazodone, amitriptyline)
Enuresis (imipramine best studied)
Atypical depression (e.g., monoamine oxidase inhibitors)
Smoking cessation (e.g., bupropion)
Attention-deficit disorder with hyperactivity (e.g.,
desipramine, bupropion)
Probably Narcolepsy
effective Organic mood disorders
Pseudobulbar affect (pathologic laughing and weeping)
Possibly Personality disorders
effective
SNRIs, serotonin-norepinephrine reuptake inhibitors; SSRIs, selective serotonin reuptake inhibitors.
Modified from Labbate LA, Fava M, Rosenbaum JF, et al. Handbook of Psychiatric Drug Therapy,
6th ed. Philadelphia, PA: Wolters Kluwer, 2015.
Antidepressant medications are effective in the treatment of

patients with persistent depressive disorder, especially when there
are clear neurovegetative signs or a history of response to
antidepressants.
Panic disorder with or without agoraphobia has been shown to
respond to SSRIs, MAOIs, TCAs, and high-potency
benzodiazepines (alprazolam and clonazepam).
OCD has been shown to respond to the serotonin-selective
tricyclic clomipramine (Anafranil) and to SSRIs at high doses (e.g.,
fluoxetine at 60 to 80 mg per day). Obsessions tend to be more
responsive to pharmacotherapy than to compulsions. Symptoms of
OCD respond more slowly than do symptoms of major depression.
Trials of 12 weeks or more are needed before a medication can be
ruled a failure for a patient with OCD.
The binging and purging behavior of bulimia has been shown to
respond to SSRIs, TCAs, and MAOIs in several open and
controlled trials. Because SSRIs have the most benign side-effect
profile of these medications, they are often the first-line
psychopharmacologic treatment.
MECHANISMS OF ACTION
Antidepressants are thought to exert their effects at particular
subsets of neuronal synapses throughout the brain. Their major
interaction is with the monoamine neurotransmitter systems
(dopamine, norepinephrine, and serotonin). Dopamine,
norepinephrine, and serotonin are released throughout the brain by
neurons that originate in the ventral brain stem, locus coeruleus,
and the raphe nuclei, respectively (Figs. 15-1 and 16-1). These
neurotransmitters interact with numerous receptor subtypes in the
brain that are associated with the regulation of global state
functions including appetite, mood states, arousal, vigilance,
attention, and sensory processing.
FIGURE 16-1. Serotonin and norepinephrine neurons in the brain
stem project diffusely to innervate the entire brain. Serotonin axons
arise from serotonergic cell bodies located in the raphe nuclei.
Norepinephrine axons arise from noradrenergic cell bodies in the
locus coeruleus. (From Bear MF, Connors BW, Paradiso MA.
Neuroscience: Exploring the Brain, 4th ed. Philadelphia, PA: Wolters
Kluwer, 2015.)
SSRIs act mainly by binding to presynaptic serotonin reuptake

proteins, thereby inhibiting reuptake and increasing the levels of
serotonin in the synaptic cleft. TCAs act primarily by blocking
presynaptic reuptake of both serotonin and norepinephrine. MAOIs
act largely by inhibiting the presynaptic enzyme (monoamine
oxidase) that catabolizes norepinephrine, dopamine, and serotonin,
thereby increasing the levels of these neurotransmitters
presynaptically. These immediate mechanisms of action are not
sufficient to explain the delayed antidepressant effects (typically 2
to 4 weeks). Other, unknown mechanisms must play a role in the
successful psychopharmacologic treatment of depression.
Antidepressants and electroconvulsive therapy (ECT) are known to
increase levels of brain-derived neurotrophic factor (BDNF) in the
hippocampus in animal models. Antidepressants and ECT also
increase plasma levels of BDNF in humans, suggesting that
increased BDNF is a potential mechanism of antidepressant
treatment action.
Despite some studies indicating that some antidepressants are more
capable of producing remission, the majority of the evidence
indicates that all antidepressants have roughly the same efficacy in
treating major depressive episodes. Studies historically used
response as measured by a depression rating scale to
antidepressants; more recent studies have more strictly looked at
remission. Higher rates of remission may be achieved with
combinations of antidepressants. There are several treatment
algorithms available for the pharmacologic treatment of depression.
More research must be done in this area to determine the relative
rates of depression remission, particularly in subtypes of patients
with depression. SSRIs, bupropion, duloxetine, venlafaxine, and
mirtazapine are the most well-tolerated antidepressants and are
generally thought of as first-line agents for major depression.
Compared with TCAs and MAOIs, these medications have low
sedative, anticholinergic, and orthostatic hypotensive effects.
SSRIs, bupropion, duloxetine, venlafaxine, and mirtazapine should
be considered for use especially in patients with cardiac conduction
disease, constipation, glaucoma, or prostatic hypertrophy.
Antidepressants are relatively contraindicated in the manic or
mixed episodes of bipolar disorder and when used without
concomitant therapy with a mood stabilizer or antipsychotic.
Among the TCAs, nortriptyline and desipramine have the least
sedative, anticholinergic, and orthostatic hypotensive effects. They
can be used as first-line agents in younger, healthier people
especially if cost is a consideration (tricyclics and other
antidepressants available in generic form can be much less costly
than newer, nongeneric medications).
Because of the necessary diet restrictions and the risk of
postural hypotension, the traditional MAOIs (phenelzine and
tranylcypromine) should be used most selectively. They can be
quite effective, however, and are used in patients for whom SSRIs
and tricyclics have failed, in patients with a concomitant seizure
disorder (MAOIs and SSRIs do not lower the seizure threshold), or
in those with atypical depressions or social phobia (MAOIs or
SSRIs are most effective). High-dose SSRIs and clomipramine
(despite its high sedative, anticholinergic, and orthostatic
hypotensive effects) are the treatments of choice for OCD. A new
skin patch preparation of a previously available MAOI, selegiline,
is available and has demonstrated efficacy in treating depression.
Interestingly, at its usual daily dosage of 6 mg, dietary restrictions
are not necessary.
Approximately 50% of patients who meet criteria for major
depression will recover with a single adequate trial (at least 6
weeks at a therapeutic dosage) of an antidepressant. The most
common reasons for failed trials are inadequate dose and
inadequate trial length; however, dosage and length of trial are
often limited by side effects (or noncompliance).
Patients on antidepressants should be monitored carefully for
side effects or adverse drug reactions (listed under Side Effects and
Adverse Drug Reactions). Generally, antidepressant therapy of a
first episode of unipolar depression should continue for 6 months.
Patients with recurrent or chronic depression require longer or
perhaps lifelong maintenance treatment. Increasing the dose,
augmentation with lithium or triiodothyronine (liothyronine sodium
[Cytomel]) or a psychostimulant (e.g., methylphenidate), switching
antidepressants, or addition of a second antidepressant is helpful in
treating refractory depression. Patients on most TCAs require
serum level measurements to determine appropriate dosing.
All patients, but especially children and adolescents, should be
carefully monitored for increased suicidal thinking associated with
antidepressant medication treatment. Although antidepressants may
reduce the overall suicide rate by treating underlying depression,
they may also transiently increase suicidality during periods of
initiation or cessation of treatment as well as during dosage
adjustments.
SIDE EFFECTS AND ADVERSE DRUG

REACTIONS
SELECTIVE SEROTONIN REUPTAKE INHIBITORS

Although specific SSRIs have slightly different side-effect profiles,
as a group, their main side effects are nausea, headache,
neuromuscular restlessness (resembling akathisia), insomnia or
sedation, and delayed ejaculation/anorgasmia. SSRIs combined
with MAOIs are dangerous: a fatal serotonin syndrome may result.
TRICYCLIC ANTIDEPRESSANTS
TCAs in many patients are quite well tolerated; but because of their
side effects, TCAs are less well tolerated overall than are SSRIs,
bupropion, or venlafaxine. The major side effects associated with
TCAs are orthostatic hypotension, anticholinergic effects, cardiac
toxicity, and sexual dysfunction. Specific TCAs have relative
degrees of each of these effects.
Orthostatic hypotension is the most common serious side effect
of the TCAs. This is particularly worrisome in elderly patients,
who may be more prone to falls. Anticholinergic toxicity can be
mild, including dry mouth, constipation, blurred near vision, and
urinary hesitancy, or more severe, with agitation, motor
restlessness, hallucinations, delirium, and seizures.
Cardiac toxicity may limit the use of TCAs in some patients.
TCAs have quinidine-like effects on the heart, potentially causing
sinus tachycardia; supraventricular tachyarrhythmias; ventricular
tachycardia; ventricular fibrillation; prolongation of PR, QRS, and
QT intervals; bundle branch block; first-, second-, and third-degree
heart block; or ST and T-wave changes. Major complications from
TCAs are rare in patients with a normal heart. TCAs should be
avoided in patients with conduction system disease and should be
used with extreme caution in patients who have overdosed on
medication or have been recurrently suicidal.
Sexual dysfunction includes impotence in men and decreased
sexual arousal in women.
MONOAMINE OXIDASE INHIBITORS

Patients who take traditional oral MAOIs are at risk for
hyperadrenergic crises from the ingestion of sympathomimetic
amines (such as tyramine) that fail to be detoxified because of
inhibition of the gastrointestinal monoamine oxidase system.
Improper diet can lead to severe hypertensive crises (tyramine
crisis) with potential myocardial infarction or stroke. Foods that
must be avoided include cured meats or fish, beer, red wine, all
cheese except cottage and cream cheeses, and overripe fruits. Many
over-the-counter cold and pain remedies must also be avoided.
Treatment of hypertensive crisis, if severe, may require emergency
medical attention.
The new selegiline patch carries the same risks as traditional
oral MAOIs when used at 9 mg daily or above. At 6 mg daily,
however, no dietary restrictions are required.
MAOIs cause a dose-related orthostatic hypotension:
tranylcypromine can cause insomnia and agitation; phenelzine can
cause daytime somnolence.
OTHER ANTIDEPRESSANTS
Venlafaxine (Effexor, Effexor XR) and duloxetine (Cymbalta) are
serotonin and noradrenergic reuptake inhibitors with a better side-
effect profile than TCAs or MAOIs. Nefazodone and trazodone
(Desyrel) are serotonin-modulating antidepressants. Trazodone is
prescribed rarely as a sole antidepressant, but is often prescribed as
an adjunct to an SSRI for sleep because it has strong sedative
properties (at higher doses, it serves as an antidepressant). In
addition to sedation, trazodone can, on rare occasions, induce
priapism (prolonged, painful penile erection) that can cause
permanent damage. Patients must be instructed to seek emergency
treatment should such an erection occur. Nefazodone is similar to
trazodone but is less sedating at therapeutic doses. It appears to
have a low rate of sexual dysfunction, but has been associated with
serious hepatic abnormalities.
Bupropion (Wellbutrin, Wellbutrin SR, Zyban) appears to work
by inhibiting the uptake of dopamine and norepinephrine.
Bupropion has a low incidence of sexual side effects. In addition to
its efficacy in treating major depression, bupropion has been shown
to be effective in smoking cessation (marketed as Zyban) and
attention-deficit disorder. Bupropion has a higher-than-average risk
of seizures compared with other antidepressants. The risk of
seizures is greatest above a daily dose of 450 mg or after a single
dose of greater than 150 mg of immediate-release bupropion.
Mirtazapine (Remeron) is classified as a modulator of
norepinephrine and serotonin with α-2 antagonism. Because it is
also a histamine antagonist, mirtazapine is sedating and increases
appetite at some dosages. Mirtazapine has a low incidence of
sexual dysfunction. Vortioxetine (Trintellix) increases release of
multiple monoamines and has a mix of reuptake, agonist, and
antagonist properties at serotonin and other receptors. Vilazodone
(Viibryd) works as a serotonin reuptake inhibitor and as a partial
agonist at the serotonin 1A receptor.
Ketamine, a dissociative anesthetic, and similar compounds are
emerging as a potential treatment for suicidal ideation and
depression. Ketamine has a range of actions, but is primarily an
antagonist at the glutamatergic N-methyl-d-aspartate receptor (Fig.
16-2).
FIGURE 16-2. There are three main types of glutamate receptors.
Ketamine has a range of actions, but is primarily an antagonist at the
glutamatergic N-methyl-d-aspartate receptor. (From Bear MF,
Connors BW, Paradiso MA. Neuroscience: Exploring the Brain, 4th
ed. Philadelphia, PA: Wolters Kluwer, 2015. Adapted from Sawchenko
PE. Toward a new neurobiology of energy balance, appetite, and
obesity: the anatomists weigh in. J Comp Neurol. 1998;402:435–441.)
SOMATIC THERAPIES
Although all psychotropic drugs are “somatic” in that they affect a
part of the body (the brain), there are a growing number of
treatments available that use electrical, magnetic, or photic
stimulation of the central nervous system to treat depression. These
methods are being studied particularly for treatment-resistant
depression (i.e., episodes that do not respond to several
medications serially or in combination). The best studied and most
well known of these treatments is ECT, colloquially known as
“shock” therapy. It is discussed last after newer, more experimental
therapies.
VAGUS NERVE STIMULATION

Vagus nerve stimulation (VNS) therapy is approved for treatment-
resistant major depression. Although the precise mechanisms of
action of VNS in influencing depression are unknown, it is
presumed that retrograde conduction of impulses from peripheral
stimulation of the nerve influence central nervous system function.
The efficacy of VNS is not well established.
DEEP BRAIN STIMULATION

Deep brain stimulation is an established treatment for Parkinson’s
disease but remains under investigation for treatment of refractory
major depression. Large, randomized, controlled trials will be
needed to determine the technique’s true efficacy.
PHOTOTHERAPY
Phototherapy consists of the controlled administration of bright
light to treat specific psychiatric illnesses. Phototherapy is
administered using specially designed bright light boxes and has
been shown to be effective in the treatment of the seasonal subtype
of major depression (also known as seasonal affective disorder) and
in nonseasonal depression as well. Phototherapy is also used in the
treatment of the delayed sleep phase syndrome and jet lag. In the
treatment of seasonal affective disorder, early morning bright light
therapy is superior to evening light in most individuals. Light
intensity of 2,500 to 10,000 lux is most effective. Light therapy can
induce mania in susceptible individuals.
REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION

Repetitive transcranial magnetic stimulation (rTMS) is used for
patients who have not responded to antidepressant medications.
The rTMS method uses a strong magnetic field delivered by a head
coil to induce electrical activity in the underlying cerebral cortex
(Fig. 16-3). Although the procedure for rTMS is continually under
refinement, current evidence suggests that rTMS treatment for 5
days per week for 4 to 6 weeks at a frequency of 10 to 18 Hz to the
left prefrontal cortex is an effective approach.
FIGURE 16-3.Transcranial magnetic stimulation (TMS) uses magnetic
fields to induce electrical current in the underlying cortex and can be
targeted to brain regions that influence mood. (From Timby BK, Smith
NE. Introductory Medical-Surgical Nursing, 11th ed. Philadelphia, PA:
ELECTROCONVULSIVE THERAPY
ECT, formerly known as electric shock therapy, is one of the oldest
and most effective treatments for major depression. ECT also has
some efficacy in refractory mania and in psychoses with prominent
mood components or catatonia. ECT appears to work via the
induction of generalized seizure activity in the brain. The
peripheral manifestations of seizure activity are blocked by the use
of paralytics, and memory for the event is blocked by the use of
anesthetics and by seizure activity. Modern ECT has side effects of
short-term memory loss and confusion. Bilateral ECT is more
effective than unilateral ECT, but produces more cognitive side
effects.
KEY POINTS
Antidepressants have multiple indications
including various forms of depression, anxiety
disorders, bulimia, and OCD, among others.
Antidepressants act mainly on serotonergic and
noradrenergic receptor systems.
Some antidepressants have been shown to be
efficacious for particular disorders; for major
depression, all approved antidepressants reduce
symptoms to a similar degree. Antidepressants for
depression are often chosen on the basis of side-
effect profile and symptom constellation.
Some antidepressants, particularly TCAs, require
monitoring of serum levels.
The effects of antidepressants can be augmented
by the addition of lithium, thyroid hormone,
atypical antipsychotics or psychostimulants.
Antidepressants have side effects that vary
according to class.
VNS and rTMS are used for treatment-refractory
depression, but efficacy is not well established.
CLINICAL VIGNETTES
VIGNETTE 1
You evaluate a 47-year-old woman in the psychiatric assessment
service in a free-standing psychiatric hospital. She was brought in by
her husband because she had been acting funny. On further
questioning, the husband states that she has seemed a bit more
depressed lately but an hour or so ago, she began to seem slowed
down a bit, sedated, and a bit confused about the date and their plans
for the evening. He reports that the patient has a history of
depression, fibromyalgia, and hypertension. Her medications consist
of sertraline (150 mg PO daily), amitriptyline (50 mg PO at bedtime),
and irbesartan (300 mg PO daily). You interview the patient and ask
her what is wrong. You note that the patient seems a bit sleepy. Her
speech is notable for being somewhat slow and she makes an
occasional smacking sound when she speaks. She says that there is
nothing wrong, that she is feeling fine. She states that her mood is
good but her affect is flat. She denies auditory or visual hallucinations
or paranoia. She denies suicidal and homicidal ideation. When tested
for orientation, she is oriented only to person and place but is a bit
mixed up about the date, getting the wrong day of the week, month,
and year. On physical exam, the patient’s vital signs are heart rate
120 beats per minute; blood pressure 90/70 mm Hg; and temperature
101°F. Her pupils are somewhat dilated. Skin is flushed. The rest of
the physical exam is notable only for absent bowel signs.
1. The next essential step in this patient’s management is:

a. Have her meet with a crisis assessment specialist to complete
an intake for outpatient psychotherapy.
b. Obtain a urine drug screen to rule out substance use.
c. Discharge her home because she is not depressed or suicidal.
d. Call 911 to have the patient transported by an advanced
cardiac life support–equipped ambulance to the nearest
medical emergency room.
2. The patient is successfully transferred to the medical emergency

room. Her electrocardiogram is notable for a prolonged QRS
duration (>100 ms), among other abnormalities. A tricyclic blood
level is found to be in the toxic range. The patient is transferred to
the medical intensive care unit. She subsequently has an episode
of cardiac arrhythmia requiring defibrillation and resuscitation.
The most likely arrhythmia the patient experienced is:
a. Sinus tachycardia
b. Sinus bradycardia
c. Ventricular fibrillation/ventricular tachycardia
d. Atrial fibrillation
VIGNETTE 2
A 45-year-old man presents 3 months after a myocardial infarction he
sustained at his place of employment, where he works as the head
chef. For the past month, he has been having trouble concentrating
and remembering his recipes. He complains of decreased interest and
pleasure in his work and hobbies. He also has difficulty falling asleep
at night. He has had very little energy despite successful cardiac
rehabilitation. He has lost 20 lb during this time. The symptoms are
threatening his job and his relationship with his wife.
1. The most appropriate agent for initial treatment of this condition

would be:
a. Electroconvulsive therapy (ECT)
b. Tricyclic antidepressant
c. Lithium
d. Monoamine oxidase inhibitor (MAOI)
e. Selective serotonin reuptake inhibitor (SSRI)
2. The principal mechanism of action of Selective serotonin

reuptake inhibitor (SSRI) antidepressants is:
a. Agonist activity at postsynaptic serotonin receptors
b. Direct agonist activity at postsynaptic serotonin receptors
c. Binding to and blocking the presynaptic serotonin reuptake
transporter
d. Inhibition of monoamine oxidase
e. Serving as an α-2 presynaptic receptor antagonist
VIGNETTE 3
A patient with treatment-refractory depression has received ECT.
1. Which of the following is true of this treatment?

a. Bilateral ECT has fewer side effects than unilateral.
b. Bilateral ECT is more effective than unilateral.
c. ECT is indicated only for refractory depression.
d. The most common side effect is seizures.
e. ECT is contraindicated in psychosis.
ANSWERS
1. Answer D:
This patient is prescribed amitriptyline, a tricyclic antidepressant, and
is displaying classic signs of tricyclic overdose. Signs of tricyclic
overdose include confusion, delirium, and sometimes hallucinosis.
The anticholinergic properties of the tricyclic account for the smacking
sounds when speaking (due to reduced salivation and dry mouth),
tachycardia, flushing, pupillary dilation, and reduced bowel sounds.
Hypotension is also a sign of tricyclic overdose. Although she denies
suicidal ideation, it is not uncommon for individuals who intend suicide
to deny suicidal ideation to family/friends and treatment providers.
This patient has most likely taken an overdose of her prescribed
medications. Although the observable signs are consistent with
tricyclic overdose, it is not uncommon for patients to overdose on
multiple medications, and so a thorough evaluation will be essential.
The patient may need a crisis assessment at some point to plan for
therapy but given the life-threatening nature of tricyclic overdose, it is
not appropriate at the present time. A urine drug screen to rule out
substance use would be helpful, but given the concern for tricyclic
overdose, it is not appropriate to gather this information. It would be
inappropriate to discharge the patient home as the overdose could
well be fatal.
2. Answer C:
Tricyclic antidepressants inhibit rapid sodium channels, similar to
those of Class 1A antiarrhythmic medications, and can produce
dangerous arrhythmias. Ventricular arrhythmias are among the most
serious complications of tricyclic antidepressant overdose and may
prove fatal. Other major complications are severe hypotension and
seizures. Admission to an intensive care setting with cardiac
monitoring is essential in management of overdose. Sinus tachycardia
is common but would not require defibrillation. Sinus bradycardia is
not likely in tricyclic overdose as tachycardia is prominent. Atrial
fibrillation sometimes requires defibrillation but is not a common
complication of tricyclic overdose.
1. Answer E:
SSRI. The patient’s symptoms are consistent with major depression.
SSRIs are a first-line choice for the treatment of depression, but
sexual side effects are common and could potentially further
complicate his relationship with his wife. Tricyclic antidepressants are
very effective but are generally considered second-line
antidepressants because of their toxicity and side-effect profiles.
Lithium is primarily an augmentative treatment for depression.
Although very effective, MAOIs are not used as first-line
antidepressant treatments because of their requirement for dietary
restrictions. The dietary limitations of MAOIs would additionally limit
their usefulness in a patient who works as a chef. ECT is not
contraindicated 3 months after myocardial infarction, but it is indicated
only for severe or refractory depression.
2. Answer C:
The principle mechanism of action of SSRI antidepressants is
blockade of the presynaptic serotonin reuptake transporter. Acutely,
this action leads to increases in synaptic serotonin concentration.
SSRIs are thought to work in part by eventually increasing brain-
derived neurotrophic factor (BDNF). Direct agonist activity at
postsynaptic serotonin receptors are in part the mechanism of action
for buspirone, trazodone, nefazodone, vortioxetine, and vilazodone.
Inhibition of monoamine oxidase is the principle mechanism of action
of the MAOIs. α-2 Presynaptic antagonism is one of the mechanisms
of action of mirtazapine, which leads to increased serotonin and
norepinephrine release.
1. Answer B:
Bilateral ECT is more effective than unilateral. ECT has established
efficacy in depression, refractory mania, psychoses with prominent
mood components, and catatonia. ECT appears to work via the
induction of generalized seizure activity in the brain and, similar to
SSRI antidepressants, has been demonstrated to increase levels of
BDNF. The peripheral manifestations of seizure activity are blocked by
the use of paralytics, and memory for the event is blocked by the use
of anesthetics and by seizure activity. Modern ECT has side effects of
short-term memory loss and confusion. The most common side effect
of ECT is short-term memory loss and confusion. Bilateral ECT is
more effective than unilateral ECT but produces more cognitive side
effects.
INTRODUCTION
Mood stabilizers are psychotropic medications that promote
euthymia (a normal, nondepressed, reasonably positive mood) in
bipolar disorder. They generally treat and prevent the recurrence of
elevated (manic) or depressed moods. The term mood stabilizers
traditionally refers to lithium, valproate, carbamazepine,
oxcarbazepine, and lamotrigine. More recently, it has been proved
that some atypical antipsychotics have mood-stabilizing properties,
meaning that they are able to treat and prevent the recurrence of
manic or depressed phases of bipolar disorder. This capacity was
discussed in Chapter 15. Table 17-1 lists the traditional mood
stabilizers, their dosages, and therapeutic levels.
TABLE 17-1. Common Mood Stabilizers

Drugs Starting Therapeutic Therapeutic Serum
Dosage Dosage (mg/day) Concentration
Lithium 300 mg 900–2,400 0.6–1.2 mEq/L
carbonate bid–tid
Valproic acid 250 mg 750–3,000 50–125 mg/L
bid–tid
Lamotrigine 25 mg qd 200–400 —
Carbamazepine 100 mg 600–1,800 4–12 mg/L
bid–tid
Oxcarbazepine 150 mg 600–1,200 —
bid
Dosages are generally lower for geriatric patients, patients taking medications inhibiting metabolism
of the drug, or patients with other medical problems.
INDICATIONS
Mood stabilizers are indicated acutely (in conjunction with
antipsychotics) for the treatment of mania. They are indicated for
long-term maintenance prophylaxis against depression and mania
in individuals with bipolar disorder. Anticonvulsant medications
(valproate, lamotrigine, carbamazepine, and oxcarbazepine) may be
useful in individuals experiencing mood instability. Mood
stabilizers are also used for treatment of impulsive behavior in
individuals without bipolar disorder.
The choice of mood stabilizer is based on a patient’s particular
psychiatric illness (i.e., subtype of bipolar disorder) and other
clinical factors such as side effects, metabolic routes, patient
tolerance, and a history of patient or first-degree relative drug
responsiveness. Table 17-2 lists the major mood stabilizers and
their most common indications. Some common and more serious
side effects of mood stabilizers are listed in Table 17-3.
TABLE 17-2. Psychiatric Indications for Mood Stabilizers

Drug Uses
Lithium Acute mania
Bipolar depression
Long-term maintenance in bipolar disorder
Augmentation of antidepressant medications
Impulse dyscontrol
Valproate Acute mania
Impulse dyscontrol
Carbamazepine Acute mania
Impulse dyscontrol
May be more effective in rapid-cycling or mixed bipolar
disorder
Lamotrigine Bipolar depression
Some indications are Food and Drug Administration approved; others are based on clinical
experience and evidence.
TABLE 17-3. Drugs Used as Mood Stabilizers

Drug Side-Effect Profile
Lithium Therapeutic levels
CNS Sedation, cognitive clouding, fine
tremor
Endocrine Abnormal TSH, clinical
hypothyroidism
Cardiac T-wave change, sinus arrhythmia
Renal Polyuria
Dermatologic Acne, psoriasis
Gastrointestinal Nausea, vomiting, diarrhea
Hematologic Benign leukocytosis
Other Weight gain, fluid retention
Toxic levels
CNS Ataxia, coarse tremor, confusion,
seizure, coma, death
Cardiac Sinus arrest
Valproate Therapeutic levels
CNS Somnolence, ataxia, tremor
Endocrine Menstrual irregularities, thyroid
abnormalities
Dermatologic Alopecia, rash
Hepatic Mild transaminitis
Gastrointestinal Nausea, vomiting, indigestion
Hematologic Thrombocytopenia, platelet
dysfunction
Other Edema, polycystic ovarian syndrome
Toxic levels
CNS Ataxia, confusion, coma, death
Cardiac Cardiac arrest
Idiosyncratic
Hepatic Fatal hepatotoxicity
Gastrointestinal Pancreatitis
Hematologic Agranulocytosis
Carbamazepine Therapeutic levels
CNS Ataxia, sedation, dizziness, diplopia
Dermatologic Rash
Cardiac Decreased atrioventricular conduction
Hematologic Benign leukopenia
Gastrointestinal Nausea
Toxic levels
CNS Somnolence, autonomic instability,
coma, death
Cardiac Atrioventricular block
Respiratory Respiratory depression
Idiosyncratic
Hematologic Agranulocytosis, pancytopenia,
aplastic anemia
Lamotrigine Therapeutic levels
CNS Dizziness, anxiety, insomnia,
somnolence, coordination
abnormality, headache
Endocrine Dysmenorrhea
Cardiac Chest pain
Dermatologic Rash, serious life-threatening rash
(Stevens-Johnson’s)
Gastrointestinal Nausea, vomiting, dyspepsia
Other Weight decrease, infection, rhinitis
Toxic levels
CNS Ataxia, nystagmus, seizures, coma,
death
Cardiac Intraventricular conduction delay
CNS, central nervous system; TSH, thyroid-stimulating hormone.
The mechanism of action of mood stabilizers in bipolar illness

is unclear. The range of neurotransmitters affected by these
medications and their disparate modes of action suggest that mania
may be controlled by altering the function of several different
neurotransmitter systems. Conversely, they may share a common
mechanism of action that is yet to be elucidated.
LITHIUM
MECHANISM OF ACTION
Lithium’s mechanism of action in the treatment of mania is not
well determined. Lithium alters at least two intracellular second
messenger systems—the adenyl cyclase, cyclic adenosine
monophosphate system, and the G protein–coupled
phosphoinositide systems—and, as an ion, can directly alter ion
channel function. Because norepinephrine and serotonin in the
central nervous system (CNS) use G protein–coupled receptors as
one of their mechanisms of action, their function is altered by
lithium. Lithium also alters γ-aminobutyric acid (GABA)
metabolism. It also has neuroprotective effects through
enhancement of brain-derived neurotrophic factor (BDNF).
Lithium is indicated as a first-line treatment for bipolar disorder in
individuals with normal renal function. Lithium is also used to
augment other antidepressants in unipolar depression. Lithium is
renally cleared and can easily reach toxic levels in persons with
altered renal function (e.g., especially elderly individuals) or in
persons who are dehydrated. It may be less effective in the
treatment of the rapid-cycling variant of bipolar disorder. When
used in the treatment of bipolar disorder, lithium has been shown to
reduce the incidence of completed suicide. Of note, when patients
need discontinuation of lithium therapy, slow taper of lithium is
associated with a loss of lithium’s therapeutic effect in reducing
suicide; however, abrupt lithium taper is not only associated with
loss of the effect on reducing suicide but also associated with a 10-
fold or more increase in suicide that persists for at least 1 year.
Therefore, whenever possible, lithium should be tapered slowly
according to guidelines in the literature.
Successful lithium therapy requires that the patient take daily
dosages of the drug consistently. The therapeutic effect generally
occurs after 2 to 4 weeks of consistent use. Serum levels should be
monitored weekly until a stable dosing regimen has been obtained,
upon which twice-yearly monitoring is sufficient. Dosage is
generally titrated to a level of 0.6 to 1.2 mEq/L (mmol/L), and
levels should be obtained 12 hours after a dose is taken. Additional
monitoring is necessary in a patient with variable compliance or
altered renal function. In addition, patients should be warned about
toxicity and should be regularly assessed for side effects. Lithium
has a narrow therapeutic window, and patients can develop toxicity
at prescribed doses, especially if they undergo an abrupt change in
renal function. Serum thyroid-stimulating hormone (TSH) and
creatinine levels should also be checked at regular intervals.
SIDE EFFECTS
Common side effects of lithium therapy include tremor, polyuria,
excessive thirst, gastrointestinal distress, minor memory problems,
acne exacerbation, and weight gain. At toxic levels (usually >2
mmol/L), ataxia, coarse tremor, diarrhea, confusion, coma, sinus
arrest, and death can occur. Tremor can occur in up to 50% of
patients but low-dose β-blockers such as propranolol can be
effective. Polyuria and polydipsia occur in approximately 70% of
patients, whereas transiently elevated TSH can occur in up to 30%
of patients.
VALPROATE
MECHANISM OF ACTION
Valproate’s mechanism of action is thought to be due in part to
augmentation of GABA function in the CNS. Valproate increases
GABA synthesis, decreases GABA breakdown, and enhances its
postsynaptic efficacy. It also likely has neuroprotective effects
through enhancement of BDNF.
Valproate is indicated for the treatment of acute mania and is
widely used in the maintenance phase of bipolar I disorder (see
Table 17-2). It is effective for the rapid-cycling and mixed variants
of bipolar disorder. It may not provide prophylaxis against
depression in bipolar disorder or augment antidepressants. It was
developed as an anticonvulsant and thus is used to treat seizure
disorders. It also has efficacy in treating migraine headaches and is
used off-label in treating general impulse dyscontrol.
In otherwise physically healthy adults, valproate can be initiated at
a larger-than-usual dosage (20 to 25 mg/kg body weight) for the
acute treatment of a manic episode, known as loading. In the acute
hospital setting, this allows for rapid achievement of a therapeutic
blood level. A lower average daily oral dosage is then started the
day after loading. Rapid (less than 7 days) decreases in manic
symptoms can be achieved with this method. The full effect of the
medicine is generally not seen until 2 to 4 weeks of consistent daily
dosing at a therapeutic level. Serum levels should be monitored
regularly until a stable blood level and dosing regimen have been
obtained. Valproate has a wide therapeutic dosing index of 50 to
125 μg/L. Liver function tests should be checked at baseline and
frequently during the first 6 months, especially because the
idiosyncratic reaction of fatal hepatotoxicity is most frequent in this
time frame.
SIDE EFFECTS
At therapeutic levels, valproate produces a variety of side effects,
including sedation, mild tremor, mild ataxia, and gastrointestinal
distress. Weight gain can occur in up to 50% of people. Polycystic
ovarian syndrome due to increased androgen production can also
occur along with thrombocytopenia and impaired platelet function.
At toxic levels, confusion, coma, cardiac arrest, and death can
occur. Valproate usage carries with it the risk of idiosyncratic but
serious side effects. These include fatal hepatotoxicity, fulminant
pancreatitis, and agranulocytosis.
LAMOTRIGINE
MECHANISM OF ACTION
The mechanism of action of lamotrigine in bipolar disorder is
unknown. Lamotrigine is approved by the U.S. Food and Drug
Administration (FDA) for use in the maintenance and depressed
phases of bipolar I disorder. Lamotrigine in vitro has been shown
to inhibit voltage-sensitive sodium channels. This effect is believed
to stabilize neuronal membranes and modulate presynaptic
excitatory glutamate release.
Although studies are still ongoing regarding the use of lamotrigine
in bipolar disorder, it appears to be more effective in treating or
preventing the depressive phase of bipolar I disorder than the
manic phase.
Dosages are started low (25 mg daily for the first 2 weeks) and
increased slowly to the average therapeutic dosage of 200 mg daily.
Dosages are generally lowered for elderly individuals, those with
renal or other organ impairment, or when combined with
interacting agents (i.e., valproic acid). If lamotrigine therapy is
interrupted for more than 5 half-lives, it should be restarted at the
initial dose.
The therapeutic effect of lamotrigine is delayed by the need to
gradually increase the dosage to a therapeutic level. The benefits
are usually seen when dosage exceeds 150 mg for 2 to 4 weeks.
The development of serious allergic reactions (rash leading to
Stevens-Johnson’s syndrome) to lamotrigine appears to be related
to rapid-dose escalation or drug interactions. A clinically useful
assay for serum levels of lamotrigine is not available. Generally,
this medication should only be prescribed by a qualified
psychiatrist, neurologist, or other provider who is aware of the
complex drug interactions that exist particularly between valproic
acid and lamotrigine.
SIDE EFFECTS
Lamotrigine can commonly cause ataxia, blurred vision, diplopia,
dizziness, nausea, and vomiting. Severe, potentially life-threatening
allergic rashes have been reported with the use of lamotrigine. The
allergic reaction can begin as a simple rash (10%) and lead to
Stevens-Johnson’s syndrome (1%). The rate of serious or life-
threatening rashes is greater in the pediatric age group.
CARBAMAZEPINE
MECHANISM OF ACTION
The mechanism of action of carbamazepine in bipolar illness is
unknown. Carbamazepine blocks sodium channels in neurons that
have just produced an action potential, blocking the neuron from
repetitive firing. In addition, carbamazepine decreases the amount
of transmitter release at presynaptic terminals. Carbamazepine also
appears to indirectly alter central GABA receptors.
Carbamazepine is generally considered to be a second-line drug
(after lithium and valproate) for the treatment of mania (see Table
17-2). The extended release formulation of carbamazepine has
received FDA approval for the treatment of bipolar disorder. It is
used in acute mania, prophylaxis against mania in bipolar disorder,
and may be more effective than lithium in rapid-cycling and mixed
mania. Carbamazepine’s efficacy in the prophylaxis and treatment
of depression is not clear. It is also used off-label in treating
impulse dyscontrol. Carbamazepine can be used alone or in
combination with lithium or an antipsychotic agent.
The therapeutic effects of carbamazepine are seen from 2 to 4
weeks after consistent, daily dosing. Carbamazepine levels (4 to 12
μg/mL) should be monitored regularly until a stable dosing
regimen has been obtained. Carbamazepine also may autoinduce its
own metabolism, so the dosage may need to be increased
approximately 1 month after initiation. Patients should be carefully
monitored for rash, signs of toxicity, or evidence of severe bone
marrow suppression.
SIDE EFFECTS
Carbamazepine, at therapeutic levels, produces CNS side effects
similar to those of lithium and valproate. Nausea, rash, and mild
leukopenia are also common. Carbamazepine has an antidiuretic
effect and can cause hyponatremia. At toxic levels, autonomic
instability, atrioventricular block, respiratory depression, and coma
can occur. Carbamazepine has idiosyncratic side effects of
agranulocytosis, pancytopenia, and aplastic anemia.
OXCARBAZEPINE
Oxcarbazepine is an anticonvulsant that is structurally similar to
carbamazepine but one that has fewer side effects and drug
interactions. The efficacy of oxcarbazepine in treating the various
stages of bipolar disorder has not been well proved, but, a few
small, controlled studies suggest that oxcarbazepine is effective in
acute mania. Other studies suggest that the drug may also be
effective in the maintenance phase of bipolar disorder.
ANTIPSYCHOTIC MEDICATIONS AND

BIPOLAR DISORDER
Several atypical antipsychotic medications (Chapter 15) are also
approved for use in bipolar disorder. Atypical antipsychotics
approved for the mood component of bipolar disorder include
aripiprazole, olanzapine, olanzapine/fluoxetine combination,
quetiapine, risperidone, and ziprasidone. Lurasidone is approved
for depressive episodes in bipolar disorder. They can be used as
monotherapy or in conjunction with a traditional mood stabilizer to
achieve more optimal mood stability.
KEY POINTS
Mood stabilizers are indicated for the treatment of
all episodes of bipolar disorder.
Mood stabilizers work by unknown but likely varied
mechanisms.
Effective treatment is achieved through daily
dosing at a therapeutic blood level.
Mood stabilizers have serious toxicities, so
patients require regular monitoring.
Some atypical antipsychotics also have mood-
stabilizing properties and can be used as
monotherapy or in conjunction with more
traditional mood stabilizers.
CLINICAL VIGNETTES
VIGNETTE 1
A 27-year-old female patient presents to the emergency department
complaining of the recent onset of tremor and diarrhea. On
examination, she is oriented to place and person but not to time and
exhibits impairment in short-term memory. Her gait is ataxic, and she
exhibits a coarse bilateral tremor. She reports that her outpatient
psychiatrist started her on a new medication for bipolar disorder 2
weeks ago, but she recently doubled the dose because it did not seem
to be working.
1. This medication is most likely to be:

a. Haloperidol
b. Lamotrigine
c. Lithium
d. Carbamazepine
e. Valproic acid
2. What are potential mechanisms of action for lithium?

a. Augmentation of γ-aminobutyric acid (GABA) function and
enhancing brain-derived neurotrophic factor (BDNF)
b. Blockade of recently active sodium channels
c. Blockade of voltage-sensitive sodium channels
d. Alteration of adenyl cyclase/cyclic adenosine monophosphate
(AMP) and phosphoinositide systems
VIGNETTE 2
A 22-year-old man presents to your office pacing and speaking
rapidly. Your nurse tries to get him to calm down and wait for you but
is unable. She asks you to see him immediately. When you enter the
room, he jumps up and starts rambling about going to medical school
and being especially gifted. He describes no longer needing sleep,
mastering speed reading, and spending money on expensive clothes
for his new career. He asks you what he should wear when he wins
the Nobel Prize for medicine. After gathering more history from his
family, you decide that he is acutely manic.
1. The medication most likely to help his condition is:

a. Flumazenil
b. Fluoxetine
c. Acamprosate
d. Gabapentin
e. Valproic acid
VIGNETTE 3
A college student presents with symptoms of major depression. She
states that she was doing very well up until 1 week previously. In fact,
she states that she had not needed any sleep, her creativity was at an
all-time high, and she was unbelievably productive in her work. She
reports that she was uncharacteristically promiscuous and states that
this behavior was followed by a period of irritability, difficulty
concentrating, and a persistent inability to sleep. These issues were
followed by the current depressive episode.
1. Which of the following therapeutic agents would be most

appropriate?
a. Venlafaxine
b. Mirtazapine
c. Lurasidone
d. Electroconvulsive therapy (ECT)
e. Valium (diazepam)
ANSWERS
1. Answer C:
Side effects of lithium at a normal dose include tremor, gastrointestinal
problems such as diarrhea, and minor cognitive impairment. At toxic
doses, lithium causes a coarse tremor, confusion, and ataxia.
Because lithium has a narrow therapeutic window, this patient has
reached toxic serum levels as a result of doubling her dose. Lithium
toxicity can be life threatening because of risk of seizures, coma, and
arrhythmias. The mainstay of treatment for severe lithium intoxication
is hemodialysis depending on severity. Haloperidol may be associated
with acute extrapyramidal side effects and QTc prolongation on
electrocardiogram. Lamotrigine can cause severe life-threatening
rashes including Stevens–Johnson’s syndrome. Carbamazepine may
cause gastrointestinal distress, coma, agranulocytosis, and aplastic
anemia. Valproic acid is associated with gastrointestinal distress,
coma, transaminitis, and rarely fatal hepatotoxicity.
2. Answer D:
The precise mechanism of action of mood stabilizers is unknown.
Lithium alters at least two intracellular second messenger systems—
the adenyl cyclase, cyclic AMP system, and the G protein–coupled
phosphoinositide systems—and, as an ion, can directly alter ion
channel function. Because norepinephrine and serotonin in the central
nervous system (CNS) use G protein–coupled receptors as one of
their mechanisms of action, their function is altered by lithium. Lithium
also alters GABA metabolism. It also has neuroprotective effects
through enhancement of BDNF. Of other mood stabilizers, valproate’s
mechanism of action is thought to be due in part to augmentation of
GABA function in the CNS. Valproate increases GABA synthesis,
decreases GABA breakdown, and enhances its postsynaptic efficacy.
It also likely has neuroprotective effects through enhancement of
BDNF. Lamotrigine is approved by the FDA for use in the
maintenance and depressed phases of bipolar I disorder. Lamotrigine
in vitro has been shown to inhibit voltage-sensitive sodium channels.
This effect is believed to stabilize neuronal membranes and modulate
presynaptic excitatory glutamate release. Carbamazepine blocks
sodium channels in neurons that have just produced an action
potential, blocking the neuron from repetitive firing. In addition,
carbamazepine decreases the amount of transmitter release at
presynaptic terminals. Carbamazepine also appears to indirectly alter
central GABA receptors.
1. Answer E:
The patient shows classic symptoms of mania: rapid speech,
grandiosity, decreased need for sleep, and spending sprees. Of the
medicines listed, valproic acid, an anticonvulsant mood stabilizer,
would be the most helpful. Flumazenil, a benzodiazepine antagonist,
would not have any impact. Fluoxetine, a selective serotonin reuptake
inhibitor antidepressant, would not treat the mania and may, in fact,
worsen it. Acamprosate counteracts alcohol dependence but does not
improve mania. Gabapentin, although initially thought to have mood-
stabilizing properties, does not have clear effects in mania and would
be less effective than standard treatments such as valproic acid.
1. Answer C:
The patient described meets probable criteria for bipolar disorder and
is presenting in the depressed phase of her disorder. Lurasidone is an
atypical antipsychotic that is approved as monotherapy for bipolar
depression. The atypical antipsychotic medications as a class, in
addition to dopamine antagonism, have prominent serotonin 2a
receptor blockade. Lurasidone has additional actions as an antagonist
at the serotonin 7 receptor and partial against actions at the serotonin
1A receptor. The drug is additionally an antagonist at α-2 receptors,
although the contribution of these actions to therapeutic effects is
unknown. Benzodiazepines, such as diazepam, may be used also in
the management of acute mania but are not first-line treatments for
bipolar depression. The antidepressants venlafaxine and mirtazapine
should be used with caution in bipolar depression or used only in
conjunction with an atypical antipsychotic because of the possibility of
inducing mania or producing a more severe mania. ECT is useful in
refractory depression or mania, but we do not have evidence for
treatment-refractory bipolar disorder in this patient.
INTRODUCTION
The medications discussed in this chapter have anxiolysis in
common. Although benzodiazepines have a wide variety of clinical
applications (e.g., as preanesthetics, in the treatment of status
epilepticus, as muscle relaxants, and in the treatment of insomnia),
and other medications (e.g., antidepressants) are of utility in
treating some forms of anxiety, the benzodiazepines are uniquely
effective for the rapid relief of a broad spectrum of anxiety
symptoms. Buspirone is a novel medication that, at present, is used
primarily in the treatment of generalized anxiety disorder; it does
not appear to be effective in treating other types of anxiety (e.g.,
panic).
BENZODIAZEPINES
INDICATIONS
Benzodiazepines are among the most widely used drugs in all of
medicine. In psychiatry, they are used for immediate treatment of
acute problems due to their rapid effect. They can be used to treat a
variety of anxiety disorders: panic disorder, generalized anxiety
disorder, anxiety associated with stressful life events (as in
adjustment disorders with anxiety), and anxiety that complicates
depression (see Chapter 4). In addition, benzodiazepines are used
for the short-term treatment of insomnia; for the treatment of
alcohol withdrawal; in agitation associated with mania, dementia,
and psychotic disorders; and in the treatment of catatonia (Table
18-1).
TABLE 18-1. Psychiatric Uses for Benzodiazepines

Anxiety Disorders
Panic disorder
Social phobia
Mood Disorders
Depression-related anxiety
Depression-related insomnia
Agitation in manic episode
Adjustment Disorders
Treatment of adjustment disorder with anxiety
Sleep Disorders
Short-term treatment of insomnia
Miscellaneous
Treatment of akathisia induced by neuroleptics
Agitation from psychosis or other causes
Catatonia (especially lorazepam)
Alcohol withdrawal
MECHANISM OF ACTION
Benzodiazepines function as anxiolytics via their agonist action at
the central nervous system (CNS) γ-aminobutyric acid (GABA)
receptor. GABA is a widespread inhibitory neurotransmitter that is
synthesized from glutamate (Fig. 18-1), with three major receptor
types, A, B, and C. Benzodiazepines are agonists at GABA
receptor type A (which is also the target of barbiturates and
alcohol) (Fig. 18-2). Each GABA-A receptor is ionotropic and
forms a ligand-gated ion channel that is permeable to chloride.
Because benzodiazepines are direct agonists at a rapidly
responding ion channel, their mechanism of action is virtually
instantaneous with their arrival in the CNS (in contrast to
buspirone; information to follow).
FIGURE 18-1. γ-Aminobutyric acid (GABA) synthesis. GABA is

synthesized from glutamate by the actions of glutamate (glutamic
acid) decarboxylase (GAD). (From Bear MF, Connors BW, Paradiso
MA. Neuroscience: Exploring the Brain, 4th ed. Philadelphia, PA:
FIGURE 18-2. The action of benzodiazepines. Benzodiazepines bind
to a site on the γ-aminobutyric acid (GABA)-A receptor that makes it
much more responsive to GABA, the major inhibitory neurotransmitter
in the forebrain. In the presence of GABA, benzodiazepines increase
the frequency of opening of the chloride (Cl−) channel. Barbiturates, in
turn, prolong the duration of channel opening in the presence of
GABA. (From Bear MF, Connors BW, Paradiso MA. Neuroscience:
Exploring the Brain, 4th ed. Philadelphia, PA: Wolters Kluwer, 2015.)
Emerging evidence in anxiety disorders suggests that altered

GABA function is associated with anxiety. For example, there is
evidence for reduced numbers of GABA receptors in the CNS of
patients with some anxiety disorders (Fig. 18-3). In addition to this
reduced density of GABA receptors in anxiety, the remaining
GABA receptors may show decreased or altered responsiveness to
benzodiazepines. There may also be reductions in the concentration
of GABA in the cortex of this group; however, GABA is clearly
not the only neurotransmitter implicated in susceptibility to anxiety
disorders. Medications that alter monoamine function, such as
serotonin and norepinephrine reuptake inhibitors, as well as
buspirone (see later) are also highly effective in treating some
anxiety disorders.
FIGURE 18-3. Reduced frontal lobe γ-aminobutyric acid (GABA)-A

receptor density in panic disorder. Left is control; right is patient with
panic disorder. GABA-A receptor density as measured by a
radioactive benzodiazepine-PET ligand that binds the GABA receptor
reveals decreased receptor binding in the frontal lobe in panic
disorder. The hottest color (red) indicates the highest level of receptor
binding and cooler colors indicate lower receptor binding. Brain slices
are axial/horizontal sections; frontal lobe is at the top of the figure.
(From Nutt DJ, Malizia AL. New insights into the role of the GABAA-
benzodiazepine receptor in psychiatric disorder. Br J Psychiatry.
2001;179:390–396. Reproduced with permission.)
The selection of a benzodiazepine should be based on an
understanding of potency, rate of onset, route of metabolism,
effective half-life, and clinically proven effectiveness. Although all
benzodiazepines appear to function by common mechanisms, the
particular combination of the previously mentioned factors (and
perhaps yet unknown variations in affinity for receptor subtypes)
produces varied clinical indications for different benzodiazepines.
Table 18-2 illustrates the properties of some commonly used
benzodiazepines and their common clinical uses.
Potency
The high-potency benzodiazepines alprazolam and clonazepam are
used in the treatment of panic disorder.
Rate of Onset
Fast-onset benzodiazepines, such as diazepam, may produce a
“high” feeling and are potentially more addictive. The fast-onset
benzodiazepines flurazepam and triazolam are commonly used for,
and have an indication for, insomnia. However, given that
insomnia can be a symptom of another disorder, benzodiazepines
should not be used for more than 7 to 10 days consecutively for this
indication because dependence can develop and a thorough workup
of insomnia should occur.
Route of Metabolism
All benzodiazepines listed, with the exception of lorazepam,
oxazepam, and temazepam, require oxidation as a step in their
metabolism. Because the oxidative functions of the liver are
impaired with liver disease (e.g., cirrhosis) or with a general
decline in liver function (e.g., aging), benzodiazepines that require
oxidation are more likely to accumulate to toxic levels in
individuals with impaired liver function.
Elimination Half-life
The elimination half-life depicts the effective duration of action of
the metabolized medications. For medications with long
elimination half-lives, toxicity can easily occur with repetitive
dosing. In addition, toxicology screens may remain positive for
several days after the last dose of a long-acting benzodiazepine.
Drugs with longer elimination half-lives offer less likelihood of
interdose symptom rebound. For example, clonazepam is now
favored over alprazolam in the treatment of panic because its
longer elimination half-life provides better interdose control of
panic symptoms. Medications with shorter elimination half-lives
are useful for conditions such as insomnia because they are less
likely to produce residual daytime sedation or grogginess.
Active Metabolites
Medications with active metabolites generally have a longer
elimination half-life. Among the benzodiazepines, all but the three
drugs metabolized by conjugation (lorazepam, oxazepam,
temazepam) and clonazepam have active metabolites.
Benzodiazepine dosing is generally titrated to maximize symptom
relief while minimizing side effects and the potential for abuse. No
routine monitoring is required; although serum drug levels can be
obtained, they are not of great clinical use. Care must be taken in
prescribing benzodiazepines because of their ability to cause
physiologic dependence. They cannot be discontinued abruptly
because of the risk of a withdrawal syndrome that may include
seizures. Tolerance and dependence can emerge even after several
weeks of use. Use in the elderly must be performed with extreme
caution, because benzodiazepines have been shown to increase the
risk of falls resulting in large bone fractures. Long-acting
benzodiazepines in the elderly have also been associated with
higher rates of motor vehicle accidents.

The major side effects of benzodiazepines are related to the CNS.
The primary side effect of benzodiazepines is sleepiness or a
general groggy feeling which occurs in about 10% of all persons
taking these medications. Although benzodiazepines are often used
to treat agitation, they may produce disinhibition (and therefore
worsen agitation) in some patients (i.e., in the elderly and children
in particular). Benzodiazepines are minimally depressive to the
respiratory system in healthy individuals, but can lead to fatal
carbon dioxide retention in patients with chronic obstructive
pulmonary disease. Long-term use of benzodiazepines is associated
with cognitive impairment that may not completely resolve after
discontinuation (this is still under active study). In healthy
individuals, death after overdose on benzodiazepines alone is rare,
but does occur when benzodiazepines are taken with alcohol and
other CNS depressant medications. Benzodiazepines can also be
teratogenic and can result in “floppy baby syndrome,” so their use
in pregnancy is only advised under particular circumstances.
BUSPIRONE (BUSPAR)
INDICATIONS
Buspirone is used primarily for generalized anxiety disorder.
Because of its long lag time to therapeutic effect (2 to 4 weeks),
patients with severe anxiety symptoms may be unable to sustain a
clinical trial. Buspirone is favored as a treatment in individuals
with a history of substance abuse. In general, buspirone lacks the
reliability of benzodiazepines in relieving anxiety but can be
effective in some people. It does not have weight gain or sexual
side effects like some other medications.
MECHANISM OF ACTION
Buspirone is a novel medication that appears to act as an anxiolytic
via its action as a partial agonist at the serotonergic 5HT1A
receptor. In addition, it has some D2 agonist and antagonist effects,
although with unclear clinical significance. Unlike the
benzodiazepines, it does not work rapidly; a period of several
weeks of sustained dosing is required to obtain symptomatic relief.
Buspirone has no GABA receptor affinity and is therefore not
useful in treating benzodiazepine or alcohol withdrawal. It is not a
sedative and is not useful in treating insomnia.
No routine monitoring or drug levels are required when using
buspirone.

Buspirone does not tend to cause sedation, nor does it produce a
significant withdrawal syndrome or dependence. The major side
effects are dizziness, sleepiness, nervousness, and nausea.
KEY POINTS
Anxiolytics include benzodiazepines and
buspirone.
Benzodiazepines bind to GABA-A receptors and
have a comparatively rapid onset of action;
buspirone binds to serotonin receptors and takes
effect after weeks of daily usage.
Benzodiazepines have a wide variety of uses,
including anxiolysis, alcohol detoxification,
agitation, and insomnia.
Benzodiazepines can cause cognitive impairment
and also increase the risk of falls and motor
vehicle accidents in elderly users.
Benzodiazepines produce physiologic
dependence and may manifest a significant
withdrawal syndrome.
Buspirone does not cause physiologic
dependence.
CLINICAL VIGNETTES
VIGNETTE 1
A 58-year-old man is transferred to your psychiatric facility after
medical stabilization at an outside hospital. The laboratory studies
sent from the outside hospital do not indicate any gross abnormalities.
The patient gives you permission to speak with his adult daughter who
can provide information about the events leading up to the
hospitalization. The daughter reports that her father has diabetes,
heart problems, and “bad nerves.” She reports that he takes a lot of
medications but had to stop his “nerve medication” about a week ago
because his insurance would no longer pay for it. She cannot recall
the name of the medication. She reports that 3 to 4 days ago, he
began complaining of nausea, vomiting, sweating, and feeling weak.
Yesterday, she found him in his room unresponsive with jerking
movements of his arms and legs.
1. What was the most likely cause of this man’s generalized

seizure?
a. Acute stroke
b. Nonketotic hyperglycemia
c. Sedative-hypnotic withdrawal
d. Hyponatremia
e. Alcohol withdrawal
VIGNETTE 2
A 36-year-old male patient with a history of sedative-hypnotic
dependence is admitted to the ICU after being found down at home by
his mother with an empty bottle of alprazolam pills at his bedside. He
is sedated and intubated by the medical team for agitation and
respiratory depression. The following day, he is extubated, and you
are consulted urgently for assessment of agitation. On examination,
you find the patient pacing around his room swearing at the nursing
staff and threatening to leave the hospital. He fails to cooperate with
your efforts to interview him, but you note that he appears to be
diaphoretic and observe a coarse tremor in his forearms. Reviewing
his vital signs, you note that they were within normal limits until 2
hours ago, when the patient’s pulse increased to 120 beats per minute
and his blood pressure increased to 150/100.
1. Which of the following medications is the best choice in

management of this patient?
a. Buprenorphine
b. Clonidine
c. Methadone
d. Phenobarbital
e. Propranolol
ANSWERS
1. Answer C:
At this point, the primary diagnostic consideration is sedative-hypnotic
withdrawal. These drugs are widely used to treat anxiety disorders.
Benzodiazepine withdrawal can be a life-threatening condition.
Depending on the drugs’ half-life and the presence of long-acting
metabolites, patients may show delayed withdrawal after stopping
medications. Signs and symptoms of sedative-hypnotic withdrawal
include restlessness, anxiety, tremors, weakness, vomiting, sweating,
hyperreflexia, and seizures. Many patients who have mild dependence
on benzodiazepines can be managed by a slow taper of the drug in an
outpatient setting. Patients with a more serious dependence or with
multiple comorbid medical illnesses, however, require a protocol
withdrawal in an inpatient setting. Most acute seizures occur within 48
hours of ischemic stroke onset and would likely have been preceded
by signs of a stroke including dysarthria, paralysis, or altered level of
consciousness. Acute metabolic disturbances can precipitate seizures
in individuals of any age. Both hypoglycemia and nonketotic
hyperglycemia occurring in poorly controlled diabetes, as well as
hyponatremia, hypocalcemia, and uremic and hepatic encephalopathy
are all causes of acute symptomatic seizures. The normal laboratory
studies make these etiologies less likely, however. Alcohol withdrawal
produces signs and symptoms similar to those of sedative-hypnotic
withdrawal, but there is no evidence from the history to suggest that
the patient is alcohol dependent.
1. Answer D:
This patient has a history of sedative-hypnotic dependence for
alprazolam and is admitted with signs of acute intoxication including
altered mental state (agitation) and respiratory depression. After
intubation for 1 day, the patient exhibits acute agitation, tachycardia,
hypertension, diaphoresis, and tremor. These signs and symptoms
are consistent with acute withdrawal, which can be managed by
detoxification with phenobarbital (a long-acting barbiturate) or,
alternatively, by using a benzodiazepine with a long half-life.
Buprenorphine, a μ-opioid receptor partial agonist, and methadone, a
weak μ-opioid receptor agonist, are used in the treatment of opioid
dependence. Clonidine is an α-2 receptor agonist that treats the
autonomic symptoms of opioid withdrawal. Propranolol is a
nonselective β-adrenergic antagonist that is sometimes used in the
treatment of social phobia.
INTRODUCTION
This chapter includes medications that are used to treat substance
dependence, attention-deficit hyperactivity disorder (ADHD), and
Alzheimer’s disease (AD), as well as medicines commonly used in
psychiatric practice that do not fall into the conventional categories
of psychotherapeutic drugs. Many medications used in general
medical practice have side effects such as sedation, stimulation, or
anxiolysis. These side effects are often exploited in psychiatry to
target specific symptoms (e.g., insomnia, anergia). Other drugs,
such as psychostimulants, have precise indications for psychiatric
usage. Table 19-1 shows common indications of anticholinergics,
β-blockers, α-receptor agents, psychostimulants, thyroid hormones,
and other drugs. Many more medications than are discussed here
are included in the psychiatric armamentarium.
TABLE 19-1. Miscellaneous Medications Used in

Psychiatry
Medication Class Examples Common Psychiatric
Uses
Anticholinergics Benztropine, Neuroleptic-induced
trihexyphenidyl, Parkinsonism, acute
diphenhydramine dystonia, possibly akathisia
as third line
β-Blockers Propanolol Performance anxiety,
public speaking anxiety,
akathisia, aggression
α-Receptor Clonidine Autonomic arousal during
medications opiate withdrawal, ADHD,
Tourette’s syndrome,
impulsivity
Prazosin Nightmares associated with
posttraumatic stress
disorder
Guanfacine ADHD
Selective Atomoxetine ADHD, depression
norepinephrine
reuptake inhibitor
Psychostimulants Dextroamphetamine, ADHD, narcolepsy,
methylphenidate, excessive daytime
pemoline sleepiness, depression
μ-Opioid antagonist Naltrexone Alcohol use disorder,
opiate use disorder
Partial μ-opioid Buprenorphine Opiate use disorder
agonist
Opioid agonist Methadone Opiate use disorder
Glutamate Acamprosate Alcohol use disorder
modulator
Aldehyde Disulfiram Alcohol use disorder
dehydrogenase
inhibitor
Nicotinic partial Varenicline Smoking cessation
agonist
GABA modulators Zolpidem, zaleplon, Short-term treatment of
eszopiclone insomnia
Melatonin agonist Ramelteon Insomnia
Dopamine reuptake Modafinil, Narcolepsy
inhibitor armodafinil
GABA-B and GHB Sodium oxybate Narcolepsy
agonist
Acetylcholinesterase Donepezil, Enhancing cognition in
inhibitors rivastigmine, dementia
galantamine
N-Methyl-d- Memantine Enhancing cognition in
aspartate receptor dementia
antagonist
Ketone producer Caprylidene Metabolic processes in
Alzheimer disease
Thyroid hormone Levothyroxine Augmentation in
receptor agonists depression
ADHD, attention-deficit hyperactivity disorder; GABA, γ-aminobutyric acid; GHB, γ-
hydroxybutyrate; PTSD, posttraumatic stress disorder.
ANTICHOLINERGICS
Medications with anticholinergic activity are commonly used in
psychiatry to treat or provide prophylaxis for some types of
neuroleptic-induced movement disorders. Anticholinergics are
generally used as first-line agents in the treatment of neuroleptic-
induced Parkinsonism and for acute dystonia; they may also have
some utility in treating akathisia, but are best tried after β-blockers
and lorazepam. The most commonly used anticholinergics are
benztropine and trihexyphenidyl. In addition, diphenhydramine, an
antihistamine that also possesses anticholinergic properties, is
frequently used to treat neuroleptic-induced movement disorders
and to provide nonspecific sedation. These medications are central
nervous system (CNS) muscarinic antagonists. Side effects of
anticholinergics, caused by peripheral anticholinergic action,
include blurry vision (as a result of cycloplegia), constipation, and
urinary retention; their principal central side effects are sedation
and delirium. Anticholinergic toxicity is a major cause of delirium,
especially in individuals with dementia.
Β-BLOCKERS
β-Blockers are used widely in general medicine. In psychiatry, they
have a few specific uses. They are used off-label for performance
anxiety, public speaking anxiety, in the treatment of akathisia, and
for behavioral control in impulsive or aggressive patients. β-
Blockers likely alter behavior and mood states by altering both
central and peripheral catecholamine function. For example, in
anxiety, they may diminish central arousal; peripherally, they may
reduce tachycardia, tremor, sweating, and hyperventilation.
Common side effects of β-blockers include bradycardia,
hypotension, asthma exacerbation, and masked hypoglycemia in
diabetics. β-Blockers may also produce depression-like syndromes
characterized by fatigue and depressed mood.
Α-RECEPTOR MEDICATIONS
CLONIDINE
Clonidine is a CNS α-2 adrenoreceptor agonist. The α-2
adrenoreceptor is a presynaptic autoreceptor that inhibits the
release of CNS norepinephrine. The primary use of clonidine in
medicine is as an antihypertensive (Table 19-1). In psychiatry,
clonidine has been variously used. It is effective in decreasing
autonomic symptoms associated with opiate withdrawal, in the
treatment of ADHD and Tourette’s syndrome, and may be useful
for impulsiveness and other forms of behavioral dyscontrol. Side
effects include sedation, dizziness, and hypotension.
PRAZOSIN
Prazosin is a competitive α-1 antagonist that is approved for
treating hypertension. Prazosin crosses the blood–brain barrier
where it is thought to have CNS effects. It is used in psychiatry
mainly in the treatment of nightmares in posttraumatic stress
disorder. Side effects are generally those associated with
hypotension.
GUANFACINE (INTUNIV)
Guanfacine is an α-2 (mostly α-2A) norepinephrine receptor
agonist. It is posited to improve ADHD through actions in
prefrontal cortex. This medication is also used as an
antihypertensive.
MEDICATIONS USED TO TREAT ATTENTION-

DEFICIT HYPERACTIVITY DISORDER
Medications approved for treating ADHD include the
aforementioned guanfacine, atomoxetine, and psychostimulants.
ATOMOXETINE
Atomoxetine (Strattera) is a selective norepinephrine reuptake
inhibitor medicine approved for treating attention-deficit disorder.
Similar medications are approved in other countries for treating
depression; and although atomoxetine is used off-label in the
United States for treating depression, its efficacy is unknown. Like
other medications that have monoamine reuptake as a primary
mechanism of action (e.g., selective serotonin reuptake inhibitors),
atomoxetine has been associated with an increased risk of suicide
in children and adolescents and requires careful monitoring,
especially during the initiation or tapering of therapy.
PSYCHOSTIMULANTS
Psychostimulants are used in psychiatry to treat attention-deficit
disorder, narcolepsy, excessive daytime sleepiness, and some forms
of depression. Commonly used psychostimulants are
dextroamphetamine (Dexedrine), methylphenidate (Ritalin), and
Adderall (a mixture of amphetamines). The mechanism of action of
these medications appears to occur through their alterations of CNS
monoamine function. Their primary mechanism of action is
thought to be facilitating endogenous neurotransmitter release
(rather than acting as a direct agonist). Psychostimulants have the
liabilities of inducing tolerance and psychological dependence,
which may lead to abuse. The side effects of these medications are
due largely to their sympathomimetic actions and include
tachycardia, insomnia, anxiety, hypertension, and diaphoresis.
Weight loss may be an unwanted side effect in young children, but
a desirable one in overweight adults.
MEDICATIONS USED TO TREAT SPECIFIC

SUBSTANCE USE DISORDERS
NALTREXONE
Naltrexone (ReVia; Vivitrol) is a μ-opioid antagonist that is
approved for the treatment of alcohol dependence and opioid
dependence. In alcohol dependence (now alcohol use disorder), it is
used to prevent alcohol relapse and to lessen the severity of a
relapse in individuals with alcohol dependence. Naltrexone
treatment is initiated once a patient has been detoxified from
alcohol. For individuals coabusing opiates or who are receiving
opiates for medical reasons, naltrexone treatment should not be
initiated until at least 1 week after the last opiate exposure (an
opiate antagonist can precipitate severe opiate withdrawal if given
to opiate-dependent persons). Naltrexone reduces alcohol craving,
reduces the probability of an alcohol relapse, and reduces the
severity of a relapse when one occurs. Naltrexone, like all
treatments for alcohol use disorder, works best when combined
with psychosocial interventions.
BUPRENORPHINE
Buprenorphine is used for the treatment of opiate addiction/opiate
use disorder. As a partial opioid agonist, buprenorphine has a role
in opiate detoxification. Unlike methadone maintenance treatment
for opiate dependence/opiate use disorder (which can only be used
in specialized methadone treatment centers), oral buprenorphine
(Subutex), or a formulation containing buprenorphine and naloxone
(Suboxone), are available for use in outpatient office-based
practices. The parental form of buprenorphine (Buprenex) is used
intramuscularly for treating symptoms of opiate withdrawal in
some circumstances. Because buprenorphine is a partial opioid
agonist, it has a greater safety margin with regard to side effects
such as respiratory depression. Mixing buprenorphine with
naloxone is designed to prevent diversion of the buprenorphine
tablets for recreational intravenous injection. If taken as an oral
sublingual preparation as prescribed, the naloxone (an opiate
antagonist) in the medication has poor absorption and therefore
does not interfere with the desired therapeutic effect of
buprenorphine. If the oral pill is crushed or otherwise converted to
an injectable form, however, the naloxone component (as a μ-
opioid antagonist) is effective, blocking burprenorphine’s effects as
a partial agonist at the μ-opioid receptor.
Methadone
Methadone is an opioid agonist and has some antagonist properties
for the N-methyl-d-aspartate receptor. It is used as maintenance
treatment for opioid use disorder. Methadone has a black-box
warning from the U.S. Food and Drug Administration for use in
pregnant women because it can lead to neonatal withdrawal
syndrome. Because of this concern, buprenorphine is increasingly
used for pregnant women requiring opiate maintenance therapy.
ACAMPROSATE
Acamprosate (Campral) is used in the treatment of alcohol
dependence. Acamprosate is indicated for maintaining abstinence
in previously alcohol-dependent subjects who are abstinent at
treatment initiation. Acamprosate may work via numerous
mechanisms, including as a modulator of glutamate function. This
medication seems to reduce the craving and urge to drink in
patients recently withdrawn from alcohol and helps maintain
abstinence and make relapse less severe. Acamprosate should be
combined with psychosocial interventions in the treatment of
alcoholism.
DISULFIRAM
Disulfiram (Antabuse) is used to prevent alcohol ingestion through
the fear of the consequences of ingesting alcohol while taking
disulfiram (Table 19-1). Disulfiram blocks the oxidation of
acetaldehyde, a step in the metabolism of alcohol. The buildup of
acetaldehyde produces a toxic reaction, making an individual who
ingests alcohol while taking disulfiram severely ill within 5 to 10
minutes. Symptoms include flushing, headache, sweating, dry
mouth, nausea, vomiting, and dizziness. In more severe reactions,
chest pain, dyspnea, hypotension, and confusion occur. Fatal
reactions, although rare, can occur. Disulfiram use should be
restricted to carefully selected patients who are highly motivated
and who fully understand the consequences of drinking alcohol
while taking disulfiram. Side effects in the absence of alcohol
ingestion include hepatitis, optic neuritis, and impotence.
VARENICLINE (CHANTIX)
Varenicline is approved for the treatment of smoking cessation. Its
mechanisms of action include partial agonist activity at α-4 β-2
nicotinic receptors and the ability to increase dopamine release.
MEDICATIONS USED TO TREAT INSOMNIA

Most benzodiazepines (see Chapter 14) have hypnotic (sleep-
inducing) properties including decreasing sleep-onset latency (time
to go to sleep), decreasing number and duration of nocturnal
awakenings, and increasing overall sleep time. Tolerance to these
medications develops rapidly, and sleep architecture during their
use is abnormal. There are also nonbenzodiazepine hypnotics:
zolpidem (Ambien, Ambien-CR), zaleplon (Sonata), and
eszopiclone (Lunesta). These drugs are γ-aminobutyric acid
(GABA) receptor modulators. Naturally occurring melatonin in a
pill form is also used to induce sleep. Ramelteon (Rozerem) is
believed to work by binding to melatonin receptors in the
suprachiasmatic nucleus. Melatonin is also used, but it has variable
efficacy. The GABA modulator sleep aids have been associated
with the formation of tolerance and dependence. Ramelteon may
not have this problem, but further experience and studies are
needed to be certain. Some sedating tricyclic antidepressants (e.g.,
amytriptiline) and trazadone have been used to treat insomnia.
They do not appear to promote tolerance and dependence, but may
not promote physiologically normal sleep.
MEDICATIONS USED TO TREAT

NARCOLEPSY
Of the mediations approved for narcolepsy, modafinil and
amodafinil are used much more broadly for daytime sleepiness of
many origins.
MODAFINIL (PROVIGIL)
Modafinil is approved for excessive daytime sleepiness in
narcolepsy, obstructive sleep apnea, and shift work sleep disorder.
The mechanism and site of action of modafinil is not fully known
but it may have dopamine reuptake inhibition properties and its
mechanism requires α-receptors. The hypothalamus is the likely
site of action.
Armodafinil (Nuvigil)
Armodafinil is the R-enantiomer of modafinil, and is thought to
work by a similar mechanism. It has similar indications for use.
SODIUM OXYBATE (XYREM)

Sodium oxybate is approved for treating excessive daytime
sleepiness and cataplexy in narcolepsy. Sodium oxybate is a
GABA derivative that has partial agonist activity at GABA-B
receptors and the γ-hydroxybutyrate receptor. It has CNS
depressant and respiratory depressant properties; because of the
dangers of overdose, it is available only via a special program that
restricts use. It is dosed at night to promote sleep. The drug may
improve daytime sleepiness in narcolepsy by increasing the
proportion of slow wave sleep.
MEDICATIONS USED TO TREAT DEMENTIA

A number of medications are available in the United States for the
treatment of cognitive dysfunction associated with AD. Donepezil
(Aricept), rivastigmine (Exelon), and galantamine (Reminyl) are
reversible inhibitors of the enzyme acetylcholinesterase, and are
used to enhance cognition in patients with mild-to-moderate
dementia of the Alzheimer’s type. The acetylcholinesterase
inhibitors improve cognitive function and global function.
Rivastigmine also inhibits butyrylcholinesterase, a property that
may contribute greater efficacy to rivastigmine in later stages of
AD. Galantamine also has activity at nicotinic cholinergic receptors
that may be clinically significant. Some of the cognitive deficits in
AD result from loss of cholinergic neurons in the basal forebrain
that project to the cerebral cortex and hippocampus, which results
in a deficiency of cholinergic neurotransmission (Fig. 19-1). By
inhibiting the enzyme or enzymes that hydrolyze synaptic
acetylcholine, these drugs are thought to raise synaptic
concentrations of acetylcholine in the remaining cholinergic
neurons. Initially, these drugs reduce cognitive impairment;
however, this effect wanes with the progressive loss of cholinergic
neurons. Common side effects include gastrointestinal upset and
other cholinomimetic effects including bradycardia and increased
gastric acid secretion.
FIGURE 19-1. The cholinergic diffuse modulatory systems arising
from the basal forebrain and brain stem. (From Bear MF, Connors
BW, Paradiso MA. Neuroscience, 4th ed. Philadelphia, PA: Wolters
Kluwer, 2015.)
MEMANTINE (NAMENDA)
Memantine is an antagonist at the excitatory glutamatergic NMDA
receptor. Memantine is approved for the treatment of moderate-to-
severe dementia of the Alzheimer’s type. Antagonism of the
NMDA receptor may help prevent glutamate-mediated
excitotoxicity and improve function of neurons involved in some
forms of memory (e.g., the hippocampus). Emerging case reports
suggest that memantine may also have efficacy in treating catatonia
that is refractory to benzodiazepines.
CAPRYLIDENE (AXONA)
Caprylidene is a medical food that is approved for dietary
management of metabolic processes associated with mild or
moderate AD. The medical food works by increasing ketones as an
alternative energy source for the brain.
THYROID HORMONES
Thyroid hormones are used primarily in psychiatry to augment the
effects of antidepressants. They may also be used as adjuncts in
treating rapid-cycling bipolar disorder.
Although clinical hypothyroidism can mimic the symptoms of
depression, some individuals without clinical hypothyroidism may
respond to thyroid augmentation. The theoretic basis for using
thyroid hormones lies in the finding of altered hypothalamic–
pituitary–adrenal axis functioning in depressed individuals.
Although there is debate as to their relative efficacy, both triiodo
thyronine and tetraiodo thyronine cross the blood–brain barrier.
Tetraiodo thyronine has been shown to be of use in conjunction
with lithium to improve clinical control of rapid-cycling bipolar
disorder. Side effects at low doses are minimal; when dosages
result in overreplacement, symptoms of hyperthyroidism emerge.
KEY POINTS
A number of medications are available to treat AD,
ADHD, insomnia, narcolepsy, and substance use
disorders. These drugs target brain chemistry
believed to be related to the disorder’s underlying
pathophysiology.
Medications that affect various neurotransmitters
can be used to counteract the side effects of other
psychotropic medications.
CLINICAL VIGNETTES
VIGNETTE 1
Some of the cognitive deficits in Alzheimer’s disease (AD) (major
neurocognitive disorder due to AD) are caused by loss of cholinergic
neurons in the basal forebrain that project to the cerebral cortex and
hippocampus. One of the current mainstays of therapy is to increase
the effectiveness of acetylcholine transmission in the remaining
neurons.
1. Which of the following medication is an effective treatment for

AD?
a. Donepezil
b. Diphenhydramine
c. Buprenorphine
d. Acamprosate
ANSWERS
1. Answer A:
Donepezil is an acetylcholinesterase inhibitor that inhibits the
breakdown of acetylcholine and therefore increases synaptic
concentrations. Donepezil does not alter the course of AD but does
produce memory improvements. Diphenhydramine is an antihistamine
that has anticholinergic properties. Anticholinergic medications can
worsen memory in AD and also precipitate delirium. Buprenorphine is
a partial μ-opiate receptor agonist that is used for maintenance
therapy in opioid use disorder and that also has some analgesic
properties. Acamprosate is a glutamate modulator that is used for
maintenance of sobriety in alcohol use disorder/alcohol dependence.
INTRODUCTION
This chapter describes a group of major adverse reactions
associated with use of psychiatric medications. Minor adverse
reactions and side effects are outlined in the chapters on the
respective medications. Although the adverse drug reactions
discussed later (with the exception of serotonin syndrome) are most
commonly produced by antipsychotic medications, they may occur
in response to other medications. The major adverse drug reactions
to antipsychotics, their risk factors, onset, and treatment are
outlined in Table 20-1.
TABLE 20-1. Medication-Induced Movement Disorders

Disorder Risk Factors Onset Treatment
Dystonia High-potency First few days of IM/IV benztropine
antipsychotics therapy or diphenhydramine
Young men Severe
laryngospasm may
require intubation
Akathisia Recent First month of Propranolol,
increase/onset therapy lorazepam (maybe
of medication anticholinergics)
dosing
EPS High-potency First few weeks of Anticholinergics
antipsychotics therapy Lowering
Elderly antipsychotic
Prior episode dosage or changing
of EPS to lower potency
antipsychotic
Amantadine
NMS High-dose Usually within the Discontinuing
antipsychotics, first few weeks; can antipsychotic
rapid-dose occur at any point in medication
escalation, or antipsychotic therapy Supportive
IM injection symptom
of management
antipsychotics Dantrolene,
Agitation, bromocriptine
dehydration May require
Prior episode intensive care
of NMS
TD Elderly Usually after years of Lowering dosage of
Long-term treatment antipsychotic
antipsychotic Changing
treatment antipsychotics
Female Changing to
African clozapine
American
Mood
disorders
EPS, extrapyramidal syndrome; IM, intramuscular; IV, intravenous; NMS, neuroleptic malignant
syndrome; TD, tardive dyskinesia.
DYSTONIA
Dystonia is a movement disorder induced by dopamine receptor 2
antagonist medications and is characterized by muscle spasms.
Dystonia commonly involves the musculature of the head and
neck, but may also include the extremities and trunk. Symptoms
may range from a mild subjective sensation of increased muscle
tension to a life-threatening syndrome of severe muscle tetany and
laryngeal dystonia (laryngospasm) with airway compromise. The
muscle spasms may lead to abnormal posturing of the head and
neck with jaw muscle spasm. Spasm of the tongue leads to
macroglossia and dysarthria; pharyngeal dystonia may produce
impaired swallowing and drooling. Ocular muscle dystonia may
produce oculogyric crisis.
Risk factors include use of high-potency antipsychotics, with
young men at increased risk. The condition usually develops early
in drug therapy (within days).
Treatment of dystonia depends on the severity of the symptoms.
Most commonly, the muscle spasms are mild and respond to oral
doses of anticholinergic medication. In more severe cases,
intramuscular anticholinergic medication (benztropine or
diphenhydramine) can be used. If laryngospasm is present,
intravenous anticholinergic medication is used. Some cases may
require intubation if respiratory distress is severe. Discontinuation
of the precipitating antipsychotic is sometimes necessary; in other
cases, the addition of anticholinergic medications on a standing
basis prevents the recurrence of dystonia.
AKATHISIA
Akathisia, a common side effect produced by antipsychotic
medications, is also caused by serotonin reuptake inhibitors.
Akathisia consists of a subjective sensation of inner restlessness or
a strong desire to move one’s body. Individuals with akathisia may
appear anxious or agitated. Most commonly, it is seen shortly after
the initiation of an antipsychotic medication, particularly in young
male patients. They may pace or move about, unable to sit still.
Akathisia can produce severe dysphoria and anxiety in patients and
may, if unrecognized, drive them to become assaultive or to
attempt suicide. It is important to diagnose akathisia accurately;
because if mistaken for agitation or worsening psychosis,
antipsychotic dosage may be increased with resultant worsening of
the akathisia.
Risk factors for akathisia include a recent increase in
medication dosing or the recent onset of medication use. Most
cases occur within the first month of drug therapy, but akathisia
can occur at any time during treatment.
Treatment consists of reducing the medication (if possible) or
using either β-blockers (propranolol is commonly used) or
benzodiazepines (especially lorazepam). Although there is some
debate regarding their efficacy, anticholinergics (diphenhydramine
or benztropine) are also used frequently. Emerging medications for
treating akathisia include mirtazapine and trazodone.
EXTRAPYRAMIDAL SYNDROME
Extrapyramidal syndrome (EPS), also known as neuroleptic-
induced Parkinsonism or other drug-induced Parkinsonism,
consists of the development of the classic motor symptoms of
Parkinson’s disease in response to neuroleptic (antipsychotic) use
or medications such as metoclopramide. Typical antipsychotics
have the highest rate of EPS and atypical antipsychotics have a
lower risk. The most common symptoms are rigidity and akinesia,
which occur in as many as half of all patients receiving long-term
neuroleptic therapy. A 3- to 6-Hz tremor may be present in the
head and face muscles or the limbs. Akinesia or bradykinesia is
manifested by decreased spontaneous movement and may be
accompanied by drooling. Rigidity consists of the classic
Parkinsonian “lead pipe” rigidity (rigidity that is present
continuously throughout the passive movement of an extremity) or
cogwheel rigidity (rigidity with a catch-and-release character).
Risk factors for the development of EPS include the use of
high-potency antipsychotics, increasing age, and a prior episode of
EPS. EPS usually develops within the first few weeks of therapy.
Treatment consists of reducing the dosage of antipsychotic (if
possible) and adding anticholinergic medications or amantadine to
the regimen.
NEUROLEPTIC MALIGNANT SYNDROME

Neuroleptic malignant syndrome (NMS) is an idiosyncratic and
potentially life-threatening complication most commonly
associated with antipsychotic drug use. NMS may occur
spontaneously, however, in response to any medication that blocks
dopamine receptors and in response to reductions or changes in
dopamine agonist medications. Symptoms of NMS may develop
gradually over a period of hours to days and can often overlap with
symptoms of general medical illness. The major clinical findings in
patients with NMS are presented in Table 20-2. Many symptoms of
NMS are nonspecific and overlap with symptoms common to other
psychiatric and medical conditions. The diagnosis of NMS is also
complicated by the waxing and waning nature of the clinical
picture.
TABLE 20-2. Neuroleptic Malignant Syndrome

Autonomic
Tachycardia, other cardiac arrhythmias
Hypertension
Hypotension
Diaphoresis
Fever progressing to hyperthermia
Motor
Rigidity/dystonia
Akinesia
Mutism
Dysphagia
Behavioral
Agitation
Incontinence
Delirium
Seizures
Coma
Laboratory
Increased creatine kinase
Abnormal liver function tests
Increased white blood cell count
Decreased serum iron
Autonomic instability coupled with motor abnormalities is

essential to the diagnosis of NMS. Autonomic alterations can
include cardiovascular alterations with cardiac arrhythmias and
labile blood pressure. Low-grade fever progressing to severe
hyperthermia may also be present. Motor findings may overlap
with other motor abnormalities in psychiatric illness; for example,
rigidity/dystonia can be confused with simple dystonia or with
EPS. Mutism can be a sign of severe psychosis or catatonia alone,
although this does occur with NMS. Behavioral features such as
agitation can also overlap with other psychiatric syndromes;
however, the presence of delirium or seizures is a harbinger of
more serious general medical illness (including drug withdrawal)
or NMS. Laboratory findings may reveal an increased creatine
kinase secondary to myonecrosis from sustained muscular rigidity.
Liver enzymes may be elevated, but their relation to NMS is
unclear. Leukocytosis is also often present.
Risk factors for the development of NMS (see Table 20-1)
include the use of high-dose antipsychotics, rapid-dose escalation,
intramuscular injection of antipsychotics, dehydration, agitation, or
a prior history of NMS. Some factors may be related to severity of
illness (e.g., severely ill patients often have poor oral intake and
become dehydrated, are more likely to be placed in restraints, and
require intramuscular injection of an antipsychotic) rather than
causative factors. Although NMS is most common during the first
few weeks of antipsychotic drug therapy, it can occur at any time
during therapy.
Treatment of this potentially fatal disorder is largely supportive.
Specific interventions include discontinuation of antipsychotics (an
option that may take a long period of time in individuals treated
with depot antipsychotics); restoration of recently withdrawn
dopamine agonists; dantrolene (a muscle relaxant) is used to
decrease rigidity and myonecrosis; and bromocriptine (a dopamine
agonist) is sometimes used to reverse dopamine-blocking effects of
antipsychotics. Symptom management including intensive care
with cardiac monitoring and intubation may be necessary.
Symptoms of NMS overlap with serotonin syndrome (Table 20-3);
however, in NMS, muscular rigidity and increased creatine kinase
are prominent. In addition, serotonin syndrome develops in
response to the use of medications that affect serotonin function
(especially monoamine oxidase inhibitors [MAOIs]), whereas
NMS develops in response to antidopaminergic medications. In
patients using both MAOIs and antipsychotics (e.g., refractory
psychotic depression), the diagnosis can be quite difficult.
TABLE 20-3. Serotonin Syndrome
Autonomic
Tachycardia
Hypertension
Diaphoresis
Fever progressing to hyperthermia
Motor
Shivering
Myoclonus
Tremor
Hyperreflexia
Oculomotor abnormalities
Behavioral
Restlessness
Agitation
Delirium
Coma
TARDIVE DYSKINESIA
Tardive dyskinesia (TD) is a movement disorder that develops with
long-term use of dopamine antagonists, most commonly
antipsychotics; rarely, it occurs spontaneously in elderly
individuals who have not taken antipsychotic medications. TD
consists of constant, involuntary, stereotyped choreoathetoid
(dance-like) movements most frequently confined to the head and
neck musculature. At times, the extremities and respiratory and
oropharyngeal musculature are also involved.
Risk factors include long-term treatment with neuroleptics,
increasing age, female gender, and the presence of a mood
disorder. Although TD is reversible in some cases, especially in
younger individuals, it often becomes permanent. Treatment
consists of changing antipsychotics, lowering the dosage, or
switching to clozapine. Clozapine, which appears to work by a
mechanism different from other antipsychotics, may reduce or
eliminate the abnormal movements of TD.
SEROTONIN SYNDROME
Serotonin syndrome results from high synaptic concentrations of
serotonin. The syndrome can result from a single use of
medications or illicit drugs that are serotonergically active, but it
most commonly occurs when multiple medications that alter
serotonin metabolism are used simultaneously (Table 20-4).
Classically, this syndrome is produced when other serotonin-
altering medications are used with MAOIs. This syndrome, which
can be life-threatening, consists of symptoms outlined in Table 20-
3. These include severe autonomic instability, motor abnormalities,
and behavioral changes. The course of the disorder can exist on a
continuum from very mild symptoms to becoming malignant and
ending in coma and death. A similar syndrome occurs when
MAOIs are used with meperidine or dextromethorphan and perhaps
other opiates.
TABLE 20-4. Serotonergically Active Agents

Mechanism of Action Example Drug or Drug Category
Drugs that decrease Monoamine oxidase inhibitors, linezolid
serotonin metabolism
Drugs that decrease SSRIs, SNRIs, tricyclic antidepressants,
serotonin reuptake opioids, antiemetics
Drugs with serotonin agonist Buspirone, vilazodone
activity
Drugs that increase serotonin Amphetamines,
release methylenedioxymethamphetamine
(ecstasy)
SNRI, serotonin norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Data from Wang RZ, Vashistha V, Kaur S, et al. Serotonin syndrome: preventing, recognizing, and
treating it. Cleve Clin J Med. 2016;83(11):810–817, Table 1. doi:10.3949/ccjm.83a.15129.
Serotonin syndrome has many similarities to NMS, but clues to

the differential diagnosis may arise from the history of medication
exposure and the clinical symptoms. NMS occurs following or
during the use of antipsychotic medication, whereas serotonin
syndrome occurs through use of MAOIs or other serotonergic
agents. NMS tends to have a gradual onset, whereas serotonin
syndrome can be abrupt. Serotonin syndrome may present with
shivering, hyperreflexia, and clonus. Prominent gastrointestinal
symptoms (e.g., nausea and diarrhea) may suggest serotonin
syndrome. Muscular rigidity can develop in severe cases of
serotonin syndrome, thus mimicking NMS.
Risk factors for serotonin syndrome, other than combining
MAOIs with other serotonin-altering medications, are not known.
Treatment for serotonin syndrome is largely supportive and
may require intensive care with cardiac monitoring and mechanical
ventilation. The serotonin 2A receptor antagonist cyproheptadine
shows efficacy in treating this condition. The offending
medications should be discontinued.
METABOLIC EFFECTS
Many psychotropic agents appear to affect energy balance in the
body, leading to weight gain and potentially the metabolic
syndrome (obesity, insulin resistance, and hyperlipidemia). The
most problematic agents in this regard are olanzapine and
clozapine, although all atypical antipsychotics and some mood
stabilizers (lithium and valproic acid) are associated with increased
body mass and may precipitate diabetes. The mechanisms
underlying the weight gain and glucose dysregulation are unclear.
Antipsychotics are typically used in patients who have psychosis
and who are also less physically active because of the illness. Some
antipsychotics also appear to increase appetite, sometimes
substantially. Antipsychotics may also decrease metabolism
(although this is not proved). Generally, the benefits of
antipsychotic therapy for psychotic disorders outweigh the risks of
metabolic effects. Patients and their involved families should be
informed of the risks before therapy initiation. Baseline body
measurements and fasting lipid and glucose levels should be
checked at initiation and periodically during treatment. Medication
choices should be made on the basis of a thoughtful calculation of
the risks and the benefits of the therapy in question.
KEY POINTS
Major adverse drug reactions occur most
commonly in psychiatry with the use of
antipsychotics and serotonin-altering medications.
Antipsychotics can cause dystonia, akathisia,
EPS, NMS, TD and weight gain, or diabetes.
Serotonin-altering medications can cause
akathisia and serotonin syndrome.
All of these adverse drug reactions are reversible
though treatment, except for TD, which may be
permanent.
CLINICAL VIGNETTES
VIGNETTE 1
You are asked to see in follow-up at your outpatient practice a
27-year-old man who was discharged 2 days ago from a psychiatric
hospital with a diagnosis of brief psychotic disorder, rule out
schizophrenia. The patient reports to you that he has developed a
hand tremor. When you meet him, you notice that he has a tremor
that looks like he is rolling a pill. You also notice that he is walking
very stiffly and appears to be having trouble initiating his
movements.
1. Which of the following medications would be most likely to have
caused this condition?
a. Lorazepam
b. Benztropine
c. Quetiapine
d. Clozapine
e. Haloperidol
You switch the patient’s medication to risperidone, an atypical
antipsychotic that is less likely to produce extrapyramidal
syndrome (EPS). Before he can follow-up with you to assess the
effects of switching to risperidone, he is taken to the emergency
room by EMS after becoming agitated and threatening. In the
emergency room, he receives multiple intramuscular injections of
haloperidol and multiple injections of intramuscular lorazepam. He
appears dehydrated and disheveled. He has a core temperature of
101°F, a blood pressure of 200/110 mm Hg, and a heart rate of 128
beats per minute. He is able to move all four extremities distally
and proximally and responds to deep tissue pain, but little else. His
workup includes a complete metabolic serum panel. His creatine
phosphokinase level is greatly elevated at 110,000 units per liter.
2. His blood pressure becomes unstable, and he is moved to the
intensive care unit. The most likely diagnosis is:
a. Serotonin syndrome
b. Neuroleptic malignant syndrome (NMS)
c. Dystonia
d. Tardive dyskinesia (TD)
e. Pneumonia
VIGNETTE 2
A 19-year-old man is seen on rounds on a psychiatric unit after being
admitted two nights before. He was diagnosed with psychotic disorder,
not otherwise specified and begun on risperidone 1 mg twice per day.
The nurse asked you to see him first because he had been “agitated
all morning.” When you enter his room, you find him pacing the floor.
He tells you that he feels restless and that he has to keep moving to
feel better. Other than pacing, he is not exhibiting any tremors or other
movements of the extremities. Although he appears agitated, his
psychotic symptoms, which include hallucinations and delusions, do
not appear to have worsened since admission. Vital signs are within
normal limits and he is afebrile. A serum creatine phosphokinase is
drawn and is normal.

a. Dystonia
b. Parkinsonism
c. Akathisia
d. NMS
e. TD
ANSWERS
1. Answer E:
The patient has developed EPS, also known as neuroleptic-induced
parkinsonism, a drug-induced condition resembling Parkinson’s
disease. The “pill-rolling” tremor, festinating gait, and difficulty initiating
movements are all symptoms of Parkinson’s disease. A 3- to 6-Hz
tremor may be present in the head and face muscles or the limbs.
Akinesia or bradykinesia are manifested by decreased spontaneous
movement and may be accompanied by drooling. Because low
cerebral dopamine levels cause the condition, drugs that block
dopamine receptors are most likely to mimic the disease. Neither
lorazepam nor benztropine block dopamine receptors. Both quetiapine
and clozapine block dopamine receptors, but they only weakly block
dopamine receptors and are less likely to cause EPS. Haloperidol, a
potent dopamine 2 receptor blocker, is most likely to cause the
syndrome.
2. Answer B:
Autonomic instability coupled with motor abnormalities is essential to
the diagnosis of NMS. NMS can occur at any time during the use of
antipsychotic medications. It is most frequently seen during periods of
dehydration or rapid escalation of antipsychotic dose. Serotonin
syndrome may present with shivering, hyperreflexia, and clonus.
Prominent gastrointestinal symptoms (e.g., nausea and diarrhea) may
suggest serotonin syndrome. Muscular rigidity can develop in severe
cases of serotonin syndrome, thus mimicking NMS. Dystonia is a
neuroleptic-induced movement disorder characterized by muscle
spasms. TD is a movement disorder that develops with long-term use
of dopamine antagonists, most commonly antipsychotics. TD consists
of constant, involuntary, stereotyped choreoathetoid (dance-like)
movements most frequently confined to the head and neck
musculature. At times, the extremities and respiratory and
oropharyngeal musculature are also involved. Pneumonia may occur
as a secondary consequence of NMS but the clinical picture is not
suggestive of pneumonia.
1. Answer C:
This patient exhibits the classic symptoms of akathisia, a common
side effect of antipsychotic medications. Patients with this side effect
exhibit agitation, restlessness, and pacing. They usually endorse an
inner feeling of restlessness (often localized to the legs). It is important
to distinguish akathisia from restlessness and agitation caused by
worsening psychosis or anxiety. Other movement disorders, such as
dystonia (muscle spasm), tardive dyskinesia (slow, involuntary muscle
movements), or parkinsonism (pill-rolling tremor, festinating gait,
masked facies), should always be ruled out in patients taking
neuroleptics. Patients with NMS can present with agitation or motor
excitability, but the absence of fever and a normal serum creatine
phosphokinase level make this diagnosis unlikely.
INTRODUCTION
There are a large number of competing theories influencing
contemporary psychotherapeutic thinking. Psychotherapies derived
from psychoanalytic, cognitive, and behavioral theories are the
most widely used. Short-term psychodynamic therapy, cognitive-
behavioral interventions, and interpersonal therapy have the
strongest empirical verification for specific psychiatric conditions.
PSYCHOLOGICAL THEORIES
PSYCHOANALYTIC/PSYCHODYNAMIC THEORY
The principal theorist responsible for launching psychoanalysis as a
technique and psychodynamic theory in general is Sigmund Freud.
Freud’s theories proposed that unconscious motivations and early
developmental influences were essential to understanding behavior.
Freud’s original theories have proved quite controversial and have
led to the creation of various alternative or derivative theories
subsumed by three major schools of psychodynamic thinking.
TWENTIETH-CENTURY SCHOOLS OF
PSYCHODYNAMIC PSYCHOLOGY
There are three major 20th-century psychodynamic schools: drive
psychology, ego psychology, and object relations theory.
Drive Psychology
Drive psychology posits that infants have sexual (and other) drives.
This theory proposes that sexual and aggressive instincts are
present in each individual and that each individual passes
sequentially through psychosexual developmental stages (oral,
anal, phallic, latency, and genital). Included in drive psychology is
conflict theory, which proposes to explain how character and
personality development are influenced by the interaction of drives
with the conscience and reality.
Ego Psychology
Freud eventually developed a tripartite theory of the mind in which
the psychic structure was composed of the id, ego, and superego.
Under this theory, the id is the compartment of the mind containing
the drives and instincts. The superego contains the sense of right
and wrong, largely derived from parental and societal morality. The
ego is responsible for adaptation to the environment and for the
resolution of conflict. A major function of the ego is the reduction
of anxiety. Ego defenses (Table 21-1) are proposed as psychic
mechanisms that protect the ego from anxiety. Some ego defenses
(e.g., sublimation) are more functional for the individual than
others (e.g., denial).
TABLE 21-1. Common Ego Defense Mechanisms

Denial Feelings or ideas that are distressing to the ego are
blocked by refusing to recognize evidence for their
existence.
Projection Feelings or ideas that are distressing to the ego are
attributed to others.
Regression Feelings or ideas that are distressing to the ego are
reduced by behavioral return to an earlier development
phase.
Repression Feelings or ideas that are distressing to the ego are
relegated to the unconscious.
Reaction Feelings or ideas that are distressing to the ego are
formation converted into their opposites.
Displacement Feelings or ideas that are distressing to the ego are
redirected to a substitute that evokes a less intense
emotional response.
Rationalization Feelings or ideas that are distressing to the ego are dealt
with by creating an acceptable alternative explanation.
Suppression Feelings or ideas that are distressing to the ego are not
dealt with, but they remain components of conscious
awareness.
Sublimation Feelings or ideas that are distressing to the ego are
converted to those that are more acceptable.
Object Relations Theory

Object relations theory (object refers to important people in one’s
life) departs from drive theory in that the relationship to an object
is motivated by the primacy of the relationship rather than the
object being a means of satisfying a drive. Child observation
furthered object relations theory, emphasizing concepts of
attachment and separation.
DEVELOPMENTAL THEORY
Erik Erikson made major contributions to the concept of ego
development. Erikson theorized that ego development persists
throughout one’s life and conceptualized that psychosocial events
drive change, leading to a developmental crisis. According to
Erikson’s model, individuals pass through a series of life cycle
stages (Table 21-2). Each stage presents core conflicts produced by
the interaction of developmental possibility with the external
world. Individual progress and associated ego development occur
with successful resolution of the developmental crisis inherent in
each stage. This model allows for continued ego development until
death.
TABLE 21-2. Erikson’s Life Cycle Stages

Trust vs. Birth– The infant has many needs, but does not have
mistrust 18 the power to have those needs met. The child is
months dependent on caretakers. If caretaking is
appropriate, a sense of trust and hope are
created. If inappropriate or inadequate, mistrust
develops.
Autonomy 18 The child is learning about the use of language
vs. shame months– and control of bowel and bladder function and
3 years walking. As a result, he or she begins to choose
to influence and explore the world. If caretaking
is appropriate, the child will develop a healthy
balance between exerting his or her autonomy
and feeling shame over the consequences of
exerting autonomy.
Initiative vs. 3–5 As the child develops increasing control of
guilt years language and walking, he or she has increased
initiative to explore the world. The potential for
action carries with it the risk of guilt at
indulging forbidden wishes.
Industry vs. 5–13 The child begins to develop a sense of self on
inferiority years the basis of the things he or she creates.
Caretaker influences are important in helping
the child develop a sense of mastery and
competence over creating.
Identity vs. 13–21 Corresponds to adolescence. How one appears
confusion years to others is important in this stage. There are
conflicts between one’s identity and the need to
gain acceptance.
Intimacy vs. 21–40 The anxiety and vulnerability produced by
isolation years intimacy are balanced against the loneliness
produced by isolation.
Generativity 40–60 If successful, the individual develops a positive
vs. years view of his or her role in life and a sense of
stagnation commitment to society at large. If unsuccessful,
individuals move through life without concern
for the greater welfare.
Ego 60 An individual accepts his or her life course as
integrity vs. years– appropriate and necessary. If this fails, the
despair death individual may regret or wish to relive some
part of life, leading to despair.
Modified from Sadock BJ, Sadock VA, Ruiz P. Synopsis of Psychiatry: Behavioral
Sciences/Clinical Psychiatry, 11th ed. Philadelphia, PA: Wolters Kluwer, 2015.
COGNITIVE THEORY
Cognitive theory recognizes the importance of the subjective
experience of oneself, others, and the world. It posits that irrational
beliefs and thoughts about oneself, the world, and one’s future can
lead to psychopathology.
In cognitive theory, thoughts or cognitions regarding an
experience determine the emotions that are evoked by the
experience. For example, the perception of danger in a situation
naturally leads to anxiety. When danger is truly present, anxiety
can be adaptive, leading to hypervigilance and self-protection.
When the situation is only perceived as dangerous (such as in fear
of public speaking), the resulting anxiety can be psychologically
paralyzing. A person may fear public speaking because of an
irrational fear that something disastrous will occur in public. A
principal type of irrational belief is a cognitive distortion (Table
21-3).
TABLE 21-3. Types of Cognitive Distortions

Arbitrary inference Drawing a specific conclusion without
sufficient evidence
Catastrophizing Assuming the worst possible outcome of an
experience
Dichotomous thinking A tendency to categorize experience as “all
or none”
Magnification/minimization Over- or undervaluing the significance of a
particular event
Overgeneralization Forming and applying a general or broad
conclusion on the basis of an isolated event
Self-referential thinking Thinking of one’s self as the focus of other
people’s interest, especially negative
interest
Based in part on Sadock BJ, Sadock VA, Ruiz P. Synopsis of Psychiatry: Behavioral
BEHAVIORAL THEORY
Behavioral theory posits that behaviors are fashioned through
various forms of learning, including modeling, classical
conditioning, and operant conditioning (Table 21-4). A behaviorist
might propose that, through operant conditioning, depression is
caused by a lack of positive reinforcement (as may occur after the
death of a spouse), resulting in a general lack of interest in
behaviors that were once pleasurable (or reinforced). Behavior
includes observable actions (not mental states) and can thus be
directly observed and measured. Behavior therapy may be useful
for agoraphobia, alcohol dependence, eating disorders, phobias,
paraphilias, psychotic conditions, and sexual dysfunction. Table
21-5 lists common behavioral therapy techniques.
TABLE 21-4. Important Concepts in Behavior Theory
Modeling A form of learning based on observing others and imitating
their actions and responses.
Classical A form of learning in which a neutral stimulus is
conditioning repetitively paired with a natural stimulus, with the result
that the previously neutral stimulus alone becomes capable
of eliciting the same response as the natural stimulus.
Operant A form of learning in which environmental events
conditioning (contingencies) influence the acquisition of new behaviors
or the extinction of existing behaviors.
TABLE 21-5. Common Behavioral Therapy Techniques

Systematic Patient approaches an anxiety-provoking stimulus after
desensitization entering a relaxed state, often in graded fashion.
Therapeutic Patient approaches anxiety-provoking stimulus in a
graded graded manner (but does not enter relaxed state before
exposure stimulus exposure).
Flooding Patient approaches/is exposed to anxiety-provoking
stimulus without using a graded approach.
Participant Patients view others and imitate behaviors of others (e.g.,
modeling watching another person approach an anxiety-provoking
stimulus).
Assertiveness Patient is trained to monitor and modify responses to
training circumstances that require acting in patient’s best
interests.
Positive Patients are provided a rewarding stimulus after
reinforcement engaging in a specific behavior.
Social skills Patients lacking social skills in specific dimensions
training systematically monitor and rehearse behavioral social
skills.
Aversion Patients are provided noxious stimuli (e.g., electric
therapy shocks) after engaging in a specific behavior.
Based in part on Sadock BJ, Sadock VA, Ruiz P. Synopsis of Psychiatry: Behavioral
PSYCHOTHERAPIES
SHORT-TERM PSYCHODYNAMIC PSYCHOTHERAPY

Short-term psychodynamic psychotherapy is a modern, manual-
based, systematic therapy that employs psychodynamic principles
to treat psychiatric conditions. The therapy is usually less than 40
sessions and has a focus on the present (i.e., early childhood and
past events are not the focus). Conflicts and themes are the target of
treatment and may encompass patterns of behavior or feeling,
recurrent themes in one’s life, and attention to wishes, dreams, and
fantasies. Short-term psychodynamic psychotherapy, when
properly applied by well-trained therapists, is broadly effective for
improving quality of social function, identified target symptoms,
and general psychiatric symptoms. Effects persist well beyond the
treatment period. Short-term psychodynamic therapy for depression
appears to be generally comparable to cognitive-behavioral therapy
(CBT) and interpersonal psychotherapy (IPT) (information to
follow) in efficacy, but individual patients may well show a
superior response to one form of therapy over another.
INTERPERSONAL THERAPY (IPT)

The interpersonal school arose as an outgrowth of object relations
theory. The interpersonal theorists emphasize that intrapsychic
conflicts are less important than one’s relationship to one’s sense of
self and to others. In other words, the relationships in a person’s
life are given primary importance in producing happiness or
misery. IPT for depression and related conditions has good
empirical validation, and it may work as well as medication
treatment and possibly better than CBT when interpersonal themes
are prominent.
BEHAVIORAL THERAPY
Behavioral approaches arose in the context of behaviorism (which
stipulates that behavior can be explained without consideration of
internal mental states) and are founded on learning theory.
Behavioral therapists focus on behavior modification and use
principals of classical and operant condition to achieve change. For
example, applied behavior analysis is the process of applying
behavioral principles to everyday situations to increase or decrease
target behaviors. These approaches are most frequently used in the
treatment of autism spectrum disorders, and include components of
discrete trial teaching, programming for generalization to the
natural environment, reinforcement, prompting and fading
strategies, and outcome-based decision making.
COGNITIVE-BEHAVIORAL THERAPY (CBT)

Cognitive and behavioral theories form part of the bases of CBT. It
involves the examination of cognitive distortions and the use of
behavioral techniques to treat common disorders such as major
depression. CBT has strong empirical validation and is effective in
the treatment of depression, social phobia, obsessive–compulsive
disorder (OCD), posttraumatic stress disorder, attention deficit
hyperactivity disorder, insomnia, bulimia nervosa, generalized
anxiety disorder, and panic disorder. CBT and pharmacotherapy,
such as antidepressant medications, are generally thought to be
synergistic, particularly with regard to the treatment of depression.
CBT as a treatment, however, appears to have long-lasting effects
in terms of preventing relapse that have not been well demonstrated
with medication treatment for most conditions.
DIALECTICAL-BEHAVIORAL THERAPY (DBT)

Dialectical-behavioral therapy (DBT) is a psychotherapy developed
specifically for the treatment of borderline personality disorder in
women. The foundation of DBT resides in CBT principles, but the
therapy encompasses empirical findings from multiple areas of
psychology, sociology, Zen philosophy, and dialectical philosophy.
Overall, DBT focuses on therapist and patient acceptance of the
patient as the foundation for developing skills for behavioral and
emotional change. DBT has strong empirical support in the
treatment of borderline personality disorder and is the first-line
psychotherapy for treating this condition.
THIRD WAVE THERAPIES

Third wave therapies commonly include acceptance and
commitment therapy, DBT, mindfulness-based cognitive therapy,
functional analytic psychotherapy, and behavioral activation
therapy. These therapies build off behavioral and cognitive
approaches; however, they are more contextual and experiential in
nature. In addition, the focus of change is broadened, so that these
approaches no longer focus on symptom reduction, but rather aim
to change the function of psychological events. For example, rather
than focusing on alleviating symptoms of depression, third wave
approaches might focus on engaging in a meaningful life despite
the presence of depressive symptoms. Through the development of
skills, patients are able to improve quality and quantity of
meaningful, value-guided, activity. These approaches are strengths-
based, and empower the patient with tools to foster mindfulness
and acceptance. For example, acceptance and commitment therapy
aims to change the relationship individuals have with thoughts,
feelings, and physical sensations that are feared or avoided. In
contrast to working to control these areas of difficulty, acceptance
and mindfulness strategies are used to teach patients to decrease
avoidance, loosen their attachment to maladaptive cognitions,
increase focus on the present, and engage in value-driven activity.
This transdiagnostic therapy has been empirically validated for the
treatment of a number of conditions, including anxiety, depression,
OCD, chronic pain, and psychosis.
KEY POINTS
Psychological theories are numerous, but those
derived from psychoanalytic, cognitive, and
behavioral theories are most widely used.
The psychoanalytic school emphasizes
unconscious motivations and early influences.
The object relations school emphasizes the
importance of relationships with other people.
The cognitive school emphasizes subjective
experience, beliefs, and thoughts.
The behavioral school emphasizes the influence of
learning.
CBT and IPT have the greatest empirical support
for treating depression and anxiety.
Brief psychodynamic psychotherapy has empirical
support for treatment of depression.
CLINICAL VIGNETTES
VIGNETTE 1
A 45-year-old woman presents with a 1-year history of the following
symptoms: sweating, trembling, sensation of choking, chest
discomfort, lightheadedness, derealization, fear of losing control, and
fear of dying. The symptoms develop over about 10 minutes in
situations where she feels trapped. The patient has been largely
disabled by the symptoms. She has been unable to pick up her
children at school, go shopping, or engage in her normal social
events. She would like to avoid using any type of medication. You
begin by teaching relaxation exercises and desensitization combined
with education aimed at helping the patient understand that her panic
attacks are the result of misinterpreting bodily sensations.
1. What is the name of this technique?

a. Exposure therapy
b. Psychodynamic therapy
c. Biofeedback therapy
d. Cognitive-behavioral therapy (CBT)
e. Classical conditioning
2. The patient becomes impatient with the progress of her

psychotherapy and also has less time to attend sessions because
of her work schedule. She now requests psychopharmacologic
management. She has been reading about the disorder and has
some familiarity with its pharmacologic management. Of the
appropriate medications, you choose a medication that acts as an
agonist at the γ-aminobutyric acid (GABA) receptor. Which of the
following medications meet these criteria?
a. Alprazolam
b. Mirtazapine
c. Imipramine
d. Paroxetine
e. Phenelzine
VIGNETTE 2
Tom was a 36-year-old business executive who experienced an
intense fear of public speaking. He had received several promotions
over the years and had become a spokesperson on behalf of his
company at a local, state, and national level. He had recently been
scheduled to give a talk to potential investors, but at the last minute
had suffered a severe panic attack and fled the building. This incident
lead him to go to his primary care provider (PCP), who recommended
he pursue psychotherapy. In therapy, Tom learned relaxation
techniques, engaged in gradual exposures to speaking situations, and
addressed negative self-talk (e.g., “I am going to make a fool of
myself”).
1. Tom began the recommended course of psychotherapy for his

presenting concerns. What type of psychotherapy was Tom
engaged in?
a. Interpersonal psychotherapy (IPT)
b. Dialectical-behavior therapy (DBT)
c. CBT
d. Short-term psychodynamic psychotherapy
2. What type of cognitive distortion does Tom’s thought “I am going

to make a fool of myself” represent?
a. Arbitrary inference
b. Dichotomous thinking
c. Overgeneralization
d. Magnification
e. Minimization
3. Which of the following represent a behavioral intervention that

Tom’s therapist likely recommended?
a. Have Tom go immediately back to the investors and arrange to
give the same talk as soon as possible.
b. Have Tom visualize speaking in front of different groups of
people beginning with family, friends, then colleagues, his boss,
and finally larger groups of investors.
c. Have Tom call his mother and ask if he ever experienced panic
symptoms as a child.
d. Have Tom exposed to noxious stimuli after avoiding or
escaping from speaking engagements.
e. Have Tom worry less about public speaking in general and
refocus his thoughts and behaviors on engaging in value-driven
activity.
4. What would Tom’s therapist likely NOT ask regarding Tom’s

thought (“I am going to make a fool of myself”)?
a. Is this always true?
b. What is the likelihood of this taking place?
c. What is the worst possible thing that might transpire?
d. Do you think your parent’s divorce and the resulting childhood
separation from your father contributes to your fear of public
speaking?
e. Are you being objective?
VIGNETTE 3
Julie is a 52-year-old graphic designer who recently transitioned jobs
and whose 17-year-old son just left for college. Recently she started
feeling low in mood and was finding it difficult to get motivated to go to
work, engage socially, or exercise. As a result, she was avoiding her
friends, and they gradually stopped calling altogether. Julie was also
fighting with her spouse daily and he had begun to threaten her with
divorce if she didn’t get help. Things she previously really enjoyed
doing were no longer enjoyable. Since everything was such an effort
to Julie, and when she did make the effort she didn’t enjoy it, she
began doing less and less. She began to feel hopeless about the
future, her mood became lower, and she found herself thinking “Why
bother? Does anyone even care about me?” at which point she
decided to engage in psychotherapy.
1. Julie sought therapy to help her improve her existing

interpersonal relationships and increase her social support
network. What type of psychotherapy was Julie engaged in?
a. IPT
b. DBT
c. CBT
d. Short-term psychodynamic psychotherapy
2. Which of the following is NOT a specific focus of the patient and

therapist in this type of therapy?
a. Current relationships and patterns of interaction
b. Communication style
c. Radical acceptance
d. Attachment style
e. Setting appropriate treatment goals
3. Which of the following does NOT represent one of the core IPT
problem areas?
a. Grief
b. Interpersonal disputes
c. Role transitions
d. Interpersonal sensitivity
4. Which of the following techniques is unique to the therapeutic

modality Julie was engaging in?
a. Therapeutic alliance
b. Encouragement of affect
c. Communication analysis
d. Free association
e. Developing a fear hierarchy
ANSWERS
1. Answer D:
The symptoms described are consistent with a panic attack. The
technique described is CBT. Subsequently, the patient will learn that
the sensations are innocuous and self-limited, which generally
diminishes the panicky response. Exposure therapy involves
incrementally confronting a feared stimulus. Classical conditioning is a
form of learning in which a neutral stimulus is repetitively paired with a
natural stimulus with the result that the previously neutral stimulus
alone then becomes capable of eliciting the same response as the
natural stimulus.
2. Answer A:
Alprazolam is a benzodiazepine and acts at the GABA receptor. It
may be effective in the treatment of panic and is widely used but,
given its increased risk for causing physiologic dependence and
addiction (benzodiazepine use disorder), it should be considered only
as a short-term alternative while other therapies are initiated.
Mirtazapine blocks the α-2 reuptake receptor and also has
postsynaptic activity. Imipramine is a tricyclic antidepressant and acts
mainly by blocking presynaptic reuptake of serotonin and
norepinephrine. Paroxetine is a selective serotonin reuptake inhibitor
and works mainly through blockade of the presynaptic serotonin
reuptake transporter. Phenelzine is a monoamine oxidase inhibitor
that blocks the presynaptic enzymes that catabolize norepinephrine,
dopamine, and serotonin.
1. Answer C:
CBT is a form of psychotherapy that focuses on how your thoughts
and your behaviors affect your mood. The basic idea of CBT is that if
you can change unhelpful thinking or behavior patterns, then you can
change how you feel. Significant research has proven CBT to be the
most effective treatment for phobias, panic attacks, and panic
disorder. In numerous studies, CBT has outperformed all other
psychological treatments, including antianxiety medication. Scientific
studies have consistently found that CBT is more effective at reducing
symptoms, the treatment is briefer in duration, and the results last
longer for more people, than traditional talk therapy or use of
anxiolytics. Cognitive-behavioral treatment for panic attacks and panic
disorder usually involves some combination of relaxation training,
cognitive restructuring, and exposures to feared stimuli.
2. Answer A:
When Tom thinks “I am going to make a fool of myself,” he is drawing
a specific conclusion about the future without sufficient evidence to
support it; hence, he is making an arbitrary inference. Arbitrary
inference is one of numerous specific cognitive distortions identified by
Beck (1979) that can be commonly presented in people with anxiety,
depression, and psychological impairments. Cognitive distortions
represent exaggerated or irrational thought patterns that cause
individuals to perceive reality inaccurately, and reinforce negative
emotions. Although dichotomous thinking, overgeneralization,
magnification, and minimization are also cognitive distortions with
negative effects on psychological well-being, they do not reflect the
process of drawing a specific conclusion without evidence to support
it. Dichotomous thinking refers to an individual’s tendency to
categorize experiences as all or none, or otherwise evaluating things
in extreme terms, such that it is all good or all bad. This is also
referred to as black and white thinking because there is a nothing in
between, or no shade of gray. Overgeneralization is when an
individual forms a general conclusion based on an isolated event. This
would not apply to Tom’s experience as his conclusion is based on a
series of events, including avoidance following the original panic
attack. Magnification and minimization refer to the pattern of giving
proportionally greater weight to a perceived failure, weakness, or
threat and lesser weight to a perceived success, strength, or
opportunity, such that the weight the anxious individual assigns to the
event differs from that assigned by others.
3. Answer B:
Having Tom visualize speaking in front of different groups of people
beginning with familiar others and gradually moving toward more
anxiety-provoking investors represents a graduated exposure
technique. The exposure is imaginal, in that it involves Tom imagining
the feared situation to evoke lower levels of anxiety. Imaginal
exposures can present a graduated approach, or “warm up” exposure,
before participating in in vivo exposures, such as actually speaking in
front of a crowd of others. The first step in implementing either
imaginal or in vivo exposures is to develop a hierarchy of fear-evoking
scenes arranged from least anxiety evoking to most anxiety evoking
and then to begin engaging in these exposures in a graduated way,
moving carefully and intentionally from mildly or moderately anxiety-
provoking, to most anxiety-provoking stimuli. The graduated exposure
to the feared objects, activities, or situations in a safe environment
helps reduce fear and decrease avoidance.
4. Answer D:
Tom’s CBT therapist would likely engage Tom in cognitive reframing
exercises to modify his distorted thinking. As such, he would challenge
Tom to examine the facts underlying his belief that he is going to
make a fool of himself. This would reasonably include questioning the
accuracy of the belief, exploring the feared consequences, and
decatastrophizing. It would not, however, focus on questions about
Tom’s childhood or developmental events that may affect his current
fears, as is more common of psychodynamic therapeutic approaches.
1. Answer A:
Julie engaged in IPT. IPT was initially developed as a brief therapy for
depression that focuses on interpersonal roles and relationships. IPT
has the following goals: to diagnose depression explicitly; to educate
the client about depression, its causes, and the various treatments
available for it; to identify the interpersonal context of depression as it
relates to symptom development; and to develop strategies for the
client to follow in coping with the depression. Because people with
depressive symptoms often experience problems in their interpersonal
relationships, IPT works to bring changes in the patient’s close
interpersonal relationships and develop new strategies for dealing with
significant others. Although the depression itself is not always a direct
result of negative relationships, relationship issues tend to be among
the most prevalent symptoms during the initial stages of depression.
Once addressed, strengthened relationships can serve as an
important support network throughout the remaining recovery process.
The targeted approach of IPT has demonstrated rapid improvement
for patients with problems ranging from mild situational depression to
severe depression.
2. Answer C:
Radical acceptance is a concept taken from DBT, wherein the patient
is taught to accept that reality is what it is, that the event or situation
causing you pain has a cause, that accepting life can be worth living
even with painful events in it. This is not a component of IPT. In
contrast, current relationships and patterns of interaction,
communication style, attachment style, and setting appropriate
treatment goals are all central components of IPT. In fact, there are a
number of specific techniques that are central to the success of IPT,
although not unique to IPT, including nondirective and directive
exploration, clarification, encouragement of affect, communication
analysis, role play, problem solving (or decision analysis), and the
therapeutic relationship.
3. Answer E:
IPT problem areas are grief, interpersonal disputes, role transitions,
and interpersonal sensitivity. Psychosocial stressors from any of the
problem areas can lead to psychological distress or psychiatric
syndromes, in particular when combined with an attachment disruption
in the context of a poor social support network. In IPT, grief is
considered to be relevant as a complicated bereavement, and
treatment involves helping the patient process the loss, communicate
the loss to others, recreate the lost relationship, and develop new
attachment. Interpersonal disputes relate to difficulty in forming and
maintaining relationships that often result in social isolation. IPT works
to assist the patient in resolving the dispute or helping the patient
move toward an acceptable dissolution of the relationship. Adaptation
to role transitions are a focus of treatment when the patient develops
psychological distress in the context of change. Invariably, the change
is experienced as a loss. Interpersonal interventions in role transitions
help the patient to define old and new roles, accept related emotional
loss and challenges, and develop and implement relevant skills.
Interpersonal sensitivity is demonstrated in many ways, including,
having few friends, repeated relationship failures, or conflict with
others. Interventions targeting interpersonal sensitivity help reduce the
patient’s isolation by optimizing the patient’s current relationship
functioning, by establishing new supportive relationships and resolving
acute interpersonal stressors.
4. Answer C:
Disordered communication is thought to be a primary reason for
interpersonal problems. In particular, the therapist engages in
communication analysis to uncover ambiguous and indirect verbal and
nonverbal communication that could be improved. Recent and past
incidents are explored to identify difficulties and to explore alternate
and more effective ways of communicating. The overall goals of
communication analysis are to identify communication patterns and
responses elicited from others; identify the client’s contribution to
communication problems; motivate the client to communicate more
effectively; and learn new and more effective communication skills.
1. A 68-year-old man presents in the emergency room with acute
agitation and confusion. On examination, the patient has dry
mucous membranes, bloodshot eyes, and an upper extremity
tremor. A head CT shows no infarct, lesion, or bleed. Electrolyte
levels reveal a negative anion gap. The electronic medical record
for the patient reveals a history of heart disease with mild
congestive heart failure, hypertension with use of a thiazide
diuretic, and a history of depression. The patient’s daughter
arrived at the emergency department a few hours after the
patient’s arrival and said that the patient had been diagnosed as
hypomanic and had been started on a medication by a
psychiatrist 3 weeks ago. She also said that his home health aide
reported that he was having trouble walking yesterday and had
several bouts of diarrhea. What is the medication that is most
likely to be causing this episode that was prescribed by the
patient’s psychiatrist?
a. Haloperidol
b. Valproic acid
c. Ziprasidone
d. Paroxetine
e. Lithium
2. A patient with chronic schizophrenia is brought to the emergency

department by her brother. The patient’s brother says he found
her on the bathroom floor with an empty pill bottle next to her. On
examination, the patient is noted to have a fever, confusion,
tachycardia, dry mouth, urinary retention, and dilated and
unresponsive pupils. Which of the following medications did the
patient most likely overdose on?
a. Fluoxetine
b. Haloperidol
c. Benztropine
d. Diazepam
e. Hydrocodone
3. One of your most chronically ill patients with schizophrenia with

marked symptoms of paranoia presents to your office after being
discharged from a psychiatric hospital 1 week ago for command
auditory hallucinations urging him to burn his own hands. During
the hospitalization, he was started on an atypical antipsychotic
medication that requires weekly blood monitoring. During your
interview, the patient mentions that he has developed a sore
throat, fever, and productive cough over the past 2 days. You
immediately order a complete blood count and differential. Which
of the following side effects of this medication is most
concerning?
a. Leukocytosis
b. Neutropenia
c. Macrocytic anemia
d. Polycythemia
e. Thrombocytopenia
4. A 46-year-old male truck driver with a history of smoking,

hypertension, type 2 diabetes, and chronic back pain is admitted
to the neurology service after having an ischemic stroke affecting
the left middle cerebral artery. He is unable to provide a list of his
home medications. Although initially cooperative, the nursing staff
report mild irritability and anxiety about 12 hours after admission.
Forty-eight hours after admission, the patient is highly agitated,
trying to pull out lines and get out of bed, necessitating the use of
mechanical restraints. You are asked to assess him urgently. On
examination, he has mild right-sided weakness, dysphasia, and a
right-sided Babinski reflex. He appears anxious with gooseflesh,
yawning, and rhinorrhea; pulse is 120 beats per minute; and his
pupils appear symmetrically dilated. You suspect that the patient
is withdrawing from which of the following substances?
a. Oxycodone
b. Alcohol
c. Alprazolam
d. Amphetamine
e. Cocaine
5. A 6-year-old child presents with a 3-year history of disruptive

behaviors at home and school. His parents report that he also has
difficulty paying attention and completing tasks. The parents also
bring teacher reports indicating that the child is having similar
problems at school. The child has had psychological testing that
demonstrates an above-average IQ and no evidence of a learning
disability. What is the child’s most likely diagnosis?
a. Schizophrenia
b. Attention-deficit hyperactivity disorder
c. Tourette’s disorder
d. Separation anxiety disorder
e. Autism spectrum disorder
6. A 24-year-old graduate student presents with severe depressed

mood of several months in duration. She reports that this is the
worst her depression has ever been. She says that she sleeps “all
the time” and that her mood is much worse in the morning,
improving later in the day. She also has lost interest in usual
activities, has “no energy,” and can’t concentrate. She is
struggling intermittently with feeling suicidal. She denies having
prior episodes like this but does admit that she has had times
when she has a lot of energy and doesn’t need much sleep.
During these times, she sometimes overspends on credit cards or
suddenly embarks on a trip. She has sometimes thought that she
was destined to be the savior of the world when she has felt this
way for a few weeks. What is the most likely diagnosis?
a. Major depression with psychotic features
b. Bipolar disorder, type II, most recent episode depressed
c. Bipolar disorder, type I, most recent episode manic
d. Major depression without psychotic features
e. Bipolar disorder, type I, most recent episode depressed
7. A 41-year-old woman is hospitalized and assigned to your

inpatient service after telling a therapist at a local mental health
center that a voice was telling her to stab herself in the chest. She
had resisted the voice for several days but felt that she was now
planning to act on this command hallucination and had chosen a
knife to stab herself with the night before presenting. She reports
to you that she has trouble concentrating and was diagnosed with
attention-deficit disorder as a child. For the past 15 years, though,
she has had recurrent bouts of depression, paranoia, and
auditory hallucinations. Even when her depression is absent and
her mood feels normal, she still hears voices and sometimes is
paranoid. What is the most appropriate medication to treat her
current episode?
a. Vortioxetine
b. Olanzapine
c. Dextroamphetamine
d. Lithium
e. Clomipramine
8. A 16-year-old boy is brought to the emergency room by his

concerned family. They report that he returned from summer
camp 1 week ago and has not been his “usual self” since then.
He talks incessantly about expecting to be announced the
valedictorian at his high school this year (despite a history of
averaging D grades) and his plans to become a world-renowned
NASA scientist. He has been spending his parents’ money on
bags of brightly colored clothes that are too large for him, is
sleeping less than 2 hours per night, and is eating very little, yet
he remains highly energetic during the day. You order an
appropriate medical workup that excludes an organic basis for his
presentation. Which of the following medications would be of
most benefit to this patient?
a. Buspirone
b. Vilazodone
c. Liothyronine
d. Lithium
e. Phenelzine
9. A 28-year-old single man with no past medical history presents to

the emergency room complaining of left-sided chest pain for the
past 2 hours that is described as a “crushing” sensation,
associated with nausea, profuse diaphoresis, and anxiety. He
denies all risk factors for cardiac disease. You admit him to the
cardiac care unit for serial cardiac enzymes and EKGs, which are
consistent with a minor anterior myocardial infarct. The next
morning, you are called by the nursing staff because the patient is
irritable and requesting to leave the hospital against medical
advice. The nursing staff informs you that he has been fatigued
since admission, has appeared tearful and depressed, and has
been complaining of headaches and consuming double helpings
of his meal trays. You order a urine drug screen and find it is
positive for which of the following substances?
a. Alcohol
b. Alprazolam
c. Cocaine
d. Clonazepam
e. Morphine
10. A 20-year-old single female patient is flown by air ambulance to

your teaching hospital with altered mental state. She was found in
bed early this morning by her mother with an empty bottle of her
prescription amitriptyline at her bedside. Her mother reports that
she only had the prescription refilled yesterday, so she believes
that the patient must have taken 30 × 50 mg tablets. You
recommend admission to the medical intensive care unit for
monitoring for which of the following complications?
a. Hyperkalemia
b. Arrhythmia
c. Hyperpyrexia
d. Hypertension
e. Hyponatremia
11. A psychiatric consult is ordered on an 83-year-old patient with a

history of chronic obstructive pulmonary disease (COPD),
hypertension, and diabetes mellitus who was admitted to the
hospital for fever and change in mental status. On examination,
the patient is sleepy and difficult to arouse. When she does
awaken, she tells you that she is at “home” and that the year is
“1956.” You speak to her family members who state that she has
gotten progressively more confused over the last 2 to 3 days. The
family says that she’s normally “sharp as a tack” and lives
independently in her own apartment. They visit with her almost
daily at home. You suspect the woman is suffering from a delirium
and order appropriate laboratory and diagnostic studies to
evaluate for medical causes of the delirium. While you await the
results of your delirium workup, which of the following is the best
recommendation for the management of delirium in this medically
hospitalized patient?
a. Minimize visitation by the patient’s family members
b. Put the patient in a room with another patient with delirium
c. Remove all of the patient’s personal items brought from home
to avoid confusion
d. Provide the patient with orienting cues such as names, clocks,
and calendars
e. Give the patient benzodiazepines every 6 hours
12. A 48-year-old woman was the driver in a fatal motor vehicle

accident 10 years ago in which the passenger in her car was
killed. She was hospitalized for 3 months and spent the first week
in a coma. Today she and her husband go to see a new
psychiatrist for management of her chronic depressive symptoms.
During the initial evaluation, the psychiatrist asks the woman
whether she has ever been involved in any traumatic events. Her
husband is surprised to hear her deny any past trauma. He
questions her about it. She responds to his questions with fluent
speech but has no recollection of the motor vehicle accident or
hospitalization. The following day, the husband asks his wife
about her past motor vehicle accident, and she is able to recall all
the details. This woman most likely fits criteria for which of the
following disorders?
a. Posttraumatic stress disorder (PTSD)
b. Dissociative identity disorder
c. Depersonalization disorder
d. Seizure disorder
e. Dissociative amnesia
13. An 85-year-old woman is seen in the emergency room after being

brought there by elder services in her town. She had been living
alone in an apartment. Neighbors complained about a terrible
smell emanating from her apartment that got progressively worse
over a year-long period. When elder services were called, it took
them a few days to get into the apartment, where they found her
crouched sitting in the bathroom tub in the dark. Her apartment
was squalid with cat feces and urine as well as dried and
decaying pet and human food everywhere. Her personal hygiene
was appalling with greasy, matted hair and filthy clothing that
smelled of urine. After receiving a shower and a careful medical
examination, she reveals a belief that her neighbors are all
involved in a “drug and sex ring.” A mental status examination
reveals a Mini–Mental Status Examination score of 18/24. She
also has marked difficulty with the Luria maneuver. MRI of the
brain reveals diffuse cortical atrophy. She also has difficulty with
word finding and maintaining set. What is the most likely
diagnosis?
a. Major depression
b. Schizophrenia
c. Delusional disorder
d. Social phobia
e. Major neurocognitive disorder due to Alzheimer’s disease
14. After careful monitoring for 24 hours, a female patient who was
admitted for an overdose is considered medically stable. You are
asked to assess her psychiatrically for a possible suicide attempt.
You proceed to take a detailed history. During your interview, the
patient does not meet criteria for major depressive disorder.
However, you note that she describes problems of a more chronic
nature, including multiple brief relationships with boyfriends who
her mother considers “unsuitable.” The patient reports that her
relationships typically start off as “wonderful” but she often finds
herself “hating” her boyfriends after several weeks and the
relationships typically disintegrate into rage and physical violence.
She reports a chronic sense of emptiness, sadness, and lack of
purpose. She describes difficulty controlling her emotions and has
abused multiple different drugs and engaged in self-mutilation by
cutting to relieve “emotional stress.” She tells you that her
overdose was an impulsive suicide attempt in response to her
mother threatening to kick her out of the house for continuing to
see her current boyfriend who is in jail. She also reports repeated
overdoses in the past when under stress. You suspect the
presence of which of the following personality disorders?
a. Antisocial personality disorder
b. Borderline personality disorder
c. Avoidant personality disorder
d. Dependent personality disorder
e. Schizoid personality disorder
15. Following inpatient psychiatric hospitalization for safety and

stabilization, a patient with borderline personality disorder is
referred to an outpatient psychotherapist for continued mental
health care. After taking a careful history, the psychotherapist
formulates a treatment plan. Which of the following
psychotherapy modalities has the strongest evidence base in the
treatment of this patient?
a. Dialectical behavioral therapy (DBT)
b. Crisis intervention
c. Family therapy
d. Interpersonal psychotherapy
e. Psychodynamic psychotherapy
16. A 27-year-old man is admitted to the surgical intensive care unit

of your hospital following a motor vehicle accident involving
ejection from a vehicle with long-bone trauma but with only minor
head laceration and with no loss of consciousness. After about 48
hours in the ICU, the patient becomes increasingly agitated and
confused. He is specifically noted to have a disrupted sleep–wake
cycle and is awake all night and much of the day. He is
disoriented to time, place, and person. He complains of seeing
bugs. On examination, he does not remember meeting you just a
few minutes earlier and has great difficulty maintaining attention
to your conversation. At times he appears to fall asleep mid-
sentence. A repeat brain MRI and CT are read as normal. Vital
signs show hypertension with blood pressure of 170/90,
tachycardia with heart rate ranging from 90 to 110, temperature of
98.7°F, and oxygen saturation via pulse oximetry at 98% on room
air. Laboratory tests including complete blood count and
metabolic panel show normal white blood cell count, normal
platelets, mild anemia with hematocrit of 35, normal electrolytes,
and normal blood urea nitrogen and creatinine. Liver enzymes
and ammonia level are also normal. What psychiatric
complication has this patient developed?
a. Dementia
b. Depression
c. Delirium
d. Dissociative identity disorder
e. Schizophrenia
17. Among the following choices, what is the most likely cause of the
patient’s delirium in the previous question?
a. Opiate intoxication
b. Alcohol withdrawal
c. Cocaine withdrawal
d. Sleep apnea
e. Anemia
18. While on call, you are asked to admit a patient who is acutely
manic. You ask her how she came to be in the hospital. She
replies, “How, now. Now we’re in the hospital. The hospital is on
the hill. Hills and peaks and valleys. The valley’s where the
waters flow. Flowing deep down below.” What impairment in
thought process is this patient manifesting?
a. Circumstantiality
b. Poverty
c. Tangentiality
d. Flight of ideas
e. Word salad
19. A 25-year-old man is admitted to an inpatient psychiatric unit

after threatening to beat up his mother, with whom he lives. His
family members brought him to the emergency department and
he agreed to come into the hospital. He reported that he had
been hearing voices telling him to beat up his mother. He
believed she was trying to poison him. After 1 day in the hospital,
he demands to leave. Which of the following facts led the resident
on call to justify involuntary commitment?
a. The patient says he will not take his medication at home.
b. The patient’s mother cannot handle him at home.
c. The patient’s psychotic symptoms have not resolved.
d. The patient refuses a follow-up appointment.
e. The patient continues to threaten his mother.
20. A 25-year-old woman became sad after a romantic breakup. For

the past 6 weeks, she has noticed intense fatigue, feeling as if her
limbs are heavy or leaden, increased need for sleep, and
increased appetite. She reports that all she wanted to do was stay
in bed and eat junk food. Her mood greatly improved when she
shared a text with her former partner and became optimistic that
the relationship might be restored. What is the most likely
diagnosis for this patient?
a. Borderline personality disorder
b. Major depression with atypical features
c. Bipolar disorder with rapid cycling
d. Seasonal affective disorder
e. Chronic fatigue syndrome
21. An 81-year-old man discusses with his therapist his past

accomplishments, including his successes in his family life,
occupational life, and civic life. He reports a sense of satisfaction
that his life has been productive and worthwhile. According to Erik
Erikson, this patient has successfully managed the psychosocial
task of developing which of the following?
a. Integrity
b. Basic trust
c. Generativity
d. Intimacy
e. Industry
22. A 24-year-old single woman develops severe depression in the

context of her parents’ insistence that she stop seeing her
boyfriend and agree to marry a man from the same cultural
background as her parents. She is sad, unable to care for herself,
and has suicidal ideation. You admit her to the psychiatric
hospital and start her on escitalopram. Despite your best efforts,
she continues to clinically decline. She develops psychomotor
retardation and nihilistic delusions, believes she deserves to be
dead, and consequently stops consuming food and drink. Her
serum urea and urine specific gravity start to rise. Which of the
following treatment options is the best choice at this time?
a. Augment with liothyronine
b. Augment with quetiapine fumarate
c. Switch to a monoamine oxidase inhibitor
d. Switch to a tricyclic antidepressant
e. Electroconvulsive therapy (ECT)
23. A friend of yours who is a 32-year-old male African American

business executive is undergoing psychotherapy to treat his
severe fear of flying. During his first session, he tells you his
therapist asked him to look at a series of photographs of
airplanes. Next week, she asked him to view a video of a flying
airplane. During their next session later this week, his therapist is
planning to take him to the local airport to watch planes departing
and landing. What is the name of this type of therapy?
a. Biofeedback
b. Exposure therapy
c. Cognitive-behavioral therapy
d. Psychodynamic therapy
e. Supportive therapy
24. You decide to proceed with electroconvulsive therapy (ECT) on a

24-year-old female patient with severe depression who is not
responding to antidepressants. You discuss your plan with the
patient’s mother in her capacity as the patient’s substitute
decision maker. Her mother is very concerned about your
recommendation for “electric shock treatment” for her daughter.
With significant education on the risks, benefits, and alternatives
to your treatment plan, she eventually agrees but asks you to
minimize her daughter’s risk of adverse effects from the
treatment. Which of the following factors reduces the risk of
complications from ECT?
a. Antipsychotics
b. Benzodiazepines
c. Unilateral electrode placement
d. Intravenous caffeine
e. Older age
25. You are the psychiatry resident on an inpatient mood disorders

unit. A 40-year-old single male patient with a well-established
history of bipolar disorder type I is admitted in an acutely manic
state. He has prominent hyperreligious delusions that have
caused concern to his sister, who has observed him in various
locations around the house prostrated, intensely in prayer, and
muttering Bible verses. He is started on an antipsychotic agent.
Two days later, when you arrive for morning rounds, you observe
him to be completely still and mute, kneeling in a praying stance
in front of your interview room. You proceed to perform a full
neurologic examination. You find that you can move his arms into
any position and he will maintain the pose. As you test his muscle
strength, the further you flex his forearms, the more he resists
you. You then ask him to “stick out your tongue so that I can put a
pin in it,” and he obeys your command. What is this patient
displaying?
a. Cataplexy
b. Catatonia
c. Delirium
d. Malingering
e. A switch to depression
26. You are concerned about the development of catatonia in the

patient described in the preceding question and discuss your
findings with the attending psychiatrist. Together you determine
that a change in management is indicated. Which of the following
classes of medication is the best treatment option at this time?
a. Alpha-adrenergic agonist
b. Antidepressant
c. Cholinesterase inhibitor
d. Benzodiazepine
e. Mood stabilizer
27. A 71-year-old man presents to his physician complaining of

balance problems and stiffness in his body. He says it feels like
he can’t move as fast as he used to. His wife reports that he has
less facial expression, and she has also noticed that his
handwriting has gotten smaller. While in the office, the physician
notices an involuntary trembling of the patient’s hands. The
physician suspects that the patient has Parkinson’s disease. If the
patient was to develop psychotic symptoms, which of the
following antipsychotic medications would be the best choice to
avoid worsening motor symptoms in this patient?
a. Perphenazine
b. Haloperidol
c. Fluphenazine
d. Chlorpromazine
e. Clozapine
28. A 29-year-old postdoctoral student has been seeing you weekly

for individual psychotherapy in the student health clinic for the
past 6 months. He carries the diagnosis of mild depression, which
is exacerbated by social isolation following immigration to the
United States and has significant paranoid personality traits.
During one session, he reveals that he has developed romantic
feelings for a 22-year-old undergraduate student named Donna,
who is residing in the neighboring dormitory. During the next
session, he tells you that he has researched the college website
and found out that Donna is from Dayton, Ohio and is majoring in
economics. The next week he reveals that he has been observing
Donna and proceeds to give you a detailed description of the
structure of her day. Today the patient presents to your session
and appears highly agitated. He tells you that he asked Donna
out on a date to the movies yesterday but she refused. He feels
spurned and extremely angry and admits that he has had
fantasies about hurting her. He also reveals that he is now
carrying a knife in his pocket “just in case” he sees her again. You
realize that you are legally bound to warn or protect Donna under
which of the following constructs?
a. Duty
b. The Health Insurance Portability and Accountability Act
(HIPAA)
c. Incapacity
d. M’Naghten
e. Tarasoff
29. A psychiatrist is cross-tapering a patient off clomipramine and

starting phenelzine to treat his refractory major depression.
During the cross-taper over several weeks, the patient begins to
experience delirium, tremor, diaphoresis, rigidity, hyperpyrexia,
and myoclonus. A family member brings him to the emergency
room. What is his most likely diagnosis?
a. Neuroleptic malignant syndrome
b. Serotonin syndrome
c. SSRI discontinuation syndrome
d. Monoamine oxidase inhibitor–tyramine reaction
e. Stevens–Johnson syndrome
30. A 28-year-old man sees a psychiatrist for treatment of

schizophrenia. He reports that in the past, he was treated with the
atypical antipsychotic risperidone for over a year. The medication
was discontinued when he developed galactorrhea. Antipsychotic
drugs elevate prolactin due to which of the following
mechanisms?
a. Dopamine is a competitive inhibitor of prolactin.
b. Antipsychotics bind to prolactin receptors causing blockade.
c. Prolactin is under tonic inhibitory control by dopamine.
d. Antipsychotics stimulate the pituitary gland to produce
prolactin.
e. Antipsychotics simulate production of prolactin precursors.
31. You are an outpatient psychiatrist. A 42-year-old female patient

with a long history of paranoid-type schizophrenia has
experienced significant weight gain and type 2 diabetes mellitus
on her current atypical antipsychotic medication, olanzapine. She
repeatedly asks you to change her medication to one that is
associated with less weight gain. After significant counseling on
the risks and benefits of available options to help her lose weight,
you agree to switch her medication to arapiprazole, an alternative
atypical antipsychotic. Three days after completing the switch,
she presents as a walk in to your outpatient psychiatry clinic and
tells the receptionist that she has to see you because she “cannot
live like this anymore.” You see her urgently. She appears to be
agitated and restless and initially paces around the room. When
you offer her a chair, she sits down but constantly changes
position. She reports that she has a constant, irresistible urge to
move that is preventing her from carrying out basic activities or
being able to sleep. She is constantly uncomfortable to the point
that she has even been considering suicide unless the situation
improves. On examination, the patient denies psychotic
symptoms but is very anxious. Which of the following movement
disorders is this patient experiencing?
a. Chorea
b. Dystonia
c. Parkinsonism
d. Akathisia
e. Tardive dyskinesia
32. A 40-year-old married female nurse is admitted to the neurology

service for peripheral numbness, tingling, and weakness that
started 1 week after recovering from the flu. Physical examination
is not consistent with a known anatomic lesion. An extensive
workup for Guillain–Barré’s syndrome including routine labs, MRI
and MRA, and lumbar puncture is unremarkable. However, the
patient remains convinced that she has Guillain–Barré’s
syndrome, remains bedbound, and is not participating in physical
therapy. A psychiatry consult is placed. You obtain psychosocial
history from the patient’s husband who reports that his wife has
always found it hard to verbalize emotions and was brought up in
a household where her mother was frequently restricted to bed
due to recurrent bouts of abdominal pain. About 1 week before
contracting the flu, she started a new job as the manager of a
nursing home. This has been extremely stressful because the
patient has been on call 7 days a week, resulting in being woken
up an average of three times every night. Her husband has been
encouraging her to seek alternative employment, but she has
resisted his discussions. The patient’s presentation is consistent
with which of the following psychiatric disorders?
a. Histrionic personality disorder
b. Conversion disorder (functional neurologic symptom disorder)
c. Major depressive disorder
d. Malingering
e. Somatic symptom disorder
33. A 39-year-old married Caucasian woman is being treated for

major depressive disorder in an outpatient psychiatry clinic. After
failing three different antidepressant medications, she is started
on a new antidepressant. A week later, her husband takes her out
to her favorite French restaurant to celebrate their anniversary.
She orders onion soup, Chianti wine, roast duck in orange sauce,
and chocolate mousse. Halfway through the meal, she starts to
complain of a dull headache. By the end of the meal, she
complains of a severe occipital headache. Her husband notices
that her pupils are dilated and she is sweating profusely, and he
calls for an ambulance. The patient is subsequently admitted to
the intensive care unit to treat her severely elevated blood
pressure. Which of the following medications is most likely to
have caused this adverse effect?
a. Phenelzine
b. Bupropion
c. Fluoxetine
d. Sertraline
e. Venlafaxine
34. Following medical stabilization, the patient described in the

previous question is discharged from the hospital. After further
discussion of risks and benefits with her psychiatrist, she elects to
continue on her antidepressant medication due to its efficacy.
One month later, the patient consults an outpatient neurologist for
recurrent headaches. After further investigations, she is
diagnosed with migraines and prescribed sumatriptan as abortive
therapy. One week later, after taking sumatriptan three times
during the same day, she abruptly develops diarrhea and
vomiting, fever, shivering, and tremor. Her concerned husband
drives her to the local emergency room. By the time she arrives,
she is restless and disoriented to time and place. She exhibits
marked hyperreflexia on neurologic examination. Which of the
following complications has this patient developed?
a. Drug allergy
b. Hypertensive crisis
c. Serotonin syndrome
d. Neuroleptic malignant syndrome
e. Seizure disorder
35. A 30-year-old married Caucasian man is referred to your

outpatient psychiatry clinic by his primary care practitioner, who
has been concerned that the patient appears depressed and
inattentive during their interviews. You proceed to take a detailed
history and note that the patient has no past psychiatric history or
family history of psychiatric disease. He does not take
medications or use drugs or excess alcohol. He does not endorse
criteria for major depressive disorder, but you are struck by his
difficulty in attending to the interview and his slow responses to
your questions. In the middle of the interview, he falls asleep in
his chair but wakes immediately when you call his name. He
reports excessive drowsiness during the day and complains of
dropping objects he is holding when he laughs or cries. He also
complains of vivid “visions of my dead grandmother” when he is
about to fall asleep at night. The patient’s wife states that he does
not snore loudly at night, and he scores 30/30 on the Mini–Mental
Status Examination. You suspect which of the following
diagnoses?
a. Obstructive sleep apnea hypopnea
b. Narcolepsy
c. Nightmare disorder
d. Hypersomnolence disorder
e. Substance/medication-induced sleep disorder
36. A 10-year-old child has an annual checkup. The child reports that
she has started collecting key chains, an interest that she shares
with her mother and friends. She is very excited because she is
the only one of her friends who has collected over 20 key chains.
The child states that things are okay at home and school. Her
parents report that she is doing well, although they would like her
grades to be higher. According to Erikson, which of the following
developmental tasks is most relevant for this child?
a. Initiative versus guilt
b. Identity versus role confusion
c. Generativity versus stagnation
d. Industry versus inferiority
e. Ego integrity versus despair
37. A 39-year-old patient presents with a complaint of depression. He

has a 4-year history of subtle changes in his personality including
emotional lability, impulsive outbursts, obsessionality, and even
hostility. He recently lost his job because he was increasingly
disorganized and working too slowly. He appears withdrawn and
restless. On examination, he has increased eye blinking, mild
bradykinesia, and mild hyperreflexia. The patient’s father had the
onset of dementia at age 37 and died of severe dementia at age
55. What is the patient’s most likely diagnosis?
a. Major neurocognitive disorder due to Huntington’s disease
b. Major neurocognitive disorder due to Parkinson’s disease
c. Major frontotemporal neurocognitive disorder
d. Early-onset major neurocognitive disorder due to Alzheimer’s
disease
e. Creutzfeldt–Jakob’s disease
38. A 25-year-old woman with a history of insulin-dependent diabetes

mellitus is admitted to the trauma service after sustaining blunt
abdominal injuries during a motor vehicle accident. She recalls
driving in town with her 3-year-old son before becoming
lightheaded, losing control of her vehicle, and swerving into the
path of oncoming traffic. Paramedics recorded her blood sugar as
30 at the scene. Tragically, her son was severely injured and is in
critical condition in the children’s hospital. A psychiatry consult is
scheduled due to the patient’s shock on learning about her son’s
condition. On evaluation, she reports no past psychiatric history.
However, since the accident, she has developed severe anxiety,
insomnia due to daily vivid nightmares about the accident, a
strong startle response, a fear of driving, sense of shortened and
uncertain future, and intrusive memories of the accident at least
four times daily. She denies suicidal ideation. You offer the
patient brief counseling and recommend ongoing therapeutic
monitoring for which of the following psychiatric disorders?
a. Adjustment disorder
c. Posttraumatic stress disorder
d. Panic disorder
e. Polysubstance abuse
39. You have been treating a 29-year-old single male patient with
obsessive-compulsive disorder with high-dose fluvoxamine for 15
weeks in your outpatient psychiatry practice. Unfortunately he has
experienced little improvement in the frequency of his obsessions
regarding contamination with germs and continues to wash his
hands approximately 20 times per day. You discuss the options of
changing medication and/or augmenting with psychotherapy.
Although the patient expresses interest in psychotherapy, he tells
you he in unable to find adequate time to participate because he
is working intensely to avoid the bankruptcy of his nursery
business. He requests switching to an alternate medication. After
counseling the patient about the risks and benefits of the new
medication, you taper him off fluvoxamine and onto the new
medication, which you gradually increase in dose. Two weeks
after starting the new medication, the patient schedules an early
appointment to see you because he is experiencing a variety of
distressing side effects including dry mouth, blurred vision,
difficulty with urination, feeling his thinking is “foggy,” and
lightheadedness when he stands up from a seated or lying
position. These side effects have occurred because the new
medication belongs to which of the following drug classes?
a. Monoamine oxidase inhibitor (MAOI)
b. Tricyclic antidepressant (TCA)
c. Norepinephrine–dopamine reuptake inhibitor
d. Selective serotonin reuptake inhibitor (SSRI)
e. Typical antipsychotic
40. A 60-year-old Caucasian man presents to your outpatient

psychiatry clinic reporting that he is an alcoholic. He states that
he is desperate to “kick the habit once and for all” for the sake of
maintaining his relationship with his current girlfriend who is
threatening to leave him if he continues to drink. Further interview
reveals a chronic pattern of clinical impairment including multiple
job losses for intoxication, three divorces, and legal charges for
driving under the influence due to multiple relapses on alcohol.
The patient was recently consuming 12 beers per day but
completed an inpatient detoxification program 1 week ago.
Although he has managed to maintain his sobriety since then, he
reports vivid dreams about consuming alcohol and is
experiencing frequent cravings in response to cues such as
walking past a local bar close to work that he used to frequent at
lunch time. The patient does not meet criteria for another
diagnosis other than alcohol use disorder in early full remission.
You strongly recommend attending 90 Alcoholics Anonymous
(AA) meetings in 90 days. You also start which of the following
medications to reduce his chance of relapse and to curb the
quantity of alcohol ingested if he does relapse?
a. Buprenorphine
b. Clonidine
c. Naltrexone
d. Memantine
e. Quetiapine
41. A 21-year-old man is admitted to the psychiatric hospital after

contemplating suicide. On interview, he reports no prior history of
mental illness or substance use. He states that he began thinking
of suicide 3 weeks ago after being arrested for having sex with a
17-year-old who was not at the legal age of consent in his state. If
convicted, in addition to possible prison time, he will be required
to register as a sex offender. He feels humiliated and despondent.
You inquire about further neurovegetative symptoms. In addition
to increased suicidality, for the past 3 weeks, the patient reports
impaired sleep with early morning awakenings, decreased
energy, lack of interest in life, feelings of intense sadness, and
guilt. What is the most likely diagnosis at this point?
a. Chronic depressive disorder (dysthymia)
b. Pedophilia
c. Manic episode
d. Insomnia disorder
e. Major depressive episode
42. A 19-year-old college freshman is brought to see you at the

university health services clinic after hours. His roommates report
that he has been withdrawn and uncharacteristically avoidant with
decreased participation in activities and a decline in grooming and
bathing for the past 2 months. In the past 2 weeks, he has not
been sleeping well and has been saying bizarre things to them.
When you enter the room to see him, he is sitting in the corner
looking afraid. He says, “I know you are with the CIA.” When you
say that you are a doctor, he says, “Then you are the one who
implanted that eavesdropping device in my brain!” After speaking
with you some more, he reveals that he has been receiving
communications in the form of color-coded messages from the
CIA over his smart phone. In addition, he has been hearing clear
voices telling him to “be careful” when no one else is in the room
with him. With his permission, you call his family who report that
this behavior is all new and that, when they took him to college 4
months ago, he was well. His urine drug screen is negative for
drugs, and he and his friends deny that he has had any
hallucinogenic or other drug experimentation. What is the most
likely diagnosis?
a. Schizophrenia
b. Schizophreniform disorder
c. Bipolar disorder
d. Schizotypal personality disorder
e. Panic disorder
43. An 18-year-old man has been newly diagnosed with

schizophrenia. He was admitted to the inpatient psychiatry ward
and started on the atypical antipsychotic olanzapine. One month
later, you see him in your outpatient psychiatry clinic for routine
follow-up. He reports that his psychiatric symptoms are under
good management but complains that he has gained 10 pounds
in weight since discharge from the hospital. You weigh the patient
and request laboratory tests. You find that total cholesterol is
elevated at 262, LDL cholesterol is elevated at 180, triglycerides
are elevated at 250, and high-density lipoprotein (HDL)
cholesterol is low at 20. Before the patient’s psychiatric
hospitalization, you note that his lipid profile was within normal
limits. Which other medical condition is the patient at risk of
developing?
a. Diabetes insipidus
b. Cataracts
c. Diabetes mellitus
d. Hypothyroidism
e. Leukopenia
44. A 39-year-old patient tells you that he believes his mother has
been mentally ill for many years, but she has never sought
treatment. He tells you about an incident when his mother
became convinced that the new neighbor who moved in across
the street was in love with her. She had never spoken to the man,
but she began to follow him around and spy on him. After a
couple of months, he called the police, and she was found guilty
of stalking in a court of law. Her belief that this man was in love
with her would be categorized as what type of delusion?
a. Grandiose
b. Jealous
c. Somatic
d. Erotomanic
e. Persecutory
45. You are the psychiatry resident on the inpatient psychotic
disorders unit of a busy teaching hospital. While on call, you are
asked to urgently assess a 32-year-old African American male
patient who was admitted 2 days ago in an agitated state
following an altercation with his mother. On examination, the
patient appears acutely distressed, he is looking upward, and is
unable to follow your finger when you attempt to test his eye
movements. Vital signs are stable but for sinus tachycardia of 100
beats per minute. Briefly reviewing his chart, you note that the
patient has been diagnosed with psychotic disorder not otherwise
specified, has no prior history of treatment with psychotropic
medications, and has recently been started on scheduled
haloperidol 5 mg by mouth twice per day. In addition, the patient
has received up to three 5-mg doses of haloperidol per day for
acute agitation since admission. Coadministering haloperidol with
which of the following classes of medication might have
prevented this reaction?
a. α-2 adrenergic antagonist
b. Anticholinergic agent
c. β-Adrenergic antagonist
d. Cholinesterase inhibitor
e. Selective serotonin reuptake inhibitor
46. A 50-year-old single female patient with schizoaffective disorder

lives independently in an apartment with the assistance of case
management services. She was recently switched to a new
antipsychotic medication with rapid dosage titration by her
outpatient psychiatrist. A few days later, her air conditioner quit
working during the summertime, when the maximum ambient
temperature was approximately 101°F. The patient’s case
manager paid her a home visit after the patient failed to answer
the telephone. The case manager let herself into the apartment
when the patient failed to answer the door and was shocked to
find the patient lying face down on the living room floor. Although
the patient opened her eyes when the case manager shook her
gently, she did not respond to any questions. The patient
appeared febrile, sweating, and rigid, and the case manager
telephoned immediately for an ambulance. During the patient’s
subsequent hospitalization in the ICU, which of the following
laboratory values was most likely to be grossly elevated?
a. Creatine kinase
b. Glucose
c. INR
d. LDL cholesterol
e. Platelet count
47. A 45-year-old male patient with a long history of schizophrenia is

involuntarily committed to the state psychiatric hospital because
he is experiencing command auditory hallucinations urging him to
kill his mother, who he believes is an agent of the devil. When you
assess him in your capacity as the on-call attending psychiatrist,
you recommend a treatment plan in which you suggest starting
back on an antipsychotic medication. The patient refuses
medication, angrily stating that he does not have a mental illness.
Which of the following aspects of capacity is the patient unable to
demonstrate?
a. Appreciating the nature of his illness
b. Communicating a choice
c. Deciding on a choice
d. Reasoning about treatment options
e. Understanding the information you have communicated
48. A 48-year-old woman who lives in a state-supported group home

presents to the emergency department after having a witnessed
grand mal seizure shortly after dinner. She is lethargic and
disoriented on arrival and gradually becomes more alert during
your assessment. She tells you that she does not remember what
happened. A staff member from the group home tells you that the
patient has been under stress lately and has been drinking a
large amount of diet cola. Her medicines include clozapine 500
mg qhs, lithium 500 mg tid, glycopyrrolate 2 mg qhs, and
escitalopram 20 mg qd. Her blood pressure is elevated at 195/95
mm Hg. Her heart rate is 90 beats per minute, and her respiratory
rate is 15 breaths per minute. She does not smoke. A basic
electrolyte laboratory panel reveals a serum sodium of 119
mmol/L. Her chest radiograph is normal. What is the most likely
diagnosis?
a. Syndrome of inappropriate antidiuretic hormone secretion
b. Clozapine toxicity
c. Hypertensive encephalopathy
d. Primary polydipsia
e. Serotonin syndrome
49. You are asked by the nurse at your clinic to conduct a home visit
on a reclusive 47-year-old woman who has been unable to come
in for an appointment for the last 3 years. Her daughter agrees to
meet you at the home the next morning. She shows you into the
house where you find the patient sitting in a house dress in a
reclining chair in her living room. She tells you that she has not
left the house in 3 years “because it is too scary out there,”
gesturing toward the street. You ask more about what happened
3 years ago. She recounts that she was out at a shopping center
when she suddenly had the abrupt onset of a severe wave of
anxiety. It lasted approximately 15 minutes but caused her to run
out of the mall and back to the safety of her car. Since then, she
has had many more such attacks. She has refused to leave her
home for the last 21/2 years. She says that she likes having
people visit her, but she just can’t bring herself to go out again.
She has the attacks sometimes at home and has not sought
treatment for them. She said that the same thing happened to her
mother, and she spent the rest of her life at home. She asks you if
you understand what is going on with her and if you can fix it. You
tell her that you have seen this before and can recommend the
right kinds of treatment. The primary condition is:
a. Major depression
b. Panic disorder
c. Generalized anxiety disorder
d. Arachnophobia
e. Obsessive-compulsive disorder
50. A 9-year-old boy is brought into the emergency department by his

distraught parents after he tried to attack his mother with a
kitchen knife. His mother was unharmed, but the parents called
the police who suggested an emergency evaluation after
observing the boy’s demeanor. He was verbally aggressive and
pacing, talking loudly, and swearing. The police escorted them to
the emergency department where the boy was restrained and
medicated acutely with a combination of emergency sedatives.
The parents explain to you that their son seemed to develop
attention-deficit disorder a few months ago and was prescribed a
dextroamphetamine-containing medication by his pediatrician. It
seemed to help at first, but then his personality began to change.
Where before he was an affable, bright, athletic boy, he became
increasingly wary, agitated, and sleepless. The situation
worsened recently when he started accusing his mother of putting
poison in his food. He attacked his mother after she made a new
dish with which he was unfamiliar. The patient’s father has bipolar
disorder. His maternal uncle has schizophrenia, and his mother
had attention-deficit/hyperactivity disorder as a child. The best
next step would be to hospitalize the patient and:
a. Start citalopram therapy
b. Start lithium therapy
c. Start aripiprazole therapy
d. Start group therapy
e. Discontinue dextroamphetamine therapy
51. A 39-year-old woman walks into the emergency department with

a broken nose. She tells you that she fell out of bed and landed
on her face. She and her husband both smell of alcohol but do
not appear intoxicated. You obtain a surgical consult, and after
the patient is evaluated, you check in with her again. Before you
enter the room, you overhear the husband speaking in a
threatening tone to his wife. He says, “You deserved it this time,
you louse!” When you enter the room, he appears startled and
she appears frightened. You suspect spousal abuse. The best
next step would be to:
a. Call the police to arrest the husband
b. Pull the husband out of the room and confront him
c. Try to separate the couple and talk to the woman alone
d. Call the patient’s home to see if anyone there knows what
happened
e. Ask the couple more about how she fell out of the bed
52. A homeless man is brought to the emergency department by the

police in response to reports that he has been wandering the
streets in a confused state. On examination, he appears
disheveled and smells faintly of alcohol. He does not exhibit
nystagmus or ataxia. On the Mini–Mental State Examination, he
is not oriented to time, place, or person. He is very talkative with
marked anterograde amnesia and makes a variety of flamboyant
and widely varying claims about how he came to be in the
emergency department today, including meeting with an old
drinking buddy in the residents’ quarters. This presentation is
caused by deficiency of which of the following vitamins?
a. B12
b. Folate
c. Niacin
d. Thiamine
e. Vitamin E
53. A 53-year-old married woman presents to your primary care clinic

accompanied by her concerned husband. He reports that she has
undergone a significant change in personality over the last 12
months. Previously, a meticulously groomed woman who was
actively involved in church and charity work, she is now exhibiting
poor hygiene and disinhibited behavior such as striking her
husband when she does “not get her own way.” With significant
embarrassment, her husband reveals that the other day, she
attempted to masturbate in public, prompting the visit to your
clinic today. There is a family history of early-onset dementia. The
patient scores 24 of 30 on Mini–Mental State Examination. Your
laboratory workup is unremarkable, but MRI of the brain reveals
significant atrophy in the frontal and anterior temporal lobes. What
is the most likely diagnosis?
a. Major neurocognitive disorder due to Alzheimer’s disease
b. Major neurocognitive disorder due to HIV infection
c. Major neurocognitive disorder due to Huntington’s disease
d. Major frontotemporal neurocognitive disorder (Pick’s disease)
e. Major vascular neurocognitive disorder
54. A 48-year-old woman is interviewed in the emergency

department after her sister brought her in because she was afraid
the patient might “do something crazy.” The sister reports that the
patient has been depressed for a very long time and has been
undergoing serious stress. She states that the patient has been
saying she would be better off dead and that life isn’t worth living.
The patient reports that she has been progressively more
depressed during the past month. She recounts a stressor of
losing her job 1 month ago because of cutbacks, but she believes
they let her go because she wasn’t performing well. In addition, 3
weeks ago, she ended a long-term romantic relationship of 5
years after a great deal of anger and turmoil. A week before
admission, she learned that her previously rent-controlled
apartment where she had lived for many years was being sold
and that she would have to move. She loves her neighborhood
but won’t be able to afford living there any longer. She reports
that she has felt seriously depressed for at least 1 month and has
had marked neurovegetative symptoms of depression. In
addition, she reports a profound sense of anhedonia and spends
her days lying in bed without eating or showering. She notes that
she is hopeless about the future and that she doesn’t believe she
will ever feel better. She is vague when directly questioned about
suicidality. You make the diagnosis of major depression, but you
are concerned about the patient’s suicide risk. The most
important risk factor for suicide in this patient is:
a. Major depression
b. Neurovegetative symptoms
c. Loss of a romantic relationship
d. Loss of her job
e. Hopelessness
55. A 39-year-old man visits a new primary care physician for a first
visit at the urging of his mother. He denies symptoms of
depression except for occasional low mood. His father died when
he was 14, and he has lived with his mother since that time. He
works as a computer programmer and says that he has many
acquaintances but few friends and no romantic relationships. His
mother had to convince him to go to the appointment because he
had trouble deciding to see a physician. His mother accompanies
him on the visit and relays that she often decides things for him
because he has “never been able to think for himself.” He says,
“People think I’m too clingy. The truth is, I just want people to care
about me.” When you speak with him alone, he appears to have a
normal intellect, no magical or odd thinking, and a stable sense of
self but reveals a desperate fear that his mother will abandon him.
He denies any self-destructive or impulsive behaviors. The most
likely diagnosis is:
b. Dependent personality disorder
c. Schizotypal personality disorder
d. Narcissistic personality disorder
e. Personality disorder
56. A 27-year-old woman is brought to the emergency department by

the local police because she has been harassing her neighbors.
Her family arrives shortly afterward and appears very concerned.
The police report states that the young woman’s apartment
manager called because she was banging on all her neighbors’
doors and screaming in the stairwell. On examining the patient’s
apartment, the police found the place to be filthy and malodorous,
with rotting garbage and food in the kitchen. The windows were
sealed and covered with dark curtains, and there were several
televisions and computers in the living room, all turned on at the
same time. The patient’s family reports that for the past year, she
has seemed increasingly odd, disassociated herself from family
activities, and gave up a well-paying job as a computer system
administrator. In addition, she had abruptly ended a long-term
romantic relationship for no particular reason. On mental status
examination, the young woman is disheveled and wearing several
layers of dirty clothes. She appears wary and guarded. Her
speech is normal in rate, volume, and production. She is
conversant and explains that she has been defending herself
against aliens who want to use her as a specimen. She believes
that she began picking up on hidden transmissions in her e-mail
at work, revealing an alien conspiracy, perhaps involving the CIA.
She states that she left her job to monitor these hidden
transmissions full time and that she has been hiding in her
apartment because they know she is on to them. She ended her
recent relationships because she felt that the aliens would harm
the people she cared about. She denies substance use or any
medical symptoms. She reports that she has been eating and
sleeping well and that her mood is good. She denies hearing
voices. Diagnostic testing, including drug screen, complete blood
count, chemistry panel, and brain MRI are all normal. The most
a. Schizophrenia
b. Bipolar disorder
c. Major depression
d. Alcohol abuse
e. Paranoid personality disorder
57. You prescribe a selective serotonin reuptake inhibitor

antidepressant for a patient suffering from major depression
requiring an inpatient psychiatric admission, and 2 days later, she
appears markedly anxious. The nursing staff is very concerned,
suggesting the patient may need additional sedation. On your
examination, the patient is agitated and pacing, bouncing her legs
up and down during your interview, and is unable to focus on the
conversation. She notes that she doesn’t know what is
happening, but that she just can’t sit still, feeling like she has to
move her legs around. The most likely diagnosis is:
a. Neuroleptic malignant syndrome
b. Medication-induced akathisia
d. Serotonin syndrome
e. Caffeine intoxication
58. A 53-year-old man admitted to the inpatient psychiatric unit for

treatment of bipolar disorder is found lying in the hallway. On
examination, he is conscious but is confused and dysarthric. The
staff reports that he has been progressively sedated and
confused for the past 24 hours. He states, “I think the doctors are
trying to kill me.” On reviewing his chart, you note that he was
admitted 1 week prior and was restarted on his usual dose of
carbamazepine because of a low level. Then, 3 days ago, he
developed an upper respiratory infection and was treated with an
antibiotic. His last carbamazepine level was measured 3 days
ago. You conduct a thorough physical and review of systems to
assure yourself that the patient did not suffer a syncopal episode
and wasn’t injured when he fell. The most likely diagnosis is:
a. Malingering
b. Dementia
c. Drug toxicity
d. Progressive upper respiratory infection
e. Normal pressure hydrocephalus
59. A 50-year-old patient with severe intellectual disability and

schizophrenia presents to the emergency room with airway
obstruction. On presentation, the patient is hypoxic. Emergency
personnel ascertain that the patient has an upper airway
obstruction and will require an emergency tracheotomy. What
would be the critical issues regarding informed consent with this
patient?
a. Providing an appropriate level of information for a patient with
intellectual disability and schizophrenia
b. Establishing capacity in a hypoxic patient with intellectual
disability and schizophrenia
c. Ensuring that the consent is voluntary
d. The patient should be committed
e. Informed consent is not necessary
60. A 30-year-old woman presents with the chief complaint that

everyone always leaves her. She has been married and divorced
three times. She states that each husband initially seemed
perfect, but she subsequently realized they were total fakes. She
reports that her parents divorced when she was 4 and that she
was raped by her stepfather numerous times from the ages of 6
to 10. She has had more than 60 sexual partners. She reports
persistent financial concerns. She expresses chronic feelings of
emptiness. During the interview, the patient is alternately
seductive and irritable. She has a history of a polysubstance
abuse but denies any recent substance abuse history. The most
appropriate treatment for this patient is:
a. Begin antipsychotic medication
b. Electroconvulsive therapy
c. Dialectical behavioral therapy
d. Inpatient psychiatric admission to a dual-diagnosis unit
e. Begin long-term psychodynamic psychotherapy
61. An 8-year-old boy is brought to your office for evaluation of

difficulties in the home and at school. His mother states that he is
very difficult to manage at home. At school, he seems to have
difficulties following instructions, frequently forgets his homework,
and often speaks out in class without having been called on. He
has had psychological testing that demonstrates an above-
average IQ and no evidence of learning disability. Which of the
following will be the most appropriate means to manage this boy?
a. Venlafaxine
b. Psychodynamic psychotherapy
c. Atomoxetine and behavioral therapy
d. Citalopram and cognitive therapy
e. Supportive psychotherapy
62. You have been called to evaluate a patient in the emergency

department. The patient had been highly combative. He has a
long history of schizoaffective disorder. The patient has been
present for three emergency ward shifts. Initially, he was
managed with several doses of intramuscular haloperidol. He
appeared to respond but then began to demonstrate agitation that
was then treated with oral olanzapine. The patient then became
increasingly agitated and received high-dose intramuscular
ziprasidone. He became delirious with unstable blood pressure
and diaphoresis, fever, rigidity, and then seizures. What is his
likely diagnosis at this time?
a. Serotonin syndrome
b. Neuroleptic malignant syndrome
c. Dystonia
d. Akathisia
e. Disulfiram-related toxicity
63. An 85-year-old woman with no prior psychiatric history is

evaluated in the emergency department for odd behavior.
According to the patient’s family, she has been awake for 2 or 3
days with constant talking and activity. On examination, the
patient is agitated, pacing the room, talking nonstop and not
allowing you to interrupt her, and appears a bit paranoid. The
most appropriate action is:
a. To treat the patient with a mood stabilizer for bipolar disorder
b. To treat the patient with synthetic thyroid hormone replacement
c. To treat the patient with an antidepressant medication
d. To order a thorough medical and neurologic workup
e. To treat the patient with an antipsychotic medication for
schizophrenia
64. A 40-year-old woman presents to your office for the first time.
She states that she has never seen a psychiatrist before, but her
friends encouraged her to make the appointment because they
are worried about her. She tells you that since her divorce 4
months ago, she has been crying all the time. She says she has
felt so down that she has rarely left her house and on some days,
she does not even get out of her pajamas. She reports she has
lost about 15 pounds because she has no appetite. She blames
herself for the failure of her marriage and feels horribly guilty
about how the failure of her marriage is affecting her children. Her
friends are concerned because she has not been joining them for
their weekly “girls’ night out.” She says she just has no desire to
do anything that she used to enjoy. She also complains of
difficulty falling asleep and says that she hasn’t felt rested in
months. You diagnose the patient as being in the midst of a major
depressive episode. Sleep studies have revealed that which of
the following sleep disturbances occur in depression:
a. Increased latency to REM
b. Increased delta sleep
c. Decreased stage 2 sleep
d. Decreased stage 4 sleep
e. Decreased time spent in REM
65. A 71-year-old woman comes to your office accompanied by her

adult daughter. This is your first meeting and you ask the
daughter to describe her mother’s personality. The daughter
reports that her mother has always paid painstaking attention to
rules, lists, and schedules. For example, she would always make
detailed “to do” lists. Her daughter states that if her mother
misplaced the list, she would spend an inordinate amount of time
looking for the list rather than just rewriting it. The daughter says
her mother always needed every detail of a project to be perfect.
She would spend weeks packing in preparation for family
vacations. She would also repeatedly and excessively clean the
family home so that “one could eat off the floor.” The daughter
states that her mother becomes very frustrated when others do
not meet her moral and ethical standards. Recently, her mother
was very angry because a teenager from the neighborhood kept
cutting through her daughter’s backyard rather than using the
sidewalk. Her daughter says, “She just can’t let it go.” She says
that her mother is “extremely stubborn” and always insists that
things be done “her way.” For example, there is one and only one
way to load the dishwasher. The mother nods her head and
concurs saying, “I have been a perfectionist all my life.” Based on
the information provided, this patient’s most likely diagnosis is:
a. Antisocial personality disorder
b. Narcissistic personality disorder
c. Obsessive-compulsive disorder
d. Schizoid personality disorder
e. Obsessive-compulsive personality disorder
66. A 22-year-old man is brought to the local emergency ward by the

police after being arrested in a grocery store for causing a
disturbance. The nature of the disturbance is unclear, but the
police indicate that the man was repeatedly accusing them of
working for the National Security Agency and having a plan to
“put me away.” On examination, the young man appears agitated,
disheveled, and frightened. He has been handcuffed to the bed
by hospital security and is straining at his restraints. His speech is
quite disorganized, and he is very upset that you wish to measure
his vital signs with the equipment in the room. He states, “You are
going to give me away.” The most likely diagnosis at this point is:
a. Panic disorder
b. Heroin intoxication
c. Attention-deficit/hyperactivity disorder
d. Schizophrenia
e. Hypothyroidism
67. You have been treating a 56-year-old woman for bipolar disorder
for the past 15 years. In reviewing your notes regarding her
clinical course over the past year, you see that you hospitalized
her for a major depressive episode 1 year ago in August. In
November last year, she had an acute manic episode requiring
another hospitalization. She was doing well in January but then
slid into another major depressive episode in February that you
were able to treat with medication as an outpatient. Just last
month in April, her husband called your office because she was
demonstrating symptoms of mania again. You realize that this
woman has had four episodes in the last 12 months that met the
criteria for either a major depressive episode or a manic episode.
What would be the correct specifier to apply to her diagnosis of
bipolar I disorder?
a. With catatonic features
b. With atypical features
c. With peripartum onset
d. With seasonal pattern
e. With rapid cycling
68. An 87-year-old woman with a history of mild mixed dementia is

admitted for confusion and a urinary tract infection. When the
nurse attempts to place a Foley catheter to improve urine
drainage, the patient becomes agitated and refuses the catheter.
The medical team requests that the psychiatric consultant assess
the patient’s ability to consent to medical procedures. On
examination, the patient is alert and oriented to person, place,
date, and time. The consultant explains in detail the reason the
catheter is indicated and the medical consequences of failing to
receive appropriate treatment. The patient states, “I don’t want a
catheter.” Which element of informed consent has this patient
partially satisfied?
a. Consent
b. Information
c. Concrete logic
d. Duty
e. Capacity
69. An 11-year-old boy presents in your outpatient clinic with his

father for a routine visit. The father says the child is developing
well. He began playing soccer 2 years ago. The father said that
the boy is sometimes a “sore loser,” and other times he is pleased
with the scores that he achieves. He sometimes thinks he is
“useless” if he doesn’t score at a game. The father said that he
praises the boy whether he scores or not and tries to teach him
new techniques for improving his game when they play together
on the weekends. The son tells you that he feels like he is a good
player and only sometimes thinks that he is the worst player in the
team. According to Erikson’s life cycle stages, the boy is dealing
with what developmental conflict?
a. Intimacy versus isolation
b. Identity versus role confusion
c. Initiative versus guilt
d. Industry versus inferiority
e. Ego integrity versus despair
70. A 24-year-old woman presents in the emergency department

complaining that her nose is crooked. You examine her and find
no evidence that it is abnormal. She pulls out a mirror and looks
at herself. “See,” she says pointing to her nose, “don’t you see
how ugly it is?” She tells you that she cannot continue walking
around in public with this nose. She feels that everyone notices it
and has gone to a number of plastic surgeons to try to get it
corrected. None has been willing to operate on her nose to fix it.
You ask a colleague to examine the patient, and she draws the
same conclusion as you. The patient has:
a. Body dysmorphic disorder
b. Exhibitionism
d. Social phobia
71. A 50-year-old man is brought to your office by his family. He

states that he is doing fine and that he has no memory trouble.
The family, however, states that the patient has become
apathetic, inconsiderate, and neglects his personal care. He has
documented mild memory difficulty. He has no history of coronary
artery disease or hypertension. A workup to date has included
thiamine, vitamin B12, folate, and niacin levels, all of which were
normal. An HIV test was negative. A head CT scan with and
without contrast demonstrated frontal and temporal atrophy. What
is your diagnosis?
a. Major neurocognitive disorder due to Alzheimer’s disease
b. Major frontotemporal neurocognitive disorder
c. Major neurocognitive disorder due to Huntington’s chorea
d. Major vascular neurocognitive disorder
e. Major neurocognitive disorder due to prion disease
72. A 46-year-old woman presents to you for an initial psychiatric

evaluation. She has had long-standing problems with mood and
significant difficulties with interpersonal relationships. She tells
you that she was in psychotherapy for 5 years with a psychiatrist
from another city. She met with him several times a week and
describes talking with him about her early childhood, her
relationships with her parents, and subsequent relationships with
important people in her life. In the end, she felt that she
understood herself a lot better and could have better
relationships, but her mood has remained a problem. The patient
was likely undergoing what kind of treatment?
a. Cognitive-behavioral therapy
b. Psychoanalytic psychotherapy
c. Interpersonal therapy
d. Behavior therapy
e. Dialectical behavioral therapy
73. A 57-year-old man from out of town sees you in the walk-in clinic
to obtain replacement prescriptions because his original
prescriptions have been lost. He explains to you that he is in
recovery from alcohol use disorder with depression and anxiety.
In addition to vilazodone, he is prescribed a medication that his
doctor at home said would decrease his cravings for alcohol. He
can’t recall the name of the medication, but he did drink a large
amount of alcohol one time since he has been on it and did not
feel ill. He thinks the medicine may have worked because he lost
interest in continuing drinking the next day and has not relapsed
since. The medication is most likely to be:
a. Disulfiram
b. Zolpidem
c. Buspirone
d. Naltrexone
e. Metoclopramide
74. A 45-year-old man with alcohol-induced hepatic cirrhosis is

admitted for alcohol detoxification. The attending physician on call
instructs you to treat the patient with routine treatment including
thiamine, folate, and benzodiazepines. She tells you that,
because the patient likely has impaired hepatic metabolism, you
should choose a benzodiazepine that is metabolized by
conjugation and that doesn’t have long-acting metabolites. A
reasonable choice is:
a. Oxazepam
b. Diazepam
c. Chlordiazepoxide
d. Buspirone
e. Clonazepam
75. A 73-year-old man is admitted to the hospital for lobar pneumonia

and develops delirium. In thinking about delirium, you remember
that dementia is a risk factor for the future development of
delirium. In reviewing this patient’s history, you learn that he has a
40-pack-year history of cigarette smoking, hypercholesterolemia,
hypertension, type 2 diabetes mellitus, and coronary artery
disease. This patient has known risk factors primarily for what
type of major neurocognitive impairment/dementia?
a. Major neurocognitive disorder due to Huntington’s disease
b. Major vascular neurocognitive disorder
c. Major neurocognitive disorder due to prion disease
(Creutzfeldt–Jacob–related)
d. Major neurocognitive disorder due to Parkinson’s disease
e. Major neurocognitive disorder due to HIV infection
76. A 56-year-old man with a history of mild hypertension and obesity
presents to his primary care physician for treatment of daytime
sleepiness and fatigue. The patient reports that he has been
becoming progressively more fatigued over the past 2 to 3 years
and has gained around 25 pounds because he has no energy to
move around. He has been increasing his caffeine intake to the
point that he feels jittery and nervous, but he is still tired, dozes
off quite frequently during the day, and has fairly frequent
headaches. After obtaining a detailed medical and psychiatric
history, you ask the patient about his time in bed at night. He
states that he sleeps alone after his last bed partner complained
that he snored very loudly and sounded like he was choking all
night. After completing the interview, you make the following
provisional diagnosis for the patient’s complaints:
a. Hypothyroidism
b. Hyperthyroidism
c. Hypochondriasis
d. Major depression
e. Obstructive apnea hypopnea
f. Narcolepsy
77. As an emergency department triage officer, you have been asked

to develop a protocol for admissions. Whereas it is understood
that any patient might necessitate admission, some conditions are
generally self-limited. A patient in withdrawal from which of the
following medications would most likely necessitate admission?
a. Crack cocaine
b. Crystal methamphetamine
c. Marijuana
d. Barbiturates
e. Nicotine
78. A 35-year-old anesthesiologist is referred to you, an addiction

psychiatrist, for treatment of opioid dependence. The patient
reports that he’s been injecting himself with gradually increasing
doses of fentanyl for the past year. He has tried to quit on his own
several times but finds the withdrawal symptoms to be
unbearable. Colleagues at the hospital where he works began to
notice changes in his behavior and occupational performance.
They staged an intervention that led to his referral here. He is
interested in learning about his treatment options. You tell him
that one option is an FDA-approved outpatient treatment for
opioid dependence. You explain that the medication is a pill that
dissolves sublingually. You caution the patient that if he were to
crush the pill and inject it intravenously, he would find himself in
significant opioid withdrawal. What medication is found in the pill
that would account for this phenomenon?
a. Buprenorphine
b. Methadone
c. Naloxone
d. Flumazenil
e. Acamprosate
79. An elderly man is referred to you by his internist because of

symptoms of depression. As you are taking a thorough history,
you ask the patient if he has ever seen a psychiatrist before. The
patient reports that he indeed had seen a psychiatrist for several
sessions about 30 years ago for a “swallowing problem.” You ask
for more details, and the patient explains that he had felt a knot
near his throat and had gone to see an ear, nose, and throat
surgeon. The surgeon told the patient that he might need a
radical surgery. Fortunately, all the tests came back negative, and
the surgery was not recommended. After that, however, the
patient reports he began having difficulty swallowing, and it was
so bad that he couldn’t swallow solid food. His primary care
physician could not find a medical reason for his difficulty
swallowing and referred the patient to a psychiatrist for this
problem. The most likely diagnosis was:
a. Malingering
b. Conversion disorder
c. Illness anxiety disorder
d. Body dysmorphic disorder
e. Factitious disorder
80. A 35-year-old man is seen in a prison clinic for a routine physical

examination. He tells you that he is in jail for murdering two
people in a botched robbery attempt. When you ask him about his
other criminal history, he relays numerous arrests and some
convictions for theft, assault, drunk driving, and rape. Penal
records indicate a persistent pattern of lying and theft while
incarcerated and that he exhibits no remorse when caught by
authorities. He has never been psychiatrically hospitalized and
denies any episodes of elevated, expansive, or fluctuating mood.
He exhibits no grandiosity, pressured speech, or psychotic
symptoms. Family history is significant for alcohol dependence in
his father and mother and for no history of bipolar disorder. He
calmly reports that his father and subsequent foster parents often
beat him with straps or boards when he was a child. He was
knocked unconscious on several occasions but has no history of
seizures and denies nightmares or flashbacks from the abuse. He
has had suicidal ideation but has not made suicide attempts or
been self-destructive. The most likely diagnosis is:
a. Conduct disorder
b. Posttraumatic stress disorder
d. Bipolar disorder
e. Antisocial personality disorder
81. A 15-year-old boy is brought to his pediatrician’s office because

his parents are embarrassed by his behavior. They report that he
has been intermittently barking and yelping repetitively during
conversations. This behavior persists in public and at school. In
addition, he has periods of bizarre body posturing with jerky upper
extremity movements and snorts like a horse. His parents believe
he is punishing them for setting limits on television and social time
with his friends. The young man denies any retaliation against his
parents. He states that he develops a powerful urge to bark and
yelp and that other times he finds himself moving uncontrollably.
He is upset about his behaviors and feels like a “freak.” The most
likely reason for the young man’s behavior is:
a. Adolescent rebellion
b. Schizophrenia
c. Substance abuse
d. Tourette’s disorder
e. Conduct disorder
82. For a patient with Tourette’s disorder, treatment for mild or

moderate tics involves psychoeducation and psychotherapy.
Education describing etiology and prognosis (improving with age)
to parents, patients, teachers, and caregivers can help out all at
ease. Psychotherapies such as Habit Reversal Therapy help
patients learn techniques to minimize tics. For more severe tics,
medications are used. Which of the following medications are
used to treat tics in Tourette’s disorder?
a. Vilazodone
b. Desvenlafaxine
c. Haloperidol
d. Lamotrigine
e. Atomoxetine
83. A 69-year-old woman is brought in by her family because of their

concerns that she is cluttering their house too much and spending
too much money buying stuff. They report that in addition to
continually buying new items, their mother won’t permit them to
throw anything away. She saves every disposable cup and
container. She stores all newspapers and magazines in case she
needs them in the future. Her children report that the stacks of
newspapers are taking up lots of floor space in the house and
sometimes are so tall that they fall over. They report that there is
so much junk in the home that it is hard to walk, with narrow trails
left between objects in some rooms. The patient reports that her
family simply doesn’t understand her and that she can’t throw
away perfectly good items that have a purpose. She states that
whenever she tries to throw something away or give it away she
becomes exceptionally distressed and anxious. She reports no
other symptoms suggestive of depression or anxiety. What is the
most likely diagnosis in this patient?
a. Excoriation disorder
b. Trichotillomania
c. Obsessive-compulsive disorder
d. Hoarding disorder
e. Kleptomania
84. A 47-year-old man is seen in consultation by his primary care

physician. The patient reports that he has begun having difficulty
during sexual activity and that it is disturbing him a great deal.
The patient reports that he develops and maintains penile
erections with no problem but that he is unable to ejaculate during
sex. He finds his sex partner highly attractive and otherwise
enjoys all the sexual activity. But, his inability to ejaculate and
achieve orgasm is creating anxiety and tension in his relationship.
For the past 8 months, the inability to ejaculate has occurred
during all sexual activity with his partner. He does not reports
symptoms or history of other psychiatric problems. He saw a
urologist who completed an appropriate workup and found no
mechanical or biologic cause for his condition. The most likely
diagnosis in this patient is:
a. Male hypoactive sexual desire disorder
b. Delayed ejaculation
c. Substance/medication-induced sexual dysfunction
d. Erectile disorder
e. Priapism
85. A 65-year-old woman is referred for psychiatric evaluation

because she is acting erratically. Her family reports that she is at
times sleepy and very difficult to awaken while at other times she
is agitated and irritable, often threatening them. The patient
reports that there is nothing wrong with her except that her family
is ungrateful. She states that she has been under a lot of stress
lately because she has had multiple losses and recounts that she
was the primary caregiver for two elderly family members who
died over the past year. Since that time, she has tried to volunteer
in an elder care home and a hospice so that she can “contribute
back to others.” On evaluation, the patient reports use of
oxycodone 10 mg four times per day that is prescribed for chronic
back pain. She denies using more than prescribed or running out
early. You check the state-controlled substance monitoring
database and also that of an adjoining state that is only about 40
miles from the patient’s home. The database suggests that the
patient has filled multiple opioid prescriptions from multiple
doctors in two states. What is the most likely diagnosis for this
patient?
b. Intermittent explosive disorder
c. Major depressive disorder
d. Opioid use disorder
e. Substance-induced mood disorder
86. An 18-year-old college student is brought to the emergency room

by the campus police because he has created a disturbance on
campus. On examination, he has auditory hallucinations,
agitation, and rapid, incoherent speech. The length of time that he
has had the symptoms is unknown. Substance abuse history is
unknown. The most likely diagnosis is:
a. Schizophreniform disorder
b. Winter depression
d. Atypical depression
e. Obsessive-compulsive disorder
87. A 4-year-old boy watches his father use a fork. The child then
raises a fork and uses it in a similar fashion to feed himself. This
is an example of:
a. Projection
b. Regression
c. Modeling
d. Classical conditioning
e. Operant conditioning
88. A 28-year-old woman arrives at your office on time for her weekly
psychotherapy session. She appears more distressed than usual,
and you ask her if everything is all right. At first, she appears
embarrassed, but then she confides in you that a disturbing
incident occurred on the subway on the way to your office. She
reports that since the subway car was crowded, she had to stand.
A few seconds before the doors opened, she suddenly felt a man
rubbing his genitals against her back. Before she could say
anything, the doors opened, and the man was gone. She wasn’t
able to get a look at him. This man likely suffered from a
paraphilia called:
a. Exhibitionism
b. Fetishism
c. Frotteurism
d. Pedophilia
e. Voyeurism
89. A 56-year-old man is seen in a psychotherapy intake visit. He

reports that he has been having a great deal of distress, shame,
and embarrassment because he has been secretly buying
women’s clothing and underwear. He is married to a woman and
engages in cross-dressing when he is on business trips and when
she is away. He reports that he doesn’t understand why he likes
to wear women’s clothing, but that it is highly erotic for him, with
the fantasies and action of cross-dressing producing strong
sexual arousal. The most likely diagnosis is:
a. Voyeuristic disorder
b. Exhibitionistic disorder
c. Transvestic disorder
d. Sexual masochism disorder
e. Sexual sadism disorder
90. A 23-year-old female graduate student is brought to the

emergency room by her roommates. They report that they are
very worried about the patient because she will not eat, has been
forcing herself to vomit after eating, and has lost considerable
amounts of weight. The patient reports that she feels fine and that
she has been monitoring her food intake because she does not
want to get fat and eats enough but just doesn’t have an appetite.
On examination, the patient’s height is 5’ 6” inches and she
weighs 94 pounds. You compute her body mass index (BMI) and
find it to be 15.2 kg/m2. What is the most likely diagnosis for this
patient?
a. Major depression
b. Rumination disorder
c. Avoidant/restrictive food intake disorder
d. Bulimia nervosa
e. Anorexia nervosa
91. On the basis of the patient’s low BMI in the preceding question,
you order a medical workup including EKG, comprehensive
metabolic panel (primarily to assess for electrolytes), CBC, and
thyroid hormone studies. While awaiting laboratory results, you
decide that the patient needs to be admitted to an inpatient eating
disorders program after medically evaluated and appropriate
treatment is provided if needed. What types of treatments are
used to treat anorexia nervosa?
a. Medications of the SSRI class
b. Psychotherapy, irrespective of nutritional status
c. Psychotherapy once medical condition has stabilized
d. Bupropion
e. Atomoxetine
92. A 19-year-old college freshman is seen at the student

psychological counseling center with the complaint that she can’t
control her appetite. The patient reports intermittent episodes of
binge eating where she ingests large quantities of calories at a
single setting. She reports that she tries to control her appetite but
then has the uncontrollable urge to eat and loses control of the
situation. She has noted ongoing weight gain that is quite
distressing. Pharmacologic management of this condition
includes:
a. Olanzapine
b. Lurasidone
c. Lisdexamphetamine
d. Valproic acid
e. Phenytoin
93. A 39-year-old man with severe alcohol use disorder is seen after
discharge from an alcohol rehabilitation and treatment facility. He
underwent detoxification from alcohol with benzodiazepines,
followed by 30 days of residential treatment with group and
individual psychotherapy, and was started on treatment with
naltrexone to help reduce cravings and alcohol use. What brain
regions are most strongly implicated in alcohol use disorder and
other addictive disorders?
a. The cerebellum
b. Suprachiasmatic nucleus
c. Ventral striatum/nucleus accumbens
d. The pulvinar nucleus
e. The mamillary bodies
94. An 18-year-old college freshman is evaluated at the university’s

student counseling center. He reports that since starting college
that he has had a great deal of anxiety related to interacting with
his peers and eating in the cafeteria. He has been avoiding public
places and eating at fast food restaurants and from vending
machines. He doesn’t report depressed mood or symptoms
suggestive of panic disorder but feels as if he is being scrutinized
and judged by others in social circumstances. The most likely
diagnosis for this patient is:
a. Agoraphobia
b. Generalized anxiety disorder
c. Panic disorder
d. Social anxiety disorder
e. Dependent personality disorder
95. A 9-year-old child has biologic characteristics typical of a female

and has been raised as a female until this point. However, the
child repeatedly asserts a desire to be male. The child has strong
desire to be male, strong preference for male playmates, toys,
and clothing typical of males, and a desire to manifest secondary
sex characteristics of a male. The child becomes very upset when
encouraged to dress and behave in a gender-typical manner and
when adults assert that the child is a girl. What is the most likely
diagnosis for the child?
a. Transvestic fetishism
b. No diagnosis
c. Adjustment disorder
d. Gender dysphoria
e. Illness anxiety disorder
96. A 33-year-old man is seen in your primary care practice with

concerns that he might have cancer. The patient reports that he
thought he had a small lump in his testicles and that he is worried
that he has testicular cancer. The patient reports that he has
presented with similar complaints to other physicians and has had
multiple medical workups including diagnostic imaging and blood
work. The other physicians told him that there was nothing wrong
and that he does not have cancer or any other problems. The
patient was not reassured and just feels that something is
seriously wrong although he is willing to accept that he could be
okay and just overly worried. He has read a great deal about the
topic on the Internet and worries that a diagnosis can be missed
sometimes. He has no specific symptoms suggestive of somatic
illness. The most likely diagnosis is:
a. Avoidant personality disorder
b. Somatic symptom disorder
c. Illness anxiety disorder
e. Generalized anxiety disorder
97. A 57-year-old man with a history of chronic alcoholism is placed
in a nursing home for alcohol-related major neurocognitive
disorder. This condition is associated with damage to the
following brain regions:
a. The brain stem and frontal lobes
b. The hippocampus, fornix, and mammillary bodies
c. The thalamus and cingulate gyrus
d. The caudate and putamen
e. The cerebellum
98. A 68-year-old woman presents to the emergency room with

depression and suicidal thinking. The patient reports that she has
been struggling with depression for a long time but that it has
been getting worse with increased suicidal ideation. The patient
also reports drinking on average one pint of vodka per day, along
with occasional beer and wine for the past 2 years. She states
that alcohol helps her sleep and cope. She does not report
depressive symptoms before alcohol use. The best next step in
this patient’s management is:
a. Treat the patient for bipolar disorder
b. Refer the patient to Alcoholics Anonymous
c. Admit to the inpatient unit for alcohol detoxification and start an
antidepressant
d. Admit to the inpatient unit for alcohol detoxification without
starting an antidepressant
e. Refer to outpatient treatment
99. A 12-year-old girl presents with her foster mother for a routine
pediatric visit. The girl seems quiet, and she does not make eye
contact with you as you enter the room. Her foster mother says
that the girl has been having difficulties socially in school. She
has trouble making friends and often has conflicts with
classmates. She has trouble seeing the “big picture” of problems
that face her, and she often gets lost in the details of projects that
she is assigned. She is awkward in her interactions. Her foster
mother says that she can be quite verbally articulate and writes
extremely well. You query her for depressive or psychotic
symptoms and she denies either. Once you ask her about one of
her projects, and she tells you about the intricacies of building a
radio from scratch. She engages with you briefly but still appears
uncomfortable. She denies any significant anxiety. The most likely
diagnosis is:
a. Autism spectrum disorder
b. Intellectual disability
c. Avoidant personality disorder
d. Anxiety disorder not otherwise specified
100. A 41-year-old man with a 21-year history of bipolar disorder

comes to the emergency department with ataxia, coarse tremor
of his upper extremities, confusion, and diarrhea. He reports
that he has been sweating a great deal because it is “so hot
outside” and that he gets “no relief” at home because his
halfway house is not air-conditioned. His medications are
fluoxetine 40 mg per day, lithium carbonate 300 mg each
morning and 600 mg each evening, oxcarbazepine 300 mg
each morning and 900 mg each evening, olanzapine 7.5 mg
each evening, and lorazepam 1 mg per day. He denies having
used any illicit drugs. On examination, his heart rate is 100
and regular, blood pressure is 98/60 mm Hg, respiratory rate is
14 breaths per minute, and temperature is 98.7°F. The most
a. Lithium toxicity
b. Lorazepam toxicity
c. Fluoxetine toxicity
d. Oxcarbazepine toxicity
e. Serotonin syndrome
101. A 59-year-old woman is seen in the emergency room with the

complaint of ongoing depression with suicidal ideation. The
patient has tried and failed multiple antidepressant medications
and combinations of antidepressants and other augmenting
strategies. She has been recommended for ECT or TMS but is
afraid of electrical treatments. She heard that there is an
emerging treatment for depression and suicidal ideation that
works quickly in some people. What is the most likely treatment
that the patient is referring to?
a. Aromatherapy
b. Phototherapy
c. Vagal nerve stimulation
d. Melatonin
e. Ketamine
102. A 32-year-old single woman presents to your family practice

office for an initial visit. Although it is 10:00 am, she is dressed in
black leather pants, a tight low-cut pink top, and is wearing full
makeup. She sits down with ease, leans forward, and proceeds to
tell you all about her vibrant social life in a highly dramatic and
overfamiliar manner. You are aware that you feel quite
uncomfortable in her presence because of her seductiveness.
Although she reports that she has many friends, you notice that
she appears to include brief acquaintances such as the mailman
among her confidants. You suspect the presence of which of the
following personality disorders?
a. Antisocial
b. Avoidant
c. Dependent
d. Histrionic
e. Schizoid
1. e, lithium (Chapter 17)
This patient is showing classic signs and symptoms of lithium toxicity.
Nausea, vomiting, diarrhea, and tremor or ataxia are common.
Pertinent risk factors for development of toxicity include congestive
heart failure, renal insufficiency, and use of thiazide diuretics.
Haloperidol, valproic acid, or ziprasidone might have been reasonable
choices for the treatment of the patient’s bipolar disorder but would not
have caused symptoms consistent with the current presentation.
Paroxetine, used primarily as an antidepressant, might worsen
hypomania or mania but would not cause symptoms consistent with
the patient’s presentation.
2. c, benztropine (Chapter 19)

The symptoms described in the question are strongly suggestive of
anticholinergic toxicity due to the antimuscarinic action in the
peripheral and central nervous system. Benztropine is an
anticholinergic medication commonly used in psychiatry to treat or
provide prophylaxis for some types of neuroleptic-induced movement
disorders. None of the other answer choices listed has substantial
anticholinergic activity. However, patient’s often take a mixture of
medications in overdose so one should be vigilant for signs of other
drug toxicity, even when one predominates. Fluoxetine is a selective
serotonin reuptake inhibitor that may produce serotonin syndrome,
especially in overdose or when taken with other medications
influencing serotonin function. Haloperidol is a first-generation
antipsychotic that produces neuroleptic-induced parkinsonism at both
therapeutic dosages and markedly so in overdose. Haloperidol is also
associated with neuroleptic malignant syndrome (NMS). Diazepam is
a benzodiazepine that would produce marked sedation or loss of
consciousness in sizeable overdose. Hydrocodone is an opioid that
would produce respiratory depression, decreased level of arousal, and
pupillary constriction in overdose. Opiates can cause death when
taken in excess due to marked capacity for respiratory depression.
3. b, neutropenia (Chapter 15)

This patient has severe and persistent psychosis that has been poorly
responsive to treatment with antipsychotic medications. After his most
recent severe psychotic break, he has been started on a medication
that requires regular blood draws. The medication described is
clozapine, an atypical antipsychotic that is considered the “gold
standard” treatment for refractory psychosis. This medication requires
regular monitoring of complete blood count and differential due to the
rare but potentially fatal side effect of severe neutropenia. Because of
this risk, the absolute neutrophil count (ANC) must be ≥1,500/mm3 for
most people. This patient has developed signs and symptoms
consistent with a possible respiratory infection in the context of
treatment with clozapine. Neutropenia must be urgently excluded by
drawing a complete blood count and differential.
4. a, oxycodone (Chapter 10)

The patient has developed anxiety, agitation, gooseflesh, yawning,
rhinorrhea, tachycardia, and dilated pupils 48 hours after
hospitalization. These symptoms are consistent with opioid
withdrawal. This patient has likely been taking an opioid analgesic
such as oxycodone on an outpatient basis for chronic back pain and
has abruptly discontinued the medication as an inpatient, resulting in
acute withdrawal. Alcohol withdrawal presents with hypertension,
tachycardia, diaphoresis, nausea, and a prominent tremor 24 to 48
hours after abrupt discontinuation. Alprazolam withdrawal presents
similarly to alcohol withdrawal and is potentially life threatening with
hypertension and risk of seizures. Amphetamine and cocaine
withdrawal present with dysphoria, headache, increased appetite, and
excessive sleepiness.
5. b, attention-deficit hyperactivity disorder (Chapter 8)
The child meets the criteria for attention-deficit hyperactivity disorder
(ADHD). This disorder is characterized by a persistent attention
disturbance in at least two settings (such as school and home)
accompanied by hyperactivity. The child does not display evidence of
a formal thought disorder or ongoing psychosis, and so would not
meet the criteria for schizophrenia. Tourette’s disorder is
characterized by involuntary vocal and motor tics. Separation anxiety
disorder is characterized by anxiety as evidenced by behavior
disturbance (such as crying) when separated from a primary
caregiver. Autism spectrum disorder is characterized by impaired
social interactions and impaired communication along with restricted
interests or behaviors.
6. e, bipolar disorder, type I, most recent episode depressed

(Chapter 2)
The patient presents with symptoms of a depressive episode. The
history of apparent manic episodes (her reported symptoms—lots of
energy, decreased need for sleep, overspending on credit cards,
sudden travel, and grandiose delusions of being the savior of the
world are too severe to be considered hypomania) makes the
diagnosis bipolar type I with the current episode of depression being
the most recent episode. Although the patient may have psychotic
features when she is manic (grandiose delusions), depression with a
history of psychosis while manic is more consistent with bipolar
disorder than major depression with psychotic features.
7. b, olanzapine (Chapter 15)

The patient’s most likely diagnosis is schizoaffective disorder given
her bouts of depression and psychosis and the presence of psychosis
in the relative absence of depression. A childhood diagnosis of
attention-deficit disorder sometimes reflects cognitive difficulties that
present in children who will later go on to develop a psychotic
disorder. Her current presentation is one of command hallucinations to
kill herself. Dextroamphetamine would not reduce hallucinations and
would likely exacerbate them via its effect on increasing synaptic
dopamine levels. Vortioxetine and clomipramine are primarily
antidepressants that may improve her mood but would not treat the
hallucinations. Similarly, lithium may improve or affect mood but will
not help to alleviate hallucinations. Olanzapine, the only antipsychotic
in the list, is the most appropriate therapy.
8. d, lithium (Chapter 17)

In the absence of an identifiable organic cause, this patient meets
clinical criteria for mania by exhibiting elevated mood plus at least
three other symptoms, including pressured speech, grandiosity,
excess involvement in pleasurable activities (spending), and
decreased need for sleep for at least 1 week. Lithium is a mood
stabilizer that is of benefit in treating mania and in maintenance
treatment in patients with bipolar disorder. In addition, lithium reduces
suicidal behavior in mood disorders. Buspirone is used in the
treatment of generalized anxiety disorder, has a delayed onset of
action, and is of no benefit in the treatment of mania. Fluoxetine is a
serotonin reuptake inhibitor class of antidepressant and would also
potentially worsen mania. Liothyronine (T3) is used as an adjunct to
antidepressant medication to improve treatment outcome and would
potentially worsen mania. Phenelzine is a monoamine oxidase
inhibitor class of antidepressant, which would potentially worsen
mania.
9. c, cocaine (Chapter 10)

This patient is a young man with no medical risk factors for cardiac
disease. Despite this, he presents acutely to the emergency room with
a myocardial infarct. The following day, he appears acutely depressed
and fatigued with a headache and increased appetite. This picture is
most consistent with cocaine abuse or dependence due to the
association between cocaine use and coronary vasoconstriction and
symptoms of stimulant withdrawal the day after admission. Withdrawal
from central nervous system depressants including alprazolam,
alcohol, and clonazepam presents with coarse tremor, nausea and
vomiting, diaphoresis, tachycardia, and hypertension. Withdrawal from
cocaine or stimulants presents with fatigue, depression, headache,
muscle cramps, sweating, and hunger. Withdrawal from opiates such
as morphine presents with anxiety, agitation, gooseflesh, yawning,
rhinorrhea, tachycardia, and dilated pupils.
10. b, arrhythmia (Chapter 16)

Tricyclic antidepressants at nontoxic doses are associated with
multiple side effects including orthostatic hypotension; anticholinergic
effects including dry mouth, blurred vision, and urinary retention; and
sexual dysfunction. However, the most serious side effect is a
quinidine-like effect on the heart that can cause a variety of cardiac
disturbances including supraventricular tachyarrhythmias; ventricular
tachycardia; prolongation of the PR, QRS, and QT intervals; bundle
branch blocks; and ST or T wave changes. These effects can be fatal.
Consequently, this patient requires a medical admission for
continuous cardiac monitoring.
11. d, provide the patient with orienting cues such as names,

clocks, and calendars (Chapter 9)
Delirium is a very serious medical condition that is associated with
brain volume loss and persistent cognitive impairments so all attempts
should be made to resolve the delirium as quickly as possible. The
treatment of delirium involves keeping the patient safe from harm
while addressing the underlying cause of the illness. Although alcohol
or benzodiazepine withdrawal delirium is often treated with
benzodiazepines, benzodiazepines may worsen or precipitate delirium
arising from other causes. Nonpharmacologic approaches should be
employed for management of every delirious patient. These
approaches include strategies for reorientation and behavioral
intervention, such as ensuring the presence of family members,
orienting influences, use of sitters, and transferring a disruptive patient
to a private room or closer to the nurse’s station for increased
supervision. Personal contact and communication are critical,
incorporating reorientation strategies, simple instructions, and frequent
eye contact. Clocks, calendars, and the day’s schedule should be
provided to assist with orientation. Room and staff changes should be
kept to a minimum. A quiet environment with low-level lighting is
optimal for the delirious patient. Pharmacotherapy is widely used in
the clinical treatment of delirium. Although not FDA approved in the
United States, both typical and atypical antipsychotic medications are
often used, especially in the context of agitation in delirium. The
impact of antipsychotics on the course of delirium has not been
demonstrated so they should be used sparingly and when needed for
behavioral control to enhance patient safety.
12. e, dissociative amnesia (Chapter 5)

The essential feature of dissociative amnesia is an inability to recall
important personal information, usually of a traumatic or stressful
nature, that is too extensive to be explained by normal forgetfulness.
This disorder involves a reversible memory impairment in which
memories of personal experience cannot be retrieved in a verbal form.
The duration of the amnesia can last from minutes to many years.
This patient’s symptoms are characteristic of “localized amnesia” in
that she forgot events from a specific time period. Given the nature of
the trauma she experienced, this patient would be at risk for PTSD
and dissociative amnesia can be a symptom of PTSD. However, the
history does not provide broader symptoms, such as hypervigilance,
flashbacks (recurrent involuntary memories), nightmares, avoidance,
and suggestive of PTSD. The essential feature of dissociative identity
disorder is the presence of two or more separate personalities that
recurrently take control of a person’s behavior. Depersonalization
disorder is a pervasive sense of being detached from or being outside
of one’s body. With a seizure, the memory impairment is sudden in
onset, motor abnormalities may be present, and repeated EEGs
reveal typical abnormalities.
13. e, Major neurocognitive disorder due to Alzheimer’s disease

(Chapter 9)
The patient is found isolated and living in squalid conditions. She is
apparently paranoid and socially withdrawn but also exhibits profound
cognitive deficits and evidence of frontal lobe dysfunction on cognitive
and MRI examinations. While she may be depressed or have social
phobia, this does not explain the full picture. Her paranoia is
consistent with delusional disorder or schizophrenia, but this does not
explain the cognitive impairment. Major neurocognitive
disorder/dementia (with the most common type being Alzheimer’s
disease) could explain the social isolation, cognitive difficulties, and
frontal lobe (executive) impairments and is often seen with psychotic
symptoms.
14. b, borderline personality disorder (Chapter 11)

This patient meets criteria for borderline personality disorder. The
hallmarks of this disorder are pervasive instability in interpersonal
relationships, self-image, and affect, and significant impulsivity
beginning by early adulthood. This patient experiences unstable
relationships in which she varies between idealizing and devaluing her
boyfriends, disturbed identity in which she feels empty and a lack of
purpose, difficulty controlling her emotions with severe loss of temper,
impulsive behaviors with the potential to be self-damaging including
drug abuse and self-mutilation, and recurrent suicidal behavior.
Patients with antisocial personality disorder disregard usual societal
roles and lack empathy. Patients with avoidant personality disorder
feel inadequate and thus avoid relationships despite desiring them.
Patients with dependent personality disorder rely on others for support
and guidance with decision making. Patients with schizoid personality
disorder are emotionally detached.
15. a, dialectical behavioral therapy (DBT) (Chapter 21)

DBT has strong empirical support and is the first-line
psychotherapeutic modality in the treatment of borderline personality
disorder. DBT incorporates aspects of cognitive-behavioral therapy
(CBT), Zen philosophy, sociology, and psychology and focuses on the
patient and therapist accepting the patient in the present as a
foundation for developing important behavioral and emotional skills.
Crisis intervention is limited psychotherapy delivered at the time of a
traumatic incident with the aim of minimizing long-term psychiatric
pathology. Family therapy explores hierarchies within the family
system and is of particular use in child psychiatry. Interpersonal
psychotherapy focuses on the patient’s relationships with others.
Psychodynamic psychotherapy is largely derived from the theories of
Sigmund Freud and strives to improve patients’ understanding of
themselves through addressing unconscious conflicts.
16. c, delirium (Chapter 9)

This patient has developed a severe complication following a motor
vehicle accident. The patient has developed dysfunction in multiple
executive domains including memory, orientation, arousal, and
perception. The abrupt time course argues against a diagnosis of
dementia. Depression may be associated with sleep–wake cycle
disturbances, psychosis, agitation, and memory loss, but there is no
evidence for mood disturbance or change in neurovegetative
symptoms in the patient for a period of 2 weeks. Furthermore, the
degree of disorientation and attention impairment is not characteristic
of depression. Dissociative identity disorder may present with
apparent confusion or odd behavior and loss of awareness of self-
identity, but the presence of agitation, dysfunction in multiple cognitive
domains, and psychosis are not suggestive of this diagnosis.
Schizophrenia is unlikely because the patient has no history of
negative symptoms and has only 48 hours of “seeing bugs,” a
symptom potentially consistent with psychosis.
17. b, alcohol withdrawal (Chapter 10)

Alcohol withdrawal is a life-threatening complication of abrupt
cessation of alcohol intake in alcohol-dependent individuals. Although
there is no provided history of alcohol dependence for this patient,
alcohol withdrawal is often the first indicator of a history of alcohol
dependence following trauma such as motor vehicle accident or other
accident. Opiate intoxication would present with respiratory
depression, mental obtundation, and reduced blood pressure. Cocaine
withdrawal presents with symptoms of fatigue, depression, headache,
hunger, and apathy but not with agitation or severe confusion. Sleep
apnea may produce mental clouding or headaches and daytime
fatigue. Anemia can contribute to delirium as part of a multifactorial
delirium, but mild anemia in an otherwise healthy individual with good
oxygen saturation is not likely to be of clinical importance. Another
important cause of delirium following trauma with long-bone fractures
is fat emboli syndrome and should always be considered in the
differential diagnosis of postinjury delirium.
18. d, flight of ideas (Chapter 1)

The patient is not able to answer your original question, and she
switches rapidly from one topic to another. However, there is still a
loose connection between sentences. This describes flight of ideas
and is indicative of impairment in thought process. Circumstantiality
describes an indirect thought process that does eventually
spontaneously address the original question and can be normal.
Poverty of thought describes diminished richness and content, as is
frequently seen in residual schizophrenia. Tangentiality describes
logical thought processing that does not answer the original question.
Word salad describes severe breakdown in thought process in which
no meaning is conveyed and speech consists of a string of words that
do not form sentences.
19. e, the patient continues to threaten his mother (Chapter 14)

Today, commitment laws typically require that the involuntarily
detained person have a mental disorder and pose a risk of harm to
self or others. The risk of self-harm can be either from intentional acts
or from an inability to meet safely the ordinary demands of life in the
community—the so-called “grave disability.” If safety can be
reasonably ensured through options less restrictive than involuntary
hospitalization, those options generally must be pursued. Commitment
laws typically empower psychiatrists to effect emergency detention
without judicial review for periods of a few days to a few weeks.
Further detention, however, requires judicial review. Although
diagnostic details are not provided in the available history, the
presence of paranoia and auditory hallucinations supports a diagnosis
of a psychotic mental illness. Therefore, the patient meets criteria for
(1) presence of mental illness and (2) risk of harm to self or others.
20. b, major depression with atypical features (Chapter 3)

In this case, the specification of “with atypical features” is applied to
this recent major depressive episode. The essential features are mood
reactivity, meaning the capacity to be cheered up when presented with
positive events, and the presence of at least two of the following
features: increased appetite or weight gain, hypersomnia, leaden
paralysis, and a long-standing pattern of extreme sensitivity to
perceived interpersonal rejection. These features predominate during
the most recent 2-week period. In order to be diagnosed with bipolar
disorder, one must have met criteria for at least one manic or
hypomanic episode in their lifetime. There was no mention of any
history of mania or hypomania with this patient. The essential feature
of a rapid-cycling bipolar disorder is the occurrence of four or more
mood episodes during the previous 12 months. Seasonal affective
disorder is a recurrent mood disorder with a seasonal pattern but we
are not provided information about seasonal changes in mood.
Chronic fatigue syndrome is characterized by chronic fatigue that lasts
more than 6 months. Physical or mental activity often makes the
symptoms worse, and rest usually doesn’t improve the symptoms.
21. a, integrity (Chapter 21)

According to Erik Erikson’s model, individuals pass through a series of
life cycle stages. Each stage presents core conflicts produced by the
interaction of developmental possibility with the external world. Ego
integrity versus despair involves late-life acceptance of one’s place in
the life cycle versus regret of unfulfilled earlier life desires. Basic trust
versus mistrust occurs before 18 months of age when the infant
develops a sense of trust and hope due to being well cared for.
Generativity occurs between ages 40 and 60 if the individual develops
a positive view of his or her role in life and a sense of commitment to
society at large. Intimacy as opposed to isolation occurs in young
adulthood. Industry versus inferiority is the stage between ages 5 and
13 when the child develops a sense of mastery and competence over
creating.
22. e, electroconvulsive therapy (ECT) (Chapter 16)

This patient is severely depressed despite antidepressant medication,
as evidenced by the development of psychomotor retardation and
psychotic nihilistic delusions. Rapid treatment of her depression is
indicated due to her development of dehydration as evidenced by
rising urea and urine specific gravity. Consequently, ECT is indicated
due to its high efficacy and rapidity of onset in the treatment of
depression. The induction of a generalized seizure is required for this
treatment to be effective. Switching to a monoamine oxidase inhibitor
or tricyclic antidepressant or augmenting with liothyronine are all
psychopharmacologic strategies to boost antidepressant treatment,
but all of these methods require time to produce a clinical effect.
Augmenting with an atypical antipsychotic such as quetiapine
fumarate would target the nihilistic delusions, but this would take time
to produce a clinical effect and the immediate concern is the patient’s
safety and medical condition.
23. b, exposure therapy (Chapter 21)

Exposure therapy involves the use of exposure to the feared stimulus.
This is achieved either through graded exposure to increasingly
anxiety-provoking stimuli (as in this patient), which is known as
systematic desensitization, or direct exposure to the anxiety-provoking
stimulus, which is known as flooding. This approach initially results in
an acute increase in anxiety, which then rapidly declines. Biofeedback
involves measuring signs of physiological arousal, feeding this
information back to the patient and asking the patient to use relaxation
techniques to reduce these signs. Cognitive-behavioral therapy (CBT)
involves identifying and challenging core cognitive distortions and the
use of behavioral techniques to treat depression, social phobia,
obsessive-compulsive disorder, posttraumatic stress disorder, or panic
disorder. Psychodynamic therapy examines unconscious conflicts.
Supportive therapy involves providing empathy and bolstering a
patient’s character strengths to improve their functional status.
24. c, unilateral electrode placement (Chapter 16)

Unilateral electrode placement is less efficacious than bilateral
electrode placement but is associated with fewer cognitive side
effects, including short-term memory impairment and confusion.
Antipsychotics have their own side effects and might add to cognitive
problems. Benzodiazepines raise the seizure threshold and might also
add to cognitive problems. Intravenous caffeine is sometimes
administered before ECT treatment to lower seizure threshold and
therefore aid with seizure induction but not commonly. Older age is
not a contraindication to ECT, and many elderly patients benefit from
this treatment modality, which has a good track record of safety.
However, they are more likely to have significant medical
comorbidities than are younger patients, which can increase their risk
of complications from undergoing general anesthesia or the procedure
itself.
25. b, catatonia (Chapter 1)

This patient has a bipolar mood disorder, which is a risk factor for the
development of catatonia. This is a syndrome of pronounced
movement abnormalities associated with many psychiatric and
medical disorders. Catatonia (in the DSM-5 rubric) requires three or
more of the following criteria to be met: stupor, catalepsy, waxy
flexibility, mutism, negativism, posturing, mannerism, stereotypy,
agitation, grimacing, echolalia, or echopraxia. This patient exhibits
mutism, posturing, echopraxia, and waxy flexibility (maintaining a pose
he is placed in). In addition, he demonstrates gegenhalten (increasing
resistance through a range of motion), and automatic obedience
(obeying your command to allow you to put a pin through his tongue),
which are symptoms found on alternative catatonia rating scales.
Cataplexy is sudden loss of muscle tone in response to strong
emotion and is seen in narcolepsy. Delirium is global cerebral
dysfunction that is associated with disorientation and waxing and
waning of conscious level. Malingering involves consciously
manifesting symptoms with the purpose of secondary gain.
26. d, benzodiazepine (Chapter 18)

About 70% to 80% of catatonia responds well to treatment with
benzodiazepines, and there is often a rapid response following a dose
of medication. The response can be very rapid if administered
intravenously. Catatonia is also an indication for electroconvulsive
therapy (ECT) and responds rapidly to this treatment. Alpha-
adrenergic agonists are commonly used in psychiatry for symptoms of
PTSD. Antidepressants are not specifically indicated in a patient
without depression or another condition responsive to antidepressants
and might worsen mania in this patient. Cholinesterase inhibitors are
used mainly to treat cognitive deficits in major neurocognitive
disorders. Mood stabilizers might prevent another manic episode but
there is little evidence for their effect on catatonia. Emerging literature
in the form of case reports suggest some efficacy from amantadine,
which is thought to work by increasing dopamine levels, and
memantine and NMDA receptor antagonist.
27. e, clozapine (Chapter 15)

Parkinson’s disease (PD) is the most common form of a group of
progressive neurodegenerative disorders characterized by the clinical
features of parkinsonism, including bradykinesia (a paucity and
slowness of movement), rest tremor, muscular rigidity, shuffling gait,
and flexed posture. The symptoms are caused by a loss of dopamine
neurons in the substantia nigra. The loss of neurons in this region
leads to depletion of the neurotransmitter dopamine. The
dopaminergic system that arises from the substantia nigra controls
voluntary movement by the striatum. Antipsychotic medications block
dopamine receptors (mainly the D2 receptor) and therefore can cause
as a side effect called extrapyramidal symptoms, also known as
neuroleptic-induced parkinsonism. In other words, by blocking
postsynaptic dopamine receptors in the nigrostriatal dopamine
pathway, antipsychotics may cause patients to have symptoms of
rigidity and akinesia that look like the classic symptoms of Parkinson’s
disease. All of the antipsychotic medications listed are known as
typical antipsychotics and have significant potential to cause
extrapyramidal symptoms except clozapine. Clozapine is an atypical
antipsychotic and is much less likely to cause extrapyramidal
symptoms due to its receptor-binding profile, which includes blockade
of serotonin 2A receptors in addition to D2 blockade among other
actions.
28. e, Tarasoff (Chapter 14)

The Tarasoff court decisions provide the primary judicial guidance for
breaking patient–doctor confidentiality in the context of warning
potential victims of violence. Tarasoff part I states that clinical
providers have a duty to warn the potential victims of their patients of
the threat to harm them regardless of usual clinical confidentiality
between a patient and provider. Tarasoff part II states that reasonable
measures must be taken to protect a potential victim. You therefore
have a responsibility to break your patient’s confidentiality and make
every effort to warn and protect Donna. Duty is defined as the
responsibilities of a clinician to their patient once a health care
relationship has been established. The Health Insurance Portability
and Accountability Act (HIPAA) addresses maintaining the security
and privacy of health care data. Incapacity is a term meaning that a
patient lacks the ability to make decisions regarding their own health
care. M’Naghten states that a person is not responsible for a criminal
act if he or she has a mental illness or mental retardation and does not
understand the nature of the criminal act or does not realize that the
criminal act is wrong.
29. b, serotonin syndrome (Chapter 20)

Serotonin syndrome results from overstimulation of serotonin
receptors due to high synaptic concentrations of serotonin. Classically,
this syndrome is produced when other serotonin-altering medications
(e.g., clomipramine) are used with monoamine oxidase inhibitors
(MAOIs; e.g., phenelzine). Serotonin syndrome may present with
shivering, hyperreflexia, and clonus as well as nausea and diarrhea.
Both serotonin syndrome and neuroleptic malignant syndrome (NMS)
present with fever, altered mental status, and autonomic instability.
NMS can occur at any time during the use of antipsychotic
medications and is most frequently seen during periods of dehydration
or rapid escalation of dose. Selective serotonin reuptake inhibitors
(SSRIs) are reported to cause a discontinuation syndrome that
typically begins within 5 days after drug discontinuation and may last
up to 3 weeks. The most frequently reported symptoms include
dizziness, lethargy, paresthesias, nausea, vivid dreams, irritability, and
depressed mood. MAOIs inhibit monoamine oxidase in the
gastrointestinal system as well as the brain. Ingestion of
sympathomimetic amines such as tyramine when taking an MAOI can
lead to a hypertensive crisis and potential myocardial infarction or
stroke. Therefore, patients on MAOIs must avoid foods containing
tyramine such as cured meats or fish, beer, red wine, and aged
cheese. Stevens–Johnson’s syndrome is a potential life-threatening
allergic reaction to a drug that is considered to be a severe form of
erythema multiforme characterized by high fever, myalgias, headache,
sore throat, and a blistering rash that involves at least one mucous
membrane.
30. c, prolactin is under tonic inhibitory control by dopamine

(Chapter 15)
Antipsychotic medications can cause prolactinemia by blocking
hypothalamic D2 receptors. Since prolactin is under tonic inhibitory
control by dopamine, this leads to increased release of prolactin by
the pituitary. Symptoms of prolactinemia include galactorrhea,
gynecomastia, amenorrhea, and loss of libido.
31. d, akathisia (Chapter 20)

This patient is experiencing akathisia, a side effect of treatment with
antipsychotic medications. This is described as an internal feeling of
severe restlessness resulting in a strong desire to move one’s body,
frequently manifested as pacing, inability to sit still, anxiety, and
dysphoria. This side effect usually occurs within the first month of
treatment with an antipsychotic medication but can be caused by other
medications, including selective serotonin reuptake inhibitors (SSRIs).
Chorea consists of brief, flowing, semi-purposeful movements that
may develop as a complication of medications including antipsychotics
but is also a hallmark of Huntington disease and may occur as a
complication of rheumatic fever. Dystonia is a muscle spasm and
usually develops within days of starting an antipsychotic medication.
Neuroleptic-induced parkinsonism involves the development of a
mask-like facies, rigidity, and akinesia, sometimes with a 3-to-6-Hz
pill-rolling tremor, in response to antipsychotic medication. It usually
develops within weeks of starting an antipsychotic, and the risk is
increased with use of high-potency neuroleptics rather than the newer
atypical antipsychotic medications. Tardive dyskinesia is a
neuroleptic-induced movement disorder that develops with long-term
treatment and usually consists of constant, stereotyped
choreoathetoid movements.
32. b, conversion disorder (functional neurologic symptom

disorder) (Chapter 12)
Conversion disorder is one of a group of somatic symptom and related
disorders. Somatic symptom and related disorders involve the
expression of physical signs and symptoms in the absence of a known
medical cause. These symptoms are not willfully produced and are
believed to be subconscious in origin. In the case of conversion
disorder, signs and symptoms involve sensory and/or voluntary motor
dysfunction usually in the presence of an acute stressor, as in the
patient described. Histrionic personality disorder is a chronic pattern of
behavior that includes excessive emotionality, superficiality despite a
typical claim of having multiple intimate relationships, dramatic and
provocative behavior, and inappropriate flirtation. Major depressive
disorder involves depressed mood or a loss of interest or pleasure
most of the time for at least 2 weeks along with four other symptoms
including a decrease or increase in sleep, change in appetite,
inappropriate guilt, diminished energy, psychomotor agitation or
retardation, or suicidality. Malingering involves the conscious feigning
of medical signs and symptoms for the purpose of secondary gain.
Somatic symptom disorder involves at least one somatic symptom that
becomes the focus of one’s thoughts and may include concerns about
the seriousness of the condition, severe anxiety about the condition,
or spending a great deal of effort, such as seeing physicians, related
to the condition.
33. a, phenelzine (Chapter 16)

This patient has developed acute symptoms of sympathetic activation
including diaphoresis and pupil dilatation in the context of consuming
Chianti wine, which is particularly rich in the sympathomimetic amine
tyramine. Monoamine oxidase inhibitors (MAOIs) such as phenelzine
are a class of antidepressant medication with the side effect of
inhibiting the gastrointestinal monoamine oxidase system. Hence,
when foods rich in tyramine are consumed, they cannot be detoxified,
resulting in acute sympathetic activation, which can lead to a severe
hypertensive crisis (also known as a tyramine crisis), as in this patient.
Bupropion antagonizes both the norepinephrine and dopamine
transporters. Side effects of bupropion include seizures, particularly in
patients with eating disorders, headache, nausea, gastrointestinal
distress, sweating, anxiety, insomnia, anorexia, and weight loss. Side
effects of selective serotonin reuptake inhibitors (SSRIs) such as
fluoxetine and sertraline include nausea, headache, gastrointestinal
distress, insomnia or sedation, delayed ejaculation or anorgasmia,
and neuromuscular restlessness. Side effects of venlafaxine are
similar to the SSRIs with the addition of hypertension, anxiety, tremor,
sweating, and weight loss likely due to its additional blockade of the
norepinephrine transporter.
34. c, serotonin syndrome (Chapter 20)

Serotonin syndrome is caused by high synaptic concentrations of
serotonin and most frequently results from medications that elevate
serotonin. This patient is taking a monoamine oxidase inhibitor
(MAOI), which increases serotonin at the synapse. She subsequently
takes sumatriptan, which further elevates serotonin levels through its
agonist action at serotonin-1 (5-HT1) receptors. The result is abrupt
onset of serotonin syndrome, including signs and symptoms of
autonomic, motor, and behavioral dysfunction. These include
tachycardia, hypertension, fever, diaphoresis, tremor, myoclonus,
hyperreflexia, agitation, delirium, and coma. Gastrointestinal
symptoms are also usually prominent due to the significant presence
of serotonin in the gut. Hypertensive crisis (tyramine crisis) occurs in
patients taking monoamine oxidase inhibitors (MAOIs) who consume
foods rich in the sympathomimetic amine tyramine. Neuroleptic
malignant syndrome shares features of serotonin syndrome but
occurs in response to antipsychotic medication, involves prominent
rigidity, is usually more insidious, and does not include prominent
gastrointestinal symptoms.
35. b, narcolepsy (Chapter 12)
Patients with narcolepsy experience excessive daytime sleepiness
with sleep attacks, as manifested by your patient during the
psychiatric interview. They also have sudden bilateral loss of skeletal
muscle tone, typically when experiencing strong emotion, which is
known as cataplexy. Rapid eye movement (REM) sleep intrusion is
another feature of the disorder and causes the experience of very
vivid hallucinations at sleep initiation (hypnogogic hallucinations) and
on waking (hypnopompic hallucinations). Obstructive sleep apnea
hypopnea is associated with sleep disruption and excessive daytime
sleepiness due to abnormal breathing during sleep. Nightmare
disorder involves repeated frightening dreams, mainly during REM
sleep. Patients with hypersomnolence disorder have excessive
sleepiness despite sleeping at least 7 hours night, sometimes sleep
over 9 hours, can fall asleep multiple times per day, and may have
trouble waking up. Psychoactive substance use fragments sleep
architecture and is often a cause of insomnia but there is no evidence
for substance misuse in this patient’s presentation.
36. d, industry versus inferiority (Chapter 21)

The child is struggling with Erikson’s life cycle known as industry
versus inferiority. Between the ages of 5 and 13, children struggle with
developing a sense of self on the basis of the things that they create.
Caregivers provide a sense of mastery by teaching and giving
feedback. Initiative versus guilt precedes industry versus inferiority at
ages 3 to 5 and involves the feelings of guilt that ensue when a child
first has enough autonomy to explore the world including things that
the parents may find disturbing. Identity versus role confusion follows
industry versus inferiority and corresponds with adolescence.
Generativity versus stagnation occurs between ages 40 and 60 and is
successful if the individual develops a positive view of his or her role in
life and a sense of commitment to society at large. Finally, ego
integrity versus despair involves late-life acceptance of one’s place in
the life cycle versus regret of unfulfilled earlier life desires.
37. a, major neurocognitive disorder due to Huntington’s disease
(Chapter 9)
Huntington’s disease is an autosomal dominant neurodegenerative
condition that generally presents with a movement disorder followed
by emotional lability or depression and then dementia. Onset is
commonly in the mid-30s. The genetic abnormality is an expanded
trinucleotide (cytosine-adenine-guanine [CAG]) repeat in the HD gene,
located on the short arm of chromosome 4. Autopsy typically reveals
the characteristic marked atrophy of the caudate and putamen.
Parkinson’s disease is usually characterized by several cardinal
features including resting tremor, cogwheel rigidity, bradykinesia, and
gait impairment. Major neurocognitive disorder/dementia in
Parkinson’s disease is a late complication of the disease and is not
inevitable. Major neurocognitive disorder due to frontotemporal
dementia presents as a disorder of behavioral control and loss of
social skills, as well as a disorder of executive cognitive function.
Onset is generally at age 50 to 60. Imaging studies may help make
the diagnosis. On autopsy, “Pick bodies” are a feature of a
frontotemporal lobar degeneration involving abnormalities of the tau
protein. The dementing illness in Alzheimer’s disease is almost always
very gradual and insidious. The earliest clinical manifestations are
short-term memory loss. Typically there are no focal neurologic
findings on examination. Creutzfeldt–Jacob’s disease (major
neurocognitive disorder due to prion disease) presents with the clinical
triad of myoclonus, dementia, and abnormal electroencephalogram.
38. c, posttraumatic stress disorder (Chapter 5)

This patient has endured a traumatic incident of sufficient magnitude
to threaten the physical integrity of herself and her son, and her
response involved fear, horror, and helplessness. Traumas of this
magnitude are a prerequisite for risk of developing posttraumatic
stress disorder (PTSD). PTSD symptoms include reexperiencing the
trauma, including nightmares and intrusive daytime recollections
called flashbacks as experienced by this patient; behaviors to avoid
the trauma, such as this patient’s fear of driving, and detachment with
a sense of shortened future; and symptoms of hyperarousal, such as
the anxiety and exaggerated startle response experienced by this
patient. However, this patient does not meet criteria for PTSD
because the duration of her symptoms has been less than 1 month
and would therefore meet current criteria for acute stress disorder.
Acute stress disorder lasts from 2 days to 4 weeks and begins within 4
weeks of experiencing the trauma. If this patient’s symptoms persist
for over 1 month, she would meet criteria for PTSD. Adjustment
disorder involves the development of emotional or behavioral
symptoms that are beyond the usual range of response to an
identified stressor, resulting in significant distress or impaired
functioning. The symptoms develop within 3 months of exposure to
the stressor and resolve within 6 months or termination of the stressor.
Major depressive disorder requires the presence of depressive
symptoms for at least 2 weeks. One of these symptoms must be
depressed mood or loss of interest or pleasure. Panic disorder
requires recurrent unexpected panic attacks with at least 1 month of
worry about further attacks or the meaning of the attacks (e.g.,
believing they represent heart attacks) or changes in behavior due to
the attacks.
39. b, tricyclic antidepressant (TCA) (Chapter 16)

The relatively serotonin-selective tricyclic clomipramine is considered
the gold standard pharmacologic treatment for obsessive-compulsive
disorder, but its utility is often limited by its side-effect profile.
Therefore, selective serotonin reuptake inhibitors (SSRIs) at high
dose, such as fluvoxamine, are usually tried first due to their more
benign side-effect profile. This patient is experiencing the side-effect
profile associated with tricyclic use, including anticholinergic effects of
dry mouth, blurred vision, urinary retention, cognitive impairment, and
orthostatic hypotension induced by alpha-adrenergic receptor
antagonism. Monoamine oxidase inhibitors (MAOIs) cause dose-
related orthostatic hypotension and may precipitate a hypertensive
crisis because of their prevention of detoxification of the
sympathomimetic amine tyramine (present in a variety of foods).
Norepinephrine–dopamine reuptake inhibitors (bupropion) may cause
headache, nausea, gastrointestinal distress, anxiety, and anorexia,
but the most concerning adverse effect is a seizure. SSRIs are
associated with side effects of nausea, headache, gastrointestinal
distress, insomnia or sedation, and delayed ejaculation or
anorgasmia. Typical antipsychotics such as haloperidol may cause a
variety of acute and chronic movement disorders.
40. c, naltrexone (Chapter 19)

Naltrexone is a mu-opioid receptor antagonist that is clinically effective
at reducing relapse rate, craving, and severity of a relapse in patients
with alcohol dependence. Buprenorphine is a partial opioid agonist
used orally as maintenance treatment for opioid dependence and
intramuscularly to treat symptoms of opioid withdrawal. Due to its
partial agonist properties, it has less abuse potential than a full-opioid
agonist and less likely to cause side effects such as respiratory
depression. Clonidine is an alpha2-adrenergic receptor agonist that
acts on presynaptic autoreceptors, reducing central release of
norepinephrine. It is useful in reducing the adrenergic symptoms
associated with opioid withdrawal. Memantine is an antagonist at
glutamatergic N-methyl-d-aspartate (NMDA) receptors and is used to
treat moderate to severe neurocognitive symptoms in Alzheimer’s
disease. Quetiapine fumarate is an atypical antipsychotic agent that
has significant sedating properties.
41. e, major depressive episode (Chapter 3)

The patient’s symptoms of despondent mood, suicidality, impaired
sleep, decreased energy, lack of interest, and guilt lasting for 3 weeks
are consistent with a diagnosis of major depressive episode. Although
the patient’s symptoms appeared to have developed in response to a
very stressful life event, his symptoms are of sufficient severity to
warrant a diagnosis of major depressive episode rather than
adjustment disorder with depressed features. Chronic depressive
disorder is a type of depressive condition lasting for at least 2 years
with depressed mood most of the time. This condition is characterized
by its long duration and the presence of low-grade depressive
symptoms that do not meet criteria for major depression. Pedophilia is
a paraphilic sexual disorder in which an individual has a primary
sexual interest in prepubescent children. The history, as provided,
does not contain evidence sufficient to rule out pedophilia, but a
relationship between a 21-year-old and a postpubescent 17-year-old
does not suggest the diagnosis. This behavior, although illegal in
many jurisdictions, is not considered a sexual disorder. The patient
does not show symptoms of elevated mood, increased energy,
pressured speech, risk-taking behavior, or other symptoms consistent
with a manic episode. Impaired sleep can be a symptom of manic
episode and usually manifests as decreased sleep but also a sense of
a decreased need for sleep so that the person maintains energy and a
state of alertness. Insomnia disorder is a sleep disorder that is not
characterized by prominent suicidality or neurovegetative symptoms.
This patient displays sleep disturbance in the context of a depressive
episode.
42. b, schizophreniform disorder (Chapter 1)

This young man is at the right age epidemiologically to have a first
episode of a major mental illness. The first concern would be that the
patient has ingested a substance that has caused the episode. The
lack of history from two sources and the negative drug screen make
this less likely. The differential diagnosis once a substance-induced
psychosis is ruled out includes brief psychotic disorder,
schizophreniform disorder, schizophrenia, schizoaffective disorder,
bipolar disorder and potential medical causes such as anti-NMDA
receptor encephalitis. However, although he has trouble sleeping, he
does not appear to have significant symptoms of mania or depression.
He would need to have been exhibiting psychotic symptoms for at
least 6 months to meet criteria for schizophrenia or less than 1 month
to meet criteria for brief psychotic disorder. Patients with schizotypal
personality disorder have odd or eccentric beliefs but do not have
frank delusions and hallucinations like this young man. He may have
anxiety related to his fears but does not exhibit panic attacks.
Schizophreniform disorder is the most likely diagnosis because he
meets criteria for schizophrenia except for the length of the episode.
43. c, diabetes mellitus (Chapter 15)

Atypical antipsychotics, particularly olanzapine and clozapine, can be
associated with increased risk of type II diabetes mellitus, as well as
weight gain and dyslipidemia. It is important to regularly monitor
weight, lipid profile, and fasting blood glucose in all patients taking
atypical antipsychotics to monitor for these severe side effects.
Diabetes insipidus and hypothyroidism are potential side effects from
chronic treatment with lithium. Leukopenia is a rare but life-threatening
adverse effect from treatment with clozapine.
44. d, erotomanic (Chapter 1)

This would be classified as an erotomanic delusion because the
patient’s mother was falsely convinced that this man was in love with
her. This kind of nonbizarre delusion is characteristic of delusional
disorder if there are no other psychotic symptoms. The delusion must
be present for at least 1 month. Antipsychotic medications are
appropriate but often ineffective treatment. The primary treatment is
supportive psychotherapy, taking care neither to support nor to refute
the delusion but to maintain an alliance with the patient. Grandiose
delusions are a false belief that the individual has special abilities or is
in other ways much more important than reality indicates. Jealous
delusions are when a person becomes falsely convinced that his or
her lover is unfaithful. Somatic delusions involve the false belief that
the person has a bodily function disorder. Persecutory delusions are
when a person becomes falsely convinced that others are out to harm
him or her and that he or she is being conspired against in general.
45. b, anticholinergic agent (Chapter 19)

This patient has developed oculogyric crisis, an acute dystonia of the
ocular muscles induced by antipsychotic medications, particularly
high-potency antipsychotics such as haloperidol. His risk factors
include young age, male sex, and the recent introduction of
antipsychotic medication. A particularly feared antipsychotic-induced
dystonia is laryngospasm caused by the resulting airway compromise.
Antipsychotic-induced dystonias may be prevented or treated with
anticholinergic medications such as benztropine or diphenhydramine.
α-2 adrenergic agonists are used to treat the autonomic symptoms of
opioid withdrawal. β-Adrenergic antagonists are sometimes used to
treat autonomic anxiety symptoms in social phobia. Cholinesterase
inhibitors are cognitive enhancers used in the treatment of Alzheimer’s
disease and some other major neurocognitive disorders. Selective
serotonin reuptake inhibitors are used in the treatment of major
depression and a wide variety of anxiety disorders.
46. a, creatine kinase (Chapter 20)

This patient has developed neuroleptic malignant syndrome, a
potentially life-threatening complication of treatment with
antipsychotics. The syndrome includes autonomic instability
(hyperthermia, diaphoresis), motor abnormalities (rigidity, mutism),
and behavioral changes (delirium). Her primary risk factor is the rapid
antipsychotic dose escalation. Dehydration resulting from the
breakdown of her air conditioner may also be a risk factor. The
laboratory finding of a grossly elevated creatine kinase level is a
prominent feature of neuroleptic malignant syndrome. In addition,
white blood cell count is frequently elevated, liver enzymes are
typically elevated, and serum iron is reduced. Treatment is supportive
and involves immediate discontinuation of the antipsychotic. In
addition, dantrolene (treats skeletal muscle rigidity by blocking
intracellular calcium) and agents that increase dopamine (amantadine)
or dopamine agonists (bromocriptine) may be used.
47. a, appreciating the nature of his illness (Chapter 14)

This patient’s lack of insight into his mental illness results in inability to
understand the nature of his illness. Capacity is defined as a patient’s
ability to make a decision (positive or negative) regarding treatment.
This requires the demonstration of four elements: (1) understanding
the nature of one’s illness; (2) appreciation of the risks, benefits, and
alternatives to the proposed treatment; (3) ability to rationally
manipulate information (reason); and (4) ability to communicate a
choice.
48. d, primary polydipsia (Chapter 1)

The patient presents with seizure that is most likely a result of acute
hyponatremia. The hyponatremia could have many causes. The
syndrome of inappropriate antidiuretic hormone secretion, which is
often associated with oat cell carcinoma of the lung, is an unlikely
cause of the hyponatremia in a nonsmoker with a normal chest
radiograph. Clozapine can cause seizures and may be a contributing
factor to the seizure but would not cause hyponatremia. Hypertension
can lead to cerebral dysfunction but not usually seizures. This level of
mild hypertension would not have neurologic effects. Serotonin
syndrome can cause confusion but does not cause seizures or
hyponatremia. The diagnosis of exclusion would likely be polydipsia
and is suggested by the staff person reporting her excessive cola
drinking.
49. b, panic disorder (Chapter 4)

This patient has untreated panic disorder with a relatively late onset of
the disorder. She has a family history of agoraphobia, a complication
of panic disorder that this patient has developed. Her clinical history is
not consistent with major depression. Her anxiety comes in classic
waves of panic, not the constant worrying of a person with generalized
anxiety. She has neither the specific fear of spiders necessary to
diagnose arachnophobia nor the obsessions and compulsions of
obsessive-compulsive disorder.
50. e, discontinue dextroamphetamine therapy (Chapter 1)

The child has developed symptoms of mania and psychosis while in
the first few months of dextroamphetamine therapy for a presumed
case of attention-deficit disorder. The violence clearly warrants a
hospitalization. What is unclear, especially given the extensive family
history, is whether the symptoms are solely caused by treatment or if
the patient is having an initial episode of bipolar disorder or
schizophrenia. The diagnosis is unclear, but the first thing that should
be done is discontinuation of the dextroamphetamine. Further
treatment might include either an antipsychotic or a mood stabilizer.
An antidepressant would be contraindicated in a patient without
depression or anxiety who may be having a manic or psychotic
episode. Group therapy would be helpful after the acute stabilization
but is not the first step in management.
51. c, try to separate the couple and talk to the woman alone
(Chapter 13)
Patients suffering from abuse sometimes appear for treatment with
their abusers. This couple may have alcohol use disorder, given the
presence of an alcohol smell on their breath without evidence of
intoxication, a potential sign of high alcohol tolerance. Your primary
fiduciary responsibility is to your patient. Abused people may be afraid
to confront their abusers because of fear of retaliation. Therefore, it
would not be appropriate to call the police or to confront the suspected
abuser without more information. If you try to get more information
with the alleged abuser present, you may arouse suspicion in the
abuser who may then take the abused patient and leave. Finally,
calling around in an investigative mode violates patient confidentiality
and is outside the role of a physician treating a patient. The best
option is to find a tactful way to speak with the patient alone to ask
about potential abuse. With this approach, you preserve your patient’s
right to privacy, do not risk your intervention resulting in more harm to
the patient, and provide a safe opportunity for the patient to seek help
from a physician.
52. d, thiamine (Chapter 10)

This patient is exhibiting anterograde amnesia and confabulation,
which are typical signs of Korsakoff psychosis (alcohol-induced major
neurocognitive disorder, amnestic confabulatory type). This is a
consequence of thiamine deficiency, which is caused by alcohol
dependence. The thiamine-deficient patient initially develops
Wernicke’s encephalopathy, which is a triad of nystagmus, ataxia, and
mental confusion. If this is not reversed immediately with intravenous
thiamine repletion, many patients will progress to develop Korsakoff’s
psychosis, which is irreversible in two-thirds of cases. B12 deficiency
causes megaloblastic anemia and peripheral neuropathy caused by
demyelination of the dorsal columns and corticospinal tracts. Folic
acid deficiency causes macrocytic anemia. Niacin deficiency results in
pellagra with dermatitis, diarrhea, and dementia. Vitamin E deficiency
can cause ocular signs followed by long-tract signs such as muscle
weakness.
53. d, major frontotemporal neurocognitive disorder (Pick’s

disease) (Chapter 9)
This patient has developed the insidious onset of cognitive decline,
encompassing the prominent feature of marked personality change.
She is disinhibited, resulting in an inability to observe typical social
mores. The early age of onset of a major neurocognitive disorder,
family history of early-onset dementia, and prominent frontal and
temporal atrophy on neuroimaging are all consistent with the
diagnosis of major frontotemporal neurocognitive disorder (Pick’s
dementia). Major neurocognitive disorder due to Alzheimer’s disease
typically presents after age 65 with insidious onset of short-term
memory impairment. Major neurocognitive disorder due to HIV
infection (HIV-related dementia) presents as global cognitive decline
usually in the late stages of AIDS. Major neurocognitive disorder due
to Huntington’s disease (Huntington’s dementia) presents with other
typical features of Huntington’s disease including early onset (typically
during the mid-30s) and choreiform movements with prominent
caudate atrophy on neuroimaging. Major vascular neurocognitive
disorder (vascular dementia) typically presents with stepwise cognitive
decline in the setting of cardiovascular and cerebrovascular risk
factors. There may be focal findings on neurologic examination, and
neuroimaging typically shows multiple areas of pathology.
54. e, hopelessness (Chapter 13)

Among all the factors listed, hopelessness has been shown to be one
of the most reliable indicators of long-term suicide risk. Major
depression and other mood disorders and substance abuse disorders
are also risk factors for suicide.
55. b, dependent personality disorder (Chapter 11)

This patient appears to have a profound yearning for connection and a
dependent relationship with his elderly mother. He overly depends on
his mother to steer his life, including making minor decisions. He likely
fears abandonment by the mother on whom he depends, but he differs
from those with borderline personality disorder in that he has a more
stable sense of self and is not impulsive and self-destructive. His self-
esteem is not impaired, and he lacks the grandiosity that would be
seen in a person with narcissistic personality disorder. Although the
patient works in an often-solitary job, he is not an aloof, detached
loner with schizoid personality disorder. Also, there is no evidence of
the magical thinking that would characterize schizotypal personality
disorder.
56. a, schizophrenia (Chapter 1)

A diagnosis of schizophrenia requires a greater-than-6-month period
of positive and negative symptoms of psychosis combined with social
and occupational deterioration. Bipolar disorder requires the presence
of at least one episode of mania and usually consists of cycles of
mania and depression. Psychosis is common in the manic phase of
bipolar illness, but this patient does not display symptoms of mania
(i.e., pressured speech, decreased sleep, increased energy, etc.).
Major depression may be associated with psychosis, but this patient
does not provide evidence of having major depression. Alcohol
misuse can lead to psychosis, especially auditory hallucinosis, but
other symptoms of alcohol misuse would be present. Paranoid
personality disorder does not lead to the level of severe social and
occupational dysfunction experienced by this patient.
57. b, medication-induced akathisia (Chapter 20)

Akathisia is most commonly caused by antipsychotic medications,
particularly typical antipsychotics (neuroleptics). Akathisia produced
by drugs in the selective serotonin reuptake inhibitor class is less
likely, but these medications are so widely used and are prescribed by
so many nonpsychiatric physicians, that this important side effect may
be misdiagnosed. Akathisia is profoundly distressing to some patients,
and in some cases, it leads to attempted or successful suicide. It is
easily treatable by removing the offending agent in most cases.
Adding β-blockers and benzodiazepines is also helpful.
58. c, drug toxicity (Chapter 17)
The best explanation for the patient’s condition at the moment is drug
toxicity resulting from elevated carbamazepine levels. The patient
displays known symptoms consistent with carbamazepine toxicity. The
clue to making the diagnosis rests with the sequence of events. The
patient likely was noncompliant with his medications as an outpatient,
leading to reduced levels of mood stabilizer and a manic break. On
admission, he was restarted at his usual outpatient doses, which
presumably provide a therapeutic drug level when taken as
scheduled. Then, an antibiotic is added. We are not provided with the
name of the drug, but it is important to remember that some
antibiotics, such as macrolide or fluoroquinolone antibiotics, may
inhibit the metabolism of medications metabolized by the liver’s
cytochrome P450 enzyme system.
59. e, informed consent is not necessary (Chapter 14)

This clinical scenario would be considered a true emergency, and
performing a tracheotomy to stabilize the patient’s airway would not
require informed consent. Commitment is not necessary or
appropriate in this circumstance. If this were not an emergency
situation, each of the other issues would be a valid concern.
60. c, dialectical behavioral therapy(Chapter 21)

The patient described has borderline personality disorder. Dialectical
behavioral therapy was developed specifically for the treatment of
borderline personality disorder. Patients with borderline personality
disorder often require adjunctive treatments for their substance abuse,
mood disorders, and other comorbidities. Because of their specific use
of defense mechanisms that are considered primitive, they are
generally not good candidates for long-term psychodynamic
psychotherapy.
61. c, atomoxetine and behavioral therapy (Chapter 19)

The child described meets the criteria for attention-deficit/hyperactivity
disorder (ADHD), which is generally managed with psychostimulants.
Methylphenidate is the first-line agent followed by d-amphetamine.
These are sometimes avoided because of bizarre behavior or long-
term physical effects such as weight loss and inhibited body growth.
Alternatively, children can be treated with atomoxetine, a drug that
selectively inhibits the norepinephrine reuptake transporter. Because
dopamine in the prefrontal cortex is cleared by the norepinephrine
reuptake transporter, inhibition of the transporter by atomoxetine leads
to increased prefrontal synaptic dopamine. Alpha-2 receptor agonists
like clonidine and guanfacine can also be used either in addition to a
stimulant or by themselves if stimulants are not tolerated. Behavioral
management is also one of the mainstays of treatment for ADHD.
62. b, neuroleptic malignant syndrome (Chapter 20)

Neuroleptic malignant syndrome can occur at any time during the use
of antipsychotic medications. It is most frequently seen during periods
of dehydration or rapid escalation of dose. Serotonin syndrome can
present similarly to neuroleptic malignant syndrome but usually has
less muscular rigidity. Dystonia is a neuroleptic-induced movement
disorder characterized by muscle spasms. Akathisia consists of a
subjective sensation of inner restlessness or a strong desire to move
one’s body. Disulfiram serves to prevent alcohol ingestion through the
fear of the consequences of its interaction with the metabolism of
alcohol. Disulfiram blocks the oxidation of the acetaldehyde, which
leads to flushing, headache, sweating, dry mouth, nausea, vomiting,
and dizziness.
63. d, to order a thorough medical and neurologic workup

(Chapter 2)
This patient displays the key symptoms necessary for the diagnosis of
an acute manic episode. The onset of bipolar disorder in someone of
this age group with no prior psychiatric history is unlikely, however.
Therefore, medical and neurologic causes of the patient’s behavioral
change should be carefully assessed. A mood stabilizer or
antipsychotic medication may be needed now or at a later point for
symptom control but would not be started for the specified diagnoses
until a definitive workup is completed. An antidepressant would not
help treat this symptom complex and might make the condition worse.
The patient does have symptoms consistent with hyperthyroidism, but
the treatment would not be to add more thyroid hormone.
64. d, decreased stage 4 sleep (Chapter 12)

Objective evidence from sleep studies conducted on people with
depression has revealed that deep sleep (delta sleep, stages 3 and 4)
is decreased in depression. There are also rapid eye movement
(REM) sleep alterations including increased time spent in REM and
earlier onset of REM in the sleep cycle (decreased latency to REM).
65. e, obsessive-compulsive personality disorder (Chapter 11)

The essential feature of obsessive-compulsive personality disorder
(OCPD) is a preoccupation with orderliness, perfectionism, and mental
and interpersonal control, at the expense of flexibility, openness, and
efficiency. This pattern begins by early adulthood and is present in a
variety of contexts. Despite the similarity in names, obsessive-
compulsive disorder (OCD) is usually easily distinguished from OCPD
by the presence of obsessions and compulsions as well as on the
basis of symptom severity. Obsessions may consist of aggressive
thoughts and impulses, fears of contamination by germs or dirt, or
fears of harm befalling someone. Compulsions such as washing,
checking, or counting are rituals with the purpose of neutralizing or
reversing the fears. People with OCPD are usually self-critical,
whereas those with narcissistic personality disorder are more likely to
believe that they have achieved perfection. Individuals with schizoid
personality disorder lack a fundamental capacity for intimacy.
Individuals with antisocial personality disorder repetitively disregard
the rules and laws of society. They are exploitive and rarely
experience remorse.
66. d, schizophrenia (Chapter 1)

Panic disorder with a panic attack might cause a disturbance in a
public place, but odd accusations, disordered speech, and other signs
of paranoia would not be present. Heroin intoxication usually presents
with a quiet, sedated condition, with decreased heart rate and
respirations. Paranoia is also not usually a component of heroin
intoxication. Attention-deficit/hyperactivity disorder might present with
excessive motor activity but, again, paranoia, pressured speech, and
agitation are not consistent with this condition. Schizophrenia is
associated with agitation, disorganized speech, paranoia, and
disheveled appearance. Therefore, this is the best diagnostic choice
among the provided options. Hypothyroidism generally presents with
apathy, depression, and psychomotor retardation, if severe.
Hyperthyroidism might mimic some of the patient’s symptoms, such as
pressured speech or agitation. Of note, there is not sufficient evidence
provided in this vignette to make a formal diagnosis of schizophrenia.
The time course of the patient’s illness, reversible medical causes,
drug-induced paranoia, and other psychiatric conditions (such as
schizoaffective disorder, mania with psychosis, or depression with
psychosis) should all be carefully considered.
67. e, with rapid cycling (Chapter 2)

The rapid cycling specifier can be applied to bipolar I or bipolar II
disorder. It is defined as at least four episodes of a mood disturbance
in the previous 12 months that meet criteria for a major depressive,
manic, mixed, or hypomanic episode. A specification of catatonic
features can be applied to a current major depressive, manic, mixed,
or hypomanic episode if the patient demonstrates at least two of the
following signs: motoric immobility, excessive motor activity, mutism,
echolalia, or voluntary assumption of inappropriate or bizarre
postures. Atypical features refer to patients who demonstrate mood
reactivity and significant weight gain, hypersomnia, or leaden paralysis
during their mood episode. Peripartum refers to the onset of an
episode during pregnancy or within 4 weeks postpartum. In order to
diagnose a patient with the seasonal pattern specifier, there has to
have been a regular temporal relationship between the onset of the
major depressive episode and a particular time of year. This patient
had depressive episodes in both winter and fall.
68. e, capacity (Chapter 14)

The three elements commonly recognized in informed consent include
information, capacity, and consent. Information is the content of the
proposed treatment and the alternatives to treatment, including
potential effects of failing to treat. Capacity requires that a person
possess the ability to understand, appreciate, reason, and express a
choice. This patient has expressed a choice but would need to show
evidence of understanding, appreciation, and reasoning to fully
demonstrate all elements of capacity. Consent must be given
voluntarily, namely, must not involve subtle or overt coercion.
69. d, industry versus inferiority (Chapter 21)

The boy is struggling with Erikson’s life cycle known as industry
versus inferiority. Between the ages of 5 and 13, children struggle with
developing a sense of self on the basis of the things that they create.
Caregivers provide for a sense of mastery by teaching and giving
feedback. In this case, the child is struggling with what his
performance on the soccer field implies about his general worthiness.
The father is teaching and guiding his son in the sport, which is
undoubtedly promoting the son’s psychological development. Intimacy
versus isolation, answer a, occurs later in development in young
adulthood. Identity versus role confusion occurs just after identity
versus inferiority and corresponds to adolescence. Initiative versus
guilt precedes identity versus inferiority at ages 3 to 5 and involves the
feelings of guilt that ensue when a child first has enough autonomy to
explore the world, including things that the parents may find
disturbing. Finally, ego integrity versus despair involves late-life
acceptance of one’s place in the life cycle versus regret of unfulfilled
earlier life desires.
70. a, body dysmorphic disorder (Chapter 6)

The patient holds a perception that her nose is crooked, and therefore
ugly, which does not appear to be true. This is body dysmorphic
disorder. She is extremely preoccupied with this perceived problem in
her physical appearance to the point that she has sought surgical
remediation. The patient does not gain satisfaction from showing her
body to others as in exhibitionism. Although many clinicians may find
themselves feeling annoyed with her preoccupation, she does not
have the other clinically troubling features of a person with borderline
personality disorder. She does feel scrutinized in public places, which
suggests social phobia, but her feelings are only in relation to her
perception that her nose is crooked. Finally, people with posttraumatic
stress disorder have anxiety and present in emergency rooms with
nonspecific distress but do not have a preoccupation with a particular
part of their body.
71. b, major frontotemporal neurocognitive disorder (Chapter 9)

Although there can be a large amount of overlap of symptoms
between major neurocognitive disorder due to Alzheimer’s disease,
major frontotemporal neurocognitive disorder (Pick’s disease), and
major vascular neurocognitive disorder, major frontotemporal
neurocognitive disorder is generally characterized by an onset of
personality change and a decline in function at work and home.
Imaging studies and presentation help make the diagnosis. At
autopsy, the differences are readily apparent on pathologic review.
Major frontotemporal neurocognitive disorder is marked by “Pick’s
bodies,” and neurons have a ballooned appearance. This is not seen
in Alzheimer’s disease, which is characterized by the plaques and
tangles. Major vascular neurocognitive disorder is more commonly
characterized by either multiple cortical infarcts, subcortical small
vessel disease, or strategically placed infarcts. Pick’s disease is also
typically restricted to the frontal and anterior temporal lobes.
Huntington’s chorea generally presents with a movement disorder
followed by emotional lability or depression, and then dementia. Prion
disease of the Creutzfeldt–Jakob variant presents with the clinical triad
of myoclonus, dementia, and abnormal electroencephalogram results.
Spongiform encephalopathy is present at autopsy.
72. b, psychoanalytic psychotherapy (Chapter 21)

The patient was likely undergoing some kind of psychoanalytic
psychotherapy. The focus on early childhood and the multiple
sessions per week are common features of this type of therapy. The
focus on relationships indicates that the therapist may have been
using object-relations theory, a common form of psychoanalysis, to
guide the treatment. If it were cognitive-behavioral therapy, the focus
would have been on more present-day thoughts and their impact on
feelings. Interpersonal therapy is a short-term therapy that focuses on
specific aspects of present-day relationships. Behavior therapy uses
behavioral principles of reinforcement and aversion to effect specific
behavioral changes (e.g., losing weight, quitting smoking). Finally,
dialectical behavior therapy is another therapy that focuses on
present-day thoughts and feelings to help patients with borderline
personality disorder to manage intolerable feelings and decrease self-
destructive behaviors.
73. d, naltrexone (Chapter 19)

The medication is probably naltrexone. Naltrexone has been shown to
decrease frequency and intensity of alcoholic relapse. It also does not
cause illness when alcohol is consumed with it as does disulfiram
(Antabuse). An additional medication approved for treating alcohol
dependence/alcohol use disorder is acamprosate. Zolpidem is a
nonbenzodiazepine sleep aid, buspirone is a nonbenzodiazepine
anxiolytic, and metoclopramide is a medication that is approved for
gastroesophageal reflux disease and is also used off-label for
migraines.
74. a, oxazepam (Chapter 18)

Lorazepam, oxazepam, and temazepam are benzodiazepines
metabolized primarily by conjugation and do not have active
metabolizes. Clonazepam is a long-acting benzodiazepine, but it does
not have long-acting metabolites. Diazepam and chlordiazepoxide are
metabolized mainly by glucuronidation and have long-acting
metabolites. Thus, these two medications are prone to accumulate in
individuals with impaired hepatic metabolism and may cause
benzodiazepine toxicity. Buspirone is not a benzodiazepine and is not
used for alcohol detoxification.
75. b, major vascular neurocognitive disorder (Chapter 9)

The patient has multiple risk factors for vascular-related
dementia/neurocognitive disorder, including cigarette smoking,
hypercholesterolemia, hypertension, type 2 diabetes mellitus, and
coronary artery disease. Patients with these risk factors often show
nonspecific brain white matter disease on MRI and should have
slowed progression of neurocognitive impairment if treated for the
underlying risk factors. Huntington’s disease is an autosomal
dominant inheritance; Creutzfeldt–Jakob’s disease is prion linked;
Parkinson’s disease is caused by degeneration in monoamine and
other brain neurons; major neurocognitive disorder due to HIV
infection is associated with exposure to the HIV virus.
76. e, obstructive apnea hypopnea (Chapter 12)

Obstructive apnea hypopnea is a sleep disorder characterized by
disordered breathing during sleep that results in frequent awakening
and fragmentation of nighttime sleep with resultant daytime
sleepiness. The patient’s syndrome complex is consistent with
obstructive apnea hypopnea, a type of breathing-related sleep
dysfunction consisting of recurrent episodes of apnea while sleeping.
The presence of loud snoring and choking or gasping during sleep is a
cardinal sign of this condition.
77. d, barbiturates (Chapter 10)

Barbiturate withdrawal can be fairly dangerous and can include
hyperpyrexia, seizure, and potentially death. Withdrawal from crack
cocaine, crystal methamphetamine, and marijuana is generally self-
limited. Occasionally, the patient can appear psychotic during
intoxication with these agents. Withdrawal from crack cocaine and
crystal methamphetamine is generally characterized by fatigue,
depression, nightmares, headache, sweating, muscle cramps, and
hunger. Nicotine withdrawal is characterized by irritability, fatigue,
insomnia, and difficulty concentrating.
78. c, naloxone (Chapter 19)

Suboxone is the brand name for the combination of buprenorphine
with naloxone. Buprenorphine, a partial opioid agonist, reduces illicit
opioid use with long-term therapy. Naloxone is an opioid antagonist
that has poor oral absorption. When used alone, buprenorphine does
have the potential to be abused as an injectable agent. When
buprenorphine is combined with naloxone, however, it will cause
withdrawal when given parenterally. Flumazenil is a benzodiazepine
receptor antagonist. Acamprosate is a glutamate receptor modulator
used for the maintenance of alcohol abstinence. Methadone is a long-
acting opiate agonist used in methadone maintenance treatment for
opiate dependence.
79. b, conversion disorder (Chapter 12)

The essential feature of conversion disorder is the presence of
symptoms or deficits affecting voluntary motor or sensory function that
suggest a neurologic or other general medical condition. Conversion
symptoms are related to voluntary motor or sensory functioning and
are thus referred to as “pseudoneurological.” Motor symptoms or
deficits include impaired coordination or balance, paralysis or localized
weakness, aphonia, difficulty swallowing or a sensation of a lump in
the throat, and urinary retention. Sensory symptoms or deficits include
loss of touch or pain sensation, double vision, blindness, deafness,
and hallucinations. A diagnosis of conversion disorder should be
made only after a thorough medical investigation has been performed
to rule out a neurologic or general medical condition. There are
typically psychological factors or stressors associated with the
symptom or deficit. The symptoms are not intentionally produced as in
factitious disorder. Illness anxiety disorder is a condition involving
preoccupation with having a serious disease that appears to be based
on a misinterpretation of bodily function and sensations. Body
dysmorphic disorder is a somatic symptom and related disorder
characterized by excessive concern regarding an imagined or
perceived defect in appearance.
80. e, antisocial personality disorder (Chapter 11)

This patient exhibits a pervasive pattern of flagrant disregard for the
rules and laws of society. A childhood history of severe neglect or
abuse is common. Despite the report of a childhood trauma, a
diagnosis of posttraumatic stress disorder is not made unless there is
hyperarousal, intrusive recollection of the trauma, and efforts to avoid
recollection of the trauma. His denial of mood disturbance and lack of
either prior hospitalizations or family history makes both bipolar
disorder and cyclothymic disorder unlikely. This patient may have
been diagnosed with conduct disorder in childhood. When conduct
disorder behavior persists into adulthood, the diagnosis becomes
antisocial personality disorder.
81. d, Tourette’s disorder (Chapter 8)

Tourette’s disorder is characterized by involuntary vocal and motor
tics. Sometimes, the vocal tics are grunts or barks, but they can
develop into word tics. Tourette’s disorder is more common in young
males (2–4:1 male–female ratio) and onset is usually in late
adolescence but before age 18. Adolescent rebellion is a colloquial
term for certain types of teenage behavior but does not explain vocal
and motor tics. Schizophrenia is not likely because this young man
does not have psychotic symptoms. Substance use can produce a
behavioral change in an individual, but vocal and motor tics are not
classic. Conduct disorder is diagnosed when a child consistently
violates the basic rights of others and ignores societal rules and
norms. A child suspected of having Tourette’s disorder should have a
careful medical and neurologic evaluation. Wilson’s disease and
Huntington’s disease both present with movement disturbance that
could be confused with motor tics and therefore need to be ruled out,
and an electroencephalogram should be performed to assess for
seizure disorder.
82. c, haloperidol (Chapter 15)

Vilazodone and desvenlafaxine are medications used mainly for the
treatment of depression. Lamotrigine is an antiepileptic medication
and mood stabilizer that has efficacy in treating bipolar depression.
Atomoxetine is a selective inhibitor of the norepinephrine reuptake
transporter that is approved for the treatment of ADHD. Low doses of
high-potency antipsychotics are a common treatment for tics in
Tourette’s disorder. These include haloperidol and pimozide, among
others.
83. d, hoarding disorder (Chapter 6)

The patient displays classic symptoms consistent with hoarding
disorder. Hoarding disorder is classified as an obsessive-compulsive
and related disorder in DSM 5. This condition is diagnosed when a
person has great difficulty letting go of possessions, even those that
others would consider worthless or trash. In hoarding disorder, the
accumulation of objects can lead to severe cluttering of living areas
and can become dangerous if stacks are too high, for example, or if
they create a fire hazard. Distress at attempting to discard
possessions is a cardinal feature. Excoriation disorder is a condition in
which an individual repeatedly picks at his or her skin, producing
areas of excoriation. Trichotillomania is a condition in which an
individual repeatedly pulls out his or her hair, despite attempts to stop.
Obsessive-compulsive disorder is characterized by the presence of
obsessions and compulsions, which are not prominent in this patient
aside from the compulsion to keep objects of minimal worth and value.
Kleptomania is a condition in which an individual repeatedly steals
objects, with the primary purpose being to steal the object and not
because it is needed for use. Before the theft, individuals with
kleptomania develop tension and anxiety that is relieved by the act of
stealing.
84. b, delayed ejaculation (Chapter 12)

Delayed ejaculation is a sexual dysfunction that is diagnosed when a
man has a marked delay in achieving ejaculation/orgasm or a
complete inability to do so. This may cause distress for the man and
his sex partner. Delayed ejaculation may be lifelong, starting once
someone begins being sexually active, or acquired, occurring after a
period of time in which there is not an ejaculatory delay or inability. In
this patient, the history suggest that the condition has been acquired.
Male hypoactive sexual desire disorder is diagnosed when someone
has a period of over 6 months in which his desire for sexual activity
and his fantasies and sexual thoughts are absent or markedly lower
than might be expected. There is no evidence from this patient to
suggest substance/medication-induced sexual dysfunction although
delayed ejaculation can be a common side effect to some
medications, including selective serotonin reuptake inhibitors (SSRIs).
Erectile disorder is characterized by difficulty in achieving or
maintaining an erection, which is not present in this patient. Priapism
is a serious condition in which an erection of the penis or clitoris is
sustained for a very long period, often for several hours. Priapism can
occur in response to medical illnesses, such as sickle cell disease, or
as medication side effect, for example, due to trazodone.
85. d, opioid use disorder (Chapter 10)

Several items in this patient’s history point to the presence of an
opioid use disorder. Intermittent periods of excessive opioid use are
characterized by patients appearing sleepy, drugged, and difficult to
arouse. In many cases, excessive use, especially of long-acting or
intravenous opioids can lead to respiratory arrest and death. At other
times, individuals may have periods of withdrawal when they can no
longer obtain the drug and may display extreme dysphoria, agitation,
and irritability. It is common for patients to seek jobs or social
associations, such as caring for elderly family members or working in
medically related fields that place them in a position to obtain their
desired drug. History provided by family and friends is often highly
revealing in this regard. The patient displays some episodes of
irritability and agitation, which can be seen in borderline personality
disorder, but there is no evidence for other symptoms suggestive of
this condition. Intermittent explosive disorder is characterized by
periods of intense anger with verbal aggression or may include
property damage or assault to others. Dysphoric mood and irritability
can be seen in major depressive disorder but the patient does not
reveal other symptoms of this condition. Substance-induced mood
disorder could be considered in the differential diagnosis, but the
patient is not reporting depressed or elevated mood.
86. a, schizophreniform disorder (Chapter 1)

This patient presents with psychotic symptoms and agitation. Until
further history is obtained or future episodes are observed, the
diagnosis is uncertain. This could be a so-called “first break” of
schizophreniform disorder that may persist for the required 6 months
to meet the criteria for schizophrenia or it could be a brief psychotic
disorder if symptoms last for less than 1 month. It might be a manic
episode with psychotic features in a patient with underlying bipolar
disorder or schizoaffective disorder. The psychosis may also be
substance induced (e.g., amphetamine-induced psychotic disorder).
Although patients with generalized anxiety disorder can present with
restlessness or irritability, they are usually not agitated and do not
have auditory hallucinations or thought disorder. Patients with winter
depression and atypical depression usually present with symptoms of
decreased energy, increased appetite, and increased sleep. They also
complain of psychomotor slowing. Individuals with obsessive-
compulsive disorder have unreasonable obsessions and compulsions.
87. c, modeling (Chapter 21)

Modeling is learning based on observing others and mimicking their
actions. Classical conditioning is learning in which a neutral stimulus is
paired with a natural stimulus, with the result that the previously
neutral stimulus alone becomes capable of eliciting the same
response as the natural stimulus. Operant conditioning is a form of
learning in which environmental events influence the acquisition of
new behaviors or the extinction of existing behaviors. Projection and
regression are both defense mechanisms.
88. c, frotteurism (Chapter 12)

The essential features of a paraphilia are recurrent, intense sexually
arousing fantasies, sexual urges, or behaviors generally involving (1)
nonhuman objects, (2) the suffering or humiliation of oneself or one’s
partner, or (3) children or other nonconsenting persons that occur over
a period of at least 6 months. Frotteurism is sexual excitement derived
by rubbing one’s genitals against or by sexually touching a
nonconsenting stranger. Exhibitionism is a paraphilia in which a
person derives sexual excitement from exposing one’s genitals to a
stranger. In fetishism, sexual arousal is derived from nonliving objects.
In pedophilia, sexual excitement is derived in fantasy or behavior
involving sex with prepubescent children. In voyeurism, sexual
excitement is derived from fantasy or behavior involving the
observation of unsuspecting people undressing, naked, or having sex.
For paraphilias, the diagnosis is made if the person has acted on
these urges or if the urges or sexual fantasies cause marked distress
or interpersonal difficulty.
89. c, transvestic disorder (Chapter 12)

Transvestic disorder is diagnosed when a person reports cross-
dressing behaviors that produce sexual arousal and that cause
clinically significant distress. This patient is representative of
individuals with this condition and the behavior can cause a great deal
of shame and suffering, along with relationship discord if a person is
partnered. In voyeuristic disorder, a person derives sexual excitement
from the thought or action of observing someone (who is unaware that
he or she is being observed) undressing, naked, or having sex.
Exhibitionistic disorder is a condition in which a person is sexually
aroused by the thought and act of exposing one’s genitals to a
nonconsenting person. In sexual masochism disorder, individuals
derive sexual arousal from physical restraint, humiliation, being
beaten, or other forms of suffering. In sexual sadism disorder, a
person derives sexual arousal from producing suffering in another
person, either through physical means or psychological means.
90. e, anorexia nervosa (Chapter 7)

This patient has the classic signs and symptoms of anorexia nervosa,
in which a person, usually female, engages in activities that lead to
weight loss and a low BMI. This patient engages in food restriction
and purging by inducing vomiting. Other methods for purging may
include the use of enemas or laxatives. Anorexia is diagnosed when
one’s BMI is below 17 kg/m2 and severity of this disorder is based on
BMI. In this case, the patient has severe anorexia nervosa. Major
depression is often comorbid with anorexia and can lead to reduced
appetite and weight loss but we do not have evidence for prominent
symptoms of major depression from the patient’s history. Rumination
disorder is characterized by repeated regurgitation of food after eating
that is not due to a medical condition. In avoidant/restrictive food
intake disorder, a person simply does not eat, either due to disinterest
in food or a sense that eating is unpleasant but there are not purging
activities. In bulimia nervosa, individuals engage in out-of-control
binge eating followed by purging behaviors but weight is usually
normal or elevated. In both anorexia nervosa and bulimia nervosa,
patients display body image concerns.
91. c, psychotherapy once medical condition has stabilized

(Chapter 7)
The management of anorexia nervosa is initially directed at the
presenting symptoms. When medical complications are present, these
must be carefully treated and followed. During starvation,
psychotherapy is of little value because of the cognitive impairment
produced by starvation. When less medically ill, a therapeutic program
including supervised meals; weight and electrolyte monitoring;
psychoeducation about the illness, starvation, and nutrition; individual
psychotherapy; and family therapy can begin. The most efficacious
treatments for the disorder are family-based treatment (FBT) and
adolescent-focused treatment (AFT). Psychotropic medications such
as selective serotonin reuptake inhibitors (SSRIs) have little or no
effect on anorexia per se but are used to treat comorbid psychiatric
illness. Bupropion and atomoxetine can produce weight loss, and
bupropion is associated with increased seizure risk, so they are not
appropriate considerations.
92. c, lisdexamphetamine (Chapter 19)

The patient in question has symptoms consistent with binge eating
disorder, in which binge eating without attempts to compensate for the
binge are predominant. Binges are characterized by eating more
rapidly than normal, eating until uncomfortably full, eating large
amounts when not hungry, feeling embarrassed due to the amount
eaten, or feeling disgusted/depressed/guilty afterward. In addition, the
individual must be distressed by the behavior. Patients are self-
conscious about their binges and attempt to conceal this behavior.
Olanzapine and lurasidone are atypical antipsychotics that might
increase appetite and potentially exacerbate the patient’s weight gain.
Valproic acid and phenytoin are antiepileptic medications, and
valproate is used as a mood stabilizer in bipolar disorder.
Lisdexamphetamine is a psychostimulant that is approved for the
treatment of binge eating disorder. Other medications in the
psychostimulant class may have similar efficacy.
93. c, ventral striatum/nucleus accumbens (Chapter 10)

Addictive substances act by a final common pathway influencing the
medium spiny GABAergic neurons of the ventral striatum/nucleus
accumbens. Addictive behaviors such as overeating, gambling, sex,
and possibly Internet use also engage this final common pathway. The
ventral striatum/nucleus accumbens is a target of the
mesocorticolimbic dopamine pathway that mediates reward system
function. The cerebellum may have secondary role in addiction but is
not a primary participant. The suprachiasmatic nucleus is mainly
involved in entraining circadian rhythms. The pulvina nucleus is a
thalamic nucleus having roles in visual salience and may be related to
altered salience in addiction. The mammillary bodies of the
hypothalamus can be damaged from alcohol use and thiamine
depletion but have a primary role in memory.
94. d, social anxiety disorder (Chapter 4)

The patient displays symptoms consistent with social anxiety disorder
(social phobia). Social anxiety disorder is an anxiety disorder in which
patients have an intense fear of being scrutinized in social or public
situations (e.g., giving a speech, speaking in class). The disorder may
be generalized or limited to performance situations. Public speaking
anxiety is the most common form of performance-related social
anxiety disorder. Agoraphobia is a disabling condition characterized
by an intense fear of places or situations in which escape might be
difficult (or embarrassing). Generalized anxiety disorder is not limited
to social situations but consists of widespread anxiety and tension
about a broad range of concerns. Panic disorder is characterized by
recurrent, unexpected panic attacks. Social anxiety disorder has
considerable symptom overlap with avoidant personality disorder, but
does not share the dependent and needy characteristics of dependent
personality disorder.
95. d, gender dysphoria (Chapters 8 and 12)
While gender dysphoria remains a controversial diagnosis in
psychiatry, this child displays the characteristic concerns of this
condition. While an incongruity between one’s biologic gender and
one’s gender identity is not considered a psychiatric diagnosis, this
child’s distress in relation to gender identity is indicative of gender
dysphoria. Often, these individuals will pursue hormonal therapy or
gender-reassignment surgery. Transvestic fetishism is diagnosed
when a person derives sexual pleasure and excitement from dressing
in clothing of the opposite gender. Adjustment disorder can occur in
response to specific events and can be associated with distress or
depressed or anxious mood, but there is no evidence for a single
precipitating event in this case. Illness anxiety disorder is
characterized by excessive concerns about one’s health or about
being ill.
96. c, illness anxiety disorder (Chapter 12)

This patient has a preoccupation with having a serious illness. He has
no particular symptoms to suggest a somatic symptom disorder and is
primarily worrying about his condition. His symptoms are not
consistent with avoidant personality disorder, in which individuals
avoid close social contacts. There is no particular event to suggest
that the patient is adjusting to something that occurred in his life, so
adjustment disorder is not likely. Generalized anxiety disorder is
characterized by generalized worry and somatic tension across a
broad range of topics. This patient is narrowly focused on being ill.
97. b, the hippocampus, fornix, and mammillary bodies (Chapter

10)
Alcohol-induced persisting amnestic disorder (now classified as a
major neurocognitive disorder), also known as Korsakoff’s psychosis,
is associated with damage to the hippocampus, fornix, and
mammillary bodies. Damage to these structures is thought to be
caused by thiamine deficiency. Confabulation (i.e., making up
information to fill gaps in memory) is common. Wernicke–Korsakoff’s
syndrome (classified as a neurocognitive disorder in DSM 5) may
develop in the patient with alcohol use disorder because of thiamine
deficiency. The acute Wernicke’s stage of the syndrome is also called
Wernicke’s encephalopathy. Wernicke’s encephalopathy consists of
the triad of eye movement abnormalities, ataxia, and mental
confusion; however, few patients with Wernicke’s syndrome display
the complete triad, and the diagnosis of Wernicke’s syndrome may be
missed in up to 90% of clinical presentations. The brain stem and
frontal lobes, thalamus and cingulate gyrus, caudate and putamen,
and cerebellum are not brain regions associated with amnestic
disorder in alcoholism.
98. d, admit to the inpatient unit for alcohol detoxification without

starting an antidepressant (Chapter 10)
This patient’s history, with no evidence for a depressive disorder
before initiating alcohol use, is most consistent with alcohol-induced
depressive disorder. The patient’s level of alcohol intake warrants
admission for inpatient detoxification to avoid serious life-threatening
sequelae of alcohol withdrawal, as does the patient’s suicidal ideation.
The patient should be monitored carefully for depressive symptoms
and suicidal ideation. In most cases, mood improves with alcohol
detoxification. The patient would benefit from referral to Alcoholics
Anonymous upon discharge after detoxification and if her suicidal
ideation has resolved, but is not appropriate for outpatient referral at
present. Bipolar disorder is frequently comorbid with substance use
disorder, but the patient’s history does not suggest this.
99. a, autism spectrum disorder (Chapter 8)

This patient exhibits the common features of a person with a
developmental disability. The social difficulties and getting lost in small
details while missing the big picture are common manifestations of
autism spectrum disorder. Although patients with autism spectrum
disorder may appear to avoid social contact, this is secondary to the
recurrent experiences of social rejection that are common for children
with this condition. Anxiety should always be ruled out, as should
posttraumatic stress disorder. Children with either condition can be
quite withdrawn and socially awkward. There is no evidence provided
for intellectual disability or traumatic events predisposing to
posttraumatic stress disorder.
100. a, lithium toxicity (Chapter 17)

Because lithium is renally cleared, its serum level can be affected by
states of dehydration or renal insufficiency. Signs of lithium toxicity,
including coarse tremor, confusion, ataxia, and diarrhea, are evident in
this patient. Although oxcarbazepine toxicity can similarly result in
ataxia and confusion, it is not associated with coarse tremor or
diarrhea. Oxcarbazepine levels are also not as sensitive to levels of
dehydration. Fluoxetine can cause nausea, headache, restlessness,
insomnia, and anorgasmia. It is generally nontoxic even in overdose.
Serotonin syndrome can cause tremor and confusion but not ataxia.
101. e, ketamine (Chapter 16)

Emerging data have suggested that intravenous ketamine can acutely
reduce or resolve suicidality and depressed mood in some patients.
Given this patient’s history of treatment refractory depression,
ketamine may be an appropriate therapeutic consideration. Ketamine
is delivered over a slow intravenous infusion or an intravenous bolus
usually. The medication is under additional study as a potentially
powerful novel therapeutic for acutely reducing suicidality in the
emergency setting. Much more long-range follow-up is needed to
ascertain the duration of the effect on reducing suicidal ideation and
which patients are most likely to benefit from this treatment.
Aromatherapy, phototherapy, and vagal nerve stimulation may have
effects on depressed mood but have not been demonstrated to
acutely reduce suicidal ideation or depression. Melatonin may help
improve mood through improving sleep.
102. d, histrionic (Chapter 11)

This patient exhibits features of histrionic personality disorder. These
include attention-seeking and theatrical behaviors such as wearing
dramatic and seductive clothing and makeup, inappropriate flirtation,
and exaggerated emotional responses to events of little significance.
Patients with this diagnosis often believe that their relationships are
more significant than they actually are. Patients with antisocial
personality disorder disregard societal rules and lack a sense of
remorse. Avoidant personality disorder is associated with avoidance of
relationships resulting from feelings of inadequacy. Dependent
personality disorder is associated with extreme dependence on others
and fear of separation. Patients with schizoid personality disorder are
emotionally detached.
CHAPTER 1
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schizophrenia: the widening gap between basic and clinical neuroscience.
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Intervention Effectiveness (CATIE) Investigators. Effectiveness of
antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med.
2005;353(12):1209–1223.
Tandon R, Heckers S, Bustillo J, et al. Catatonia in DSM-5. Schizophr Res.
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CHAPTER 2
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the cage. Int J Bipolar Disord. 2017;5(1):35. doi:10.1186/s40345-017-
0104-6.
Phillips ML, Swartz HA. A critical appraisal of neuroimaging studies of
bipolar disorder: toward a new conceptualization of underlying neural
circuitry and a road map for future research. Am J Psychiatry.
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Liu B, Liu J, Wang M, et al. From serotonin to neuroplasticity: evolvement of
theories for major depressive disorder. Front Cell Neurosci. 2017;11:305.
Roy AK, Lopes V, Klein RG. Disruptive mood dysregulation disorder: a new
diagnostic approach to chronic irritability in youth. Am J Psychiatry.
2014;171:918–924.
Sepede G, Sarchione F, Matarazzo I, et al. Premenstrual dysphoric disorder
without comorbid psychiatric conditions: a systematic review of
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CHAPTER 4
Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders.
Dialogues Clin Neurosci. 2017;19(2):93–107.
Garakani A, Mathew SJ, Charney DS. Neurobiology of anxiety disorders and
implications for treatment [review]. Mt Sinai J Med. 2006;73:941–949.
Williams T, Hattingh CJ, Kariuki CM, et al. Cochrane pharmacotherapy for
social anxiety disorder (SAnD). Cochrane Database Syst Rev. 2017;
(10):CD001206.
CHAPTER 5
Brand BL, Sar V, Stavropoulos P, et al. Separating fact from fiction: an
empirical examination of six myths about dissociative identity disorder.
Harv Rev Psychiatry. 2016;24(4):257–270.
Hopper JW, Frewen PA, van der Kolk BA, et al. Neural correlates of
reexperiencing, avoidance, and dissociation in PTSD: symptom
dimensions and emotion dysregulation in responses to script-driven trauma
imagery. J Trauma Stress. 2007;20(5):713–725.
Jay EL, Sierra M, Van den Eynde F, et al. Testing a neurobiological model of
depersonalization disorder using repetitive transcranial magnetic
stimulation. Brain Stimul. 2014;7(2):252–259.
Mueser K, Gottlieb J, Xie H, et al. Evaluation of cognitive restructuring for
post-traumatic stress disorder in people with severe mental illness. Br J
Psychiatry. 2015;206(6):501–508. doi:10.1192/bjp.bp.114.147926.
Reinders AA, Willemsen AT, den Boer JA, et al. Opposite brain emotion-
regulation patterns in identity states of dissociative identity disorder: a PET
study and neurobiological model. Psychiatry Res. 2014;223(3):236–243.
Staniloiu A, Markowitsch HJ. Dissociative amnesia. Lancet Psychiatry.
2014;1(3):226–241. doi:10.1016/S2215-0366(14)70279-2.
CHAPTER 6
Mataix-Cols D, Rosario-Campos MC, Leckman JF. A multidimensional
model of obsessive-compulsive disorder. Am J Psychiatry. 2005;162:228–
238.
Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated
cortico-striatal pathways. Trends Cogn Sci. 2012;16(1):43–51.
CHAPTER 7
Davis H, Attia E. Pharmacotherapy of eating disorders. Curr Opin
Psychiatry. 2017;30(6):452–457.
Hutson PH, Balodis IM, Potenza MN. Binge-eating disorder: clinical and
therapeutic advances. Pharmacol Ther. 2018;182:15–27.
Smith AR, Zuromski KL, Dodd DR. Eating disorders and suicidality: what
we know, what we don’t know, and suggestions for future research. Curr
Opin Psychol. 2017;22:63–67.
CHAPTER 8
Adelson SL; American Academy of Child and Adolescent Psychiatry
(AACAP) Committee on Quality Issues (CQI). Practice parameter on gay,
lesbian, or bisexual sexual orientation, gender nonconformity, and gender
discordance in children and adolescents. J Am Acad Child Adolesc
Psychiatry. 2012;51(9):957–974.
Aitken M, Steensma TD, Blanchard R, et al. Evidence for an altered sex ratio
in clinic-referred adolescents with gender dysphoria. J Sex Med.
2015;12(3):756–763.
American Foundation for Suicide Prevention. Suicide Statistics. 2014.
https://afsp.org/about-suicide/suicide-statistics/.
Birmaher B, David B, Bernet W; AACAP Work Group on Quality Issues.
Practice parameter for the assessment and treatment of children and
adolescents with depressive disorders. J Am Acad Child Adolesc
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Bryant-Waugh R, Markham L, Kreipe RE, et al. Feeding and eating disorders
in childhood. Int J Eat Disord. 2010;43(2):98–111.
Center for Behavioral Health Statistics and Quality. The TEDS report: age of
substance use initiation among treatment admissions aged 18 to 30.
Rockville, MD: Substance Abuse and Mental Health Services
Administration.
https://www.samhsa.gov/data/sites/default/files/WebFiles_TEDS_SR142_AgeatInit_07
10-14/TEDS-SR142-AgeatInit-2014.htm.
Dulcan MK, ed. Dulcan’s Textbook of Child and Adolescent Psychiatry.
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urban disparities in youth suicides, United States, 1996-2010. JAMA
Pediatr. 2015;169(5):466–473.
Idring S, Rai D, Dal H, et al. Autism spectrum disorders in the Stockholm
Youth Cohort: design, prevalence and validity. PLoS One.
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Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-
onset distributions of DSM-IV disorders in the National Comorbidity
Survey Replication. Arch Gen Psychiatry. 2005;62(6):593–602.
March J, Susan S, Benedetto V. The treatment for adolescents with
depression study (TADS): methods and message at 12 weeks. J Am Acad
Child Adolesc Psychiatry. 2006;45(12):1393–1403.
Newschaffer CJ, Croen LA, Daniels J, et al. The epidemiology of autism
spectrum disorders. Annu Rev Public Health. 2007;28:235–258.
O’Brien KM, Vincent NK. Psychiatric comorbidity in anorexia and bulimia
nervosa: nature, prevalence, and causal relationships. Clin Psychol Rev.
2003;23(1):57–74.
Polanczyk GV, Willcutt EG, Salum GA, et al. ADHD prevalence estimates
across three decades: an updated systematic review and meta-regression
analysis. Int J Epidemiol. 2014;43(2):434–442.
Redcay E, Courchesne E. When is the brain enlarged in autism? A meta-
analysis of all brain size reports. Biol Psychiatry. 2005;58(1):1–9.
Shaw P, Lerch J, Greenstein D, et al. Longitudinal mapping of cortical
thickness and clinical outcome in children and adolescents with attention-
deficit/hyperactivity disorder. Arch Gen Psychiatry. 2006;63(5):540–549.
Smith HA, Fuchs DC, Pandharipande PP, et al. Delirium: an emerging
frontier in the management of critically ill children. Crit Care Clin.
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Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol. 2002;1(6):352–358.
Van der Kolk BA. Developmental trauma disorder. Psychiatric Ann.
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Wolraich M, Brown L, Brown RT; Subcommittee on Attention-
Deficit/Hyperactivity Disorder; Steering Committee on Quality
Improvement and Management; ADHD: clinical practice guideline for the
diagnosis, evaluation, and treatment of attention-deficit/hyperactivity
disorder in children and adolescents. Pediatrics. 2011;128(5):1007–1022.
CHAPTER 9
Kumar K, Kumar A, Keegan RM, et al. Recent advances in the neurobiology
and neuropharmacology of Alzheimer’s disease. Biomed Pharmacother.
2018;98:297–307.
Marcantonio ER. Delirium in hospitalized older adults. N Engl J Med.
2017;377(15):1456–1466.
van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive
impairment. Nat Rev Dis Primers. 2018;4:18004.
CHAPTER 10
Koob GF, Mason BJ. Existing and future drugs for the treatment of the dark
side of addiction. Annu Rev Pharmacol Toxicol. 2016;56:299–322.
Reus V, Fochtmann LJ, Bukstein O, et al. The American Psychiatric
Association Practice Guideline for the pharmacological treatment of
patients with alcohol use disorder. Am J Psychiatry. 2018;175(1):86–90.
Thomson AD, Cook CC, Touquet R, et al; Royal College of Physicians,
London. The Royal College of Physicians report on alcohol: guidelines for
managing Wernicke’s encephalopathy in the accident and emergency
department. Alcohol Alcohol. 2002;37:513–521.
Volkow ND, Morales M. The brain on drugs: from reward to addiction. Cell.
2015;162(4):712–725.
CHAPTER 11
Goodman M, New A, Siever L. Trauma, genes, and the neurobiology of
personality disorders. Ann N Y Acad Sci. 2004;1032:104–116.
Kool S, Schoevers R, de Maat S, et al. Efficacy of pharmacotherapy in
depressed patients with and without personality disorders: a systematic
review and meta-analysis. J Affect Disord. 2005;88:269–278.
Ruocco AC, Carcone DA. Neurobiological model of borderline personality
disorder: systematic and integrative review. Harv Rev Psychiatry.
2016;24(5):311–329.
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in Adults: A Systematic Review [Internet]. SBU Yellow Report No. 199.
Stockholm, Sweden: Swedish Council on Health Technology Assessment
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Tavel ME. Somatic symptom disorders without known physical causes: one
disease with many names? Am J Med. 2015;128(10):1054–1058.
CHAPTER 13
Marshall E, Claes L, Bouman WP, et al. Non-suicidal self-injury and
suicidality in trans people: a systematic review of the literature. Int Rev
Psychiatry. 2016;28(1):58–69.
van Heeringen K, Mann JJ. The neurobiology of suicide. Lancet Psychiatry.
2014;1(1):63–72.
CHAPTER 14
Kachigian C, Felthous AR. Court responses to Tarasoff statutes [review]. J
Am Acad Psychiatry Law. 2004;32:263–273.
Kim SY. Evidence-based ethics for neurology and psychiatry research
[review]. NeuroRx. 2004;1:372–377.
Moye J, Gurrera RJ, Karel MJ, et al. Empirical advances in the assessment of
the capacity to consent to medical treatment: clinical implications and
research needs. Clin Psychol Rev. 2006;26:1054–1077.
Palmer BW, Harmell AL. Assessment of healthcare decision-making
capacity. Arch Clin Neuropsychol. 2016;31(6):530–540.
CHAPTER 15
Lieberman JA, Stroup TS, McEvoy JP, et al; Clinical Antipsychotic Trials of
Intervention Effectiveness (CATIE) Investigators. Effectiveness of
antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med.
2005;353:1209–1223.
Stroup S, Lieberman JA, McEvoy JP, et al. Effectiveness of olzapine,
quetiapine, and risperiodone in patients with chronic schizophrenia after
discounting perphenazine: a CATIE study. Am J Psychiatry. 2007;164:3.
CHAPTER 16
Carreno FR, Frazer A. Vagal nerve stimulation for treatment-resistant
depression. Neurotherapeutics. 2017;14(3):716–727.
Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in
the treatment of mood disorders: a review and meta-analysis of the
evidence. Am J Psychiatry. 2005;162:656–662.
Philip NS, Nelson BG, Frohlich F, et al. Low-intensity transcranial current
stimulation in psychiatry. Am J Psychiatry. 2017;174(7):628–639.
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intravenous ketamine on suicidal ideation: a systematic review and
individual participant data meta-analysis. Am J Psychiatry.
2018;175(2):150–158.
CHAPTER 17
Cipriani A, Pretty H, Hawton K, et al. Lithium in the prevention of suicidal
behavior and all-cause mortality in patients with mood disorders: a
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1819.
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Neuro-Psychopharmacology (CINP) treatment guidelines for bipolar
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evidence, and a precise algorithm. Int J Neuropsychopharmacol.
2017;20(2):121–179.
Post RM. The new news about lithium: an underutilized treatment in the
United States. Neuropsychopharmacology. 2018;43(5):1174–1179.
CHAPTER 18
Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders.
Dialogues Clin Neurosci. 2017;19(2):93–107.
Williams T, Hattingh CJ, Kariuki CM, et al. Pharmacotherapy for social
anxiety disorder (SAnD). Cochrane Database Syst Rev. 2017;
(10):CD001206.
CHAPTER 19
Joseph A, Ayyagari R, Xie M, et al. Comparative efficacy and safety of
attention-deficit/hyperactivity disorder pharmacotherapies, including
guanfacine extended release: a mixed treatment comparison. Eur Child
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O’Brien JT, Holmes C, Jones M, et al. Clinical practice with anti-dementia
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for Psychopharmacology. J Psychopharmacol. 2017;31(2):147–168.
CHAPTER 20
Sachdev PS. Neuroleptic-induced movement disorders: an overview [review].
Psychiatr Clin North Am. 2005;28:255–274.
Wang RZ, Vashistha V, Kaur S, et al. Serotonin syndrome: preventing,
recognizing, and treating it. Cleve Clin J Med. 2016;83(11):810–817.
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de Mello MF, de Jesus Mari J, Bacaltchuk J, et al. A systematic review of
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GENERAL REFERENCES
American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders, 5th ed. Arlington, VA: American Psychiatric
Publishing, 2013.
Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock’s Synopsis of
Psychiatry: Behavioral Science/Clinical Psychiatry, 11th ed. Philadelphia,
PA: LWW, 2014.
Uptodate Clinical Reference
Charney DS, Sklar P, Buxbaum JD, et al. Neurobiology of Mental Illness, 4th
ed. New York, NY: Oxford University Press, 2013.
Stahl SM. Prescriber’s Guide: Stahl’s Essential Psychopharmacology, 6th
ed. Cambridge, UK: Cambridge University Press, 2017.
Note: Page numbers followed by t refer to tables; page numbers
followed by f refer to figures.
A
AA (Alcoholics Anonymous), 90, 95
Abuse
elder, 125
substance, 37, 42, 87, 106
Acamprosate, 93
for alcohol use disorder, 163t, 164–165
Acetylcholine, 75–76, 76f
Acetylcholinesterase inhibitors, 163t, 165–166
for Alzheimer’s disease, 78
Activities of daily living (ADLs), 61, 78
Acute psychotic syndromes, causes of, 5t
Acute stress disorder, 38
AD. See Alzheimer’s disease
Adderall, 164
ADHD. See Attention-deficit/hyperactivity disorder
Adjustment disorder, 38–39
clinical manifestations of, 39
epidemiology of, 38
etiology of, 39
management of, 39
ADLs (activities of daily living), 61, 78
Adolescent-focused treatment, for anorexia nervosa, 53
Adolescent psychiatric conditions, child and, 59t, 65–68
anxiety disorders, 65
bipolar disorders, 68
childhood feeding, and eating disorders
infancy, feeding disorder of, 66
pica, 65–66
rumination disorder, 66
depressive disorders, 67
disruptive, impulse control, and conduct disorders
conduct disorder, 66–67
oppositional defiant disorder, 67
elimination disorders, 66
gender dysphoria, 66
interviews and assessments with, 58–59, 60t
introduction to, 58
pediatric delirium, 68
posttraumatic stress disorder, 68
Affective flattening, with schizophrenia, 4t
Agoraphobia, 30–31
clinical manifestations of, 30–31
epidemiology of, 31
etiology of, 31
management of, 31
Agranulocytosis, with antipsychotics, 138
Akathisia, 168t, 169
Alanon, 90
Alcohol-induced persisting amnestic disorder, 93
Alcohol-related disorders
alcohol intoxication, 92
alcohol use disorder, 90–92
epidemiology of, 91
etiology of, 91
management of, 92
alcohol withdrawal, 92, 92t
neurocognitive disorders, 92–93
pharmacologic management of, 93
Alcohol use disorder
acamprosate for, 164–165
antisocial personality disorder and, 106
disulfiram for, 165
naltrexone for, 163t, 164
Alcoholics Anonymous (AA), 90, 95
Aldehyde dehydrogenase inhibitor, 163t
Alogia, with schizophrenia, 4t
α-receptor medications, 163t
clonidine, 162
guanfacine, 163
prazosin, 162–163
α-2 receptor agonist, 96
Alprazolam, 33, 158t
Alzheimer’s disease (AD), 79t, 80–81f, 162, 165–166
acetylcholinesterase inhibitors for, 78
caprylidene for, 163t, 166
tacrine for, 78
Amantadine, for extrapyramidal syndrome, 169
Amenorrhea, 53
Amphetamine, 96
intoxication, 96–97
withdrawal of, 97
Androgen insensitivity syndrome, 114
Anhedonia, 6
Anorexia nervosa
binge-eating/purging type, 53
bulimia nervosa v., 53
epidemiology of, 52–53
etiology of, 53
management of, 53–54
restricting type, 53
Anticholinergics, 162, 163t
for dystonia, 169
for extrapyramidal syndrome, 169
side effects of, 137
Anticonvulsants, for autism spectrum disorder, 62
Antidepressants, 109, 140–144, 141t
for bereaved individuals with depression, 126
indications for, 140, 141t
mechanisms of action, 140–142, 142f
selection of, 142–143
side effects of, 143–144
suicide attempts and, 124
therapeutic monitoring of, 143
Antipsychotics, 124, 133–138, 153
for acute mania, 14
adverse drug reactions of, 133t, 137–138
for agitation, 97
atypical, 134t, 136
choice of, 136–137
mechanism of action, 134–135, 135f
for personality disorders, 109
side effects of, 133t, 137–138
agranulocytosis, 138
anticholinergic, 137
cardiac, 138
hypotension, 138
metabolic effects, 138
movement disorders, 138
reduced seizure threshold, 137
therapeutic monitoring, 137
typical, 133t, 135, 135f
Antisocial personality disorder (ASP), 91, 106
Anxiety, defined, 28
Anxiety disorders, 28–34, 28t
agoraphobia, 30–31
generalized, 33–34
diagnostic criteria for, 33t
epidemiology of, 33
etiology of, 33
management of, 34
neural basis of, 28, 30f
panic disorder, 29–30, 29t
separation, 65
social, 65
social phobia, 32–33
epidemiology of, 32
etiology of, 32
management of, 33
specific phobia, 31–32
epidemiology of, 31
etiology of, 31
management of, 32
Anxiolytic-related disorders
clinical manifestations of, 94, 94t
epidemiology of, 94
Anxiolytics, 156–160
benzodiazepines, 156–159
mechanism of action, 156–157, 156–157f
selection of, 157–159, 158t
buspirone, 159–160
indications for, 159
mechanism of action, 159–160
Apnea, defined, 117
Aripiprazole, 14, 134t, 136, 137, 153
Armodafinil, for narcolepsy, 163t, 165
ASD. See Autism spectrum disorder
Asenapine, 134t, 136
ASP (antisocial personality disorder), 91, 106
Asperger’s syndrome, 62
Atomoxetine, 64, 163t, 164
Attention-deficit/hyperactivity disorder (ADHD), 62–64, 162
epidemiology of, 63
etiology of, 62–63
medications used for
atomoxetine, 164
guanfacine, 163
psychostimulants, 164
Atypical depressions, 24, 143
Atypical neuroleptics, 62
Autism spectrum disorder (ASD), 58, 61–62
epidemiology of, 62
etiology of, 61
management of, 62
Avoidant personality disorder, 108
Avolition, with schizophrenia, 4t
B
Barbiturates, 94
Behavioral theory, 176, 176t, 177, 177t
for attention-deficit/hyperactivity disorder, 63–64
Benzodiazepines, 80, 94, 165
for acute mania, 14
for alcohol withdrawal, 92
for anxiety, 109
for catatonia, 9
for delirium tremens, 92–93
and depersonalization/derealization disorder, 42
for generalized anxiety disorder, 34
mechanism of action, 156–157, 156–157f
for panic disorder, 30
selection of, 157–159, 158t
active metabolites, 159
elimination half-life, 159
metabolism, route of, 159
onset, rate of, 157, 159
potency, 157
Benztropine, 163t
Bereavement, 39, 125–126
β-blockers, 109, 152, 162, 163t
for akathisia, 169
for social phobia, 33
Binge-eating disorder, 53, 54–56
epidemiology of, 54
management of, 55
medical complications of, 55, 56t
prevention for, 56
Bipolar disorders, 13–16, 14t, 16f
bipolar I disorder, 13–15, 14t
epidemiology of, 13
bipolar II disorder, 15
in children and adolescents, 68
cyclothymic disorder, 15–16
epidemiology of, 15
etiology of, 15
management of, 16
due to another medical condition, 16
neural basis of, 13
substance-induced, 16
Bipolar I disorder, 13–15, 14t, 16f
defined, 14
epidemiology of, 13
management of, 14–15, 153
Bipolar II disorder, 15, 16f
Body dysmorphic disorder, 47–48
Borderline personality disorder, 107
Brexpiprazole, 134t
Brief psychotic disorder, 7
Bulimia nervosa, 54, 66
anorexia nervosa vs., 53
Buprenorphine, 96
for opiate use disorder, 163t, 164
Bupropion, 64, 144
for cocaine-related depression, 96
Buspirone, 94, 159–160
indications for, 159
mechanism of action, 159–160
C
CAGE mnemonic, 91, 91t
Cannabis, 97
Caprylidene, for Alzheimer’s disease, 163t, 166
Carbamazepine, 14–15, 153
choice of, 150t, 153
mechanism of action, 153
side effects of, 151t, 153
therapeutic monitoring of, 153
Cariprazine, 134t
Catatonia, 8–9
clinical manifestations of, 8–9, 9t
epidemiology of, 8
management of, 9
prognosis for, 9
risk factors for, 8
Catatonic specifier, 24
CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), 136–
137
CBT. See Cognitive-behavioral therapy
Central nervous system stimulant use disorders
withdrawal, 97
Central sleep apnea, 117–118
Childhood feeding, and eating disorders
infancy, feeding disorder of, 66
pica, 65–66
rumination disorder, 66
Chlordiazepoxide, 158t
Chlorpromazine, 133t, 136
Circadian rhythm sleep–wake disorders, 118
Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), 136–
137
Clomipramine, 49, 140
for obsessive-compulsive disorder, 47
Clonazepam, 158t
Clonidine, 64, 96, 162, 163t
Clozapine, 14, 124, 134t, 136, 137, 138
for tardive dyskinesia, 171
Club drugs, 97–98
γ-hydroxybutyrate, 98
3,4-methylenedioxymethamphetamine, 97–98
ketamine, 98
lysergic acid diethylamide, 98
methamphetamine, 98
rohypnol, 98
Cluster A (odd and eccentric) personality disorders, 105–106
paranoid personality disorder, 105–106
schizoid personality disorder, 106
schizotypal personality disorder, 106
Cluster B (dramatic and emotional) personality disorders, 106–108
antisocial personality disorder, 106
borderline personality disorder, 107
histrionic personality disorder, 107
narcissistic personality disorder, 107–108
Cluster C (anxious and fearful) personality disorders, 108–109
avoidant personality disorder, 108
dependent personality disorder, 108
obsessive-compulsive personality disorder, 108–109
Cocaine, 96
withdrawal of, 97
Cognitive-behavioral therapy (CBT), 177
for body dysmorphic disorder, 48
for decreasing cannabis use in teens, 97
for depersonalization/derealization disorder, 42
for major depressive disorder, 67
for panic disorder, 29–30
for separation anxiety disorder, 65
for trichotillomania, 49
Cognitive theory, 176, 176t
Communication disorders, 61
Compulsions, defined, 47
Conduct disorder, 66–67
Conversion disorder, 112
Crystal methamphetamine. See Methamphetamine
Cyclothymic disorder, 15–16, 16f
epidemiology of, 15
etiology of, 15
management of, 16
D
d-amphetamine, 64
dACC (dorsal anterior cingulate cortex), 46
DBT. See Dialectical-behavioral therapy
Debtors Anonymous, 90
Deep-brain stimulation, 145
Delirium, 75–77
epidemiology of, 76
etiology of, 75–76, 75t, 76f
management of, 77
neurocognitive disorder v., 77t
tremens, 92–93
Delusional disorder, 7–8, 8t
epidemiology of, 7
etiology of, 7
management of, 8
with schizophrenia, 4, 4t
Dementia
medications used for, 165–166, 166f
caprylidene, 166
memantine, 163t, 166
Dependent personality disorder, 108
Depersonalization/derealization disorder (DPD/DRD), 41–42
Depressive disorders, 19–24, 19t
categories of, 19
in children and adolescents
disruptive mood dysregulation disorder, 67
major, 67
disruptive mood dysregulation disorder, 22–23
etiology of, 23
management of, 23
due to another medical condition, 24
major, 19–22, 22f
epidemiology of, 21
etiology of, 21
persistent, 22, 22f
premenstrual dysphoric disorder, 23
substance/medication-induced, 23–24
subtypes of, 24
Desipramine, for cocaine-related depression, 96
Developmental theory, 174–176, 175t
Dextroamphetamine, 163t, 164
Dialectical-behavioral therapy (DBT), 109, 177–178
for depersonalization/derealization disorder, 42
Diazepam, 158t
Dicyclomine, for abdominal cramping, 96
DID. See Dissociative identity disorder
Diphenhydramine, 163t
Disruptive, impulse control, and conduct disorders
conduct disorder, 66–67
oppositional defiant disorder, 67
Disruptive mood dysregulation disorder (DMDD), 22–23
etiology of, 23
management of, 23
Dissociative amnesia, 41
Dissociative disorders, 36t, 39–42, 40t
depersonalization/derealization disorder, 41–42
dissociative amnesia, 41
dissociative identity disorder, 39–41
epidemiology of, 40
etiology of, 40
management of, 41
neural basis of, 40
Dissociative identity disorder (DID), 39–41
epidemiology of, 40
etiology of, 40
management of, 41
neural basis of, 40
Disulfiram, 93
for alcohol use disorder, 163t, 165
DMDD. See Disruptive mood dysregulation disorder
Donepezil, 163t, 165–166
Dopamine, 2, 2f
antagonists, 133t, 135–136, 135f
hypothesis, 2, 134
reuptake inhibitor, 163t
Dorsal anterior cingulate cortex (dACC), 46
Down syndrome, 59
DPD/DRD (depersonalization/derealization disorder), 41–42
Drive psychology, 174
Duloxetine, 144
Dysthymia. See Persistent depressive disorder
Dystonia, 168–169, 168t
E
Eating disorders, 52–56
anorexia nervosa, 52–54
etiology of, 53
binge-eating disorder, 54–56
epidemiology of, 54
management of, 55
medical complications of, 55, 56t
prevention for, 56
bulimia nervosa, 54
classification of, 52t
neural basis of, 52
ECT. See Electroconvulsive therapy
EEG (electroencephalogram), 58–59, 115
Ego psychology, 174, 175t
Elder abuse, 125
Electric shock therapy. See Electroconvulsive therapy
Electroconvulsive therapy (ECT), 22, 145
for bipolar disorder, 14
for catatonia, 9
for depression, 124
Electroencephalogram (EEG), 58–59, 115
Elimination disorders, 66
Encopresis, in children, 66
Enuresis, in children, 66
EPS (extrapyramidal syndrome), 168t, 169
Erikson’s life cycle stages, 175t
Escitalopram, 30
Eszopiclone, for insomnia, 163t, 165
Excoriation disorder, 49–50
epidemiology of, 49
etiology of, 49
management of, 50
Exposure therapy
for agoraphobia, 31
for specific phobia, 32
Extrapyramidal syndrome (EPS), 168t, 169
F
Factitious disorder, 112–113
Family-based treatment, for anorexia nervosa, 53
Family therapy, for personality disorders, 109
Flooding
Floppy baby syndrome, 159
Fluoxetine, 30, 136, 153
for bulimia nervosa, 54
Fluphenazine, 133t, 136
Flurazepam, 158t
Folate, for alcohol use disorder, 92
Fragile X syndrome, 59, 61
Frontotemporal dementia, 79t, 81f
Functional neurologic symptom disorder. See Conversion disorder
G
GABA-B
agonist, 163t
receptors, 165
GABA modulators, 163t
Gabapentin, 14, 33, 34
GAD. See Generalized anxiety disorder
Galantamine, 163t, 165–166
Gamblers Anonymous, 90
γ-aminobutyric acid (GABA), 1, 3, 76
receptor, 29, 94, 156–157, 156–157f, 165
γ-hydroxybutyrate (GHB), 98
Gender dysphoria, 114–115
Gender identity disorder. See Gender dysphoria
Gender-reassignment surgery, 114
Generalized anxiety disorder (GAD), 33–34
epidemiology of, 33
etiology of, 33
management of, 34
GHB. See γ-Hydroxybutyrate
GHB agonist, 163t
Glutamate, 2–3, 3f
modulator, 163t
Glutamatergic N-methyl-d-aspartate receptor, 144, 144f
Guanfacine, 64, 163, 163t
H
Hair-pulling disorder. See Trichotillomania
Hallucinations, with schizophrenia, 3, 4t
Haloperidol, 65, 133t, 136, 138
for delirium, 77
Histrionic personality disorder, 107
HIV. See Human immunodeficiency virus
Hoarding disorder, 48–49
epidemiology of, 48
etiology of, 48
management of, 49
Hormonal therapy, 114
HPA (hypothalamic–pituitary–adrenal) axis, 19, 123
Human immunodeficiency virus (HIV), 79t, 95
Huntington’s disease, 80t, 82f
Hypersomnolence disorder, 116
Hypertension, prazosin for, 162–163
Hypochondriasis. See Illness anxiety disorder
Hypomania, 15
Hypopnea, 117
Hypotension, with antipsychotics, 138
Hypothalamic–pituitary–adrenal (HPA) axis, 19, 123
Hypoventilation, sleep-related, 118
I
Illness anxiety disorder, 112
Iloperidone, 134t, 138
Infancy, feeding disorder of, 66
Informed consent, 129, 130f
Insomnia, 116
medications used for, 165
Intellectual development disorder. See Intellectual disability
Intellectual disability, 59–61
epidemiology of, 59
etiology of, 59
Intelligence quotient (IQ), 58, 64
Interpersonal psychotherapy, for major depressive disorder, 67
Interpersonal therapy (IPT), 177
Intimate partner violence, 125
Involuntary commitment, 129–130
IPT (interpersonal therapy), 177
IQ (intelligence quotient), 58, 64
K
Ketamine, 98, 144, 144f
Ketone producer, 163t
Korsakoff’s syndrome. See Alcohol-induced persisting amnestic disorder
L
Lamotrigine, 14, 152–153
for bipolar disorders, 68
choice of, 150t, 152–153
Language disorder, 61
Laryngeal dystonia. See Laryngospasm
Laryngospasm, 168–169
Legal issues, of medicine, 129–130
informed consent, 129, 130f
involuntary commitment, 129–130
malpractice, 129
mandatory reporting, 130
M’Naghten rule, 130
Tarasoff decisions, 130
Levothyroxine, 163t
Lewy body, 79t, 81f
Lithium, 14–15
mechanism of action, 149, 151
suicide attempts and, 124
therapeutic monitoring of, 151–152
Lorazepam, 158t
Loxapine, 133t
LSD (lysergic acid diethylamide), 98
Lurasidone, 134t, 136
for bipolar disorder, 153
Lysergic acid diethylamide (LSD), 98
M
Magnesium, for alcohol use disorder, 92
Major depressive disorder (MDD), 19–22, 22f
epidemiology of, 21
etiology of, 21
Major neurocognitive disorder, 77–80
clinical manifestations of, 77t, 78
epidemiology of, 78, 79–80t
etiology of, 75t, 78
management of, 78, 80
Malingering, 111, 112
Malpractice, 129
Manic episode, 13, 14, 14t
MAOIs. See Monoamine oxidase inhibitors
MDMA (3,4-methylenedioxymethamphetamine), 97–98
Melancholic depression, 24
Melatonin agonist, 163t, 165
Memantine, for dementia, 163t, 166
Mesoridazine, 138
Metabolic effects, of psychotropic agents, 171–172
Methadone, 96, 163t, 164
Methamphetamine, 96, 98
Methylphenidate, 64, 96, 163t, 164
Mirtazapine, 144
for akathisia, 169
M’Naghten rule, 130
Modafinil, for narcolepsy, 163t, 165
Molindone, 133t
Monoamine oxidase inhibitors (MAOIs), 171
side effects of, 143–144
Mood disturbance, schizoaffective disorder, 5
Mood stabilizer medication, 109, 124, 149–154, 149t. See also Specific
medications
for bipolar disorder, 14–15
indications for, 149, 150–151t, 150t
Movement disorders
with antipsychotics, 138
medication-induced, 168t
Multiple personality disorder. See Dissociative identity disorder
μ-opioid
antagonist, 93, 163t, 164
receptor, 96
Muscle dysmorphia, 47
N
N-acetylcysteine, for excoriation disorder, 50
N-methyl-d-aspartate (NMDA) receptor, 2–3, 3f, 96
antagonist, 163t, 164
Naloxone, 96, 164
Naltrexone, 93
for alcohol use disorder, 163t, 164
Narcissistic personality disorder, 107–108
Narcolepsy, 116–117
modafinil, 165
sodium oxybate, 165
Narcotics Anonymous, 90, 97
NCDs. See Neurocognitive disorders
Nefazodone, 144
Negative symptoms, of schizophrenia, 3–4, 4t
Neonatal withdrawal syndrome, 164
Neural basis
of anxiety disorders, 28, 30f
of bipolar disorders, 13
of depressive disorders, 19, 20f
of dissociative identity disorder, 40
of eating disorders, 52
of obsessive-compulsive disorder, 46
of personality disorders, 104–105, 105f
of posttraumatic stress disorder, 37, 38f
of psychotic disorders, 1
of substance use disorder, 88–90, 89f, 90f
of suicide attempts, 123
Neurocognitive disorders (NCDs), 75–82, 75t
delirium, 75–77
epidemiology of, 76
etiology of, 75–76, 75t, 76f
management of, 77
major, and mild, 77–80
clinical manifestations of, 77t, 78
epidemiology of, 78, 79–80t
etiology of, 75t, 78
management of, 78, 80
subtypes of, 79–80t, 80–82
epidemiology of, 82
etiology of, 80, 82
management of, 82
Neurodevelopmental disorders, 59–65, 59t
attention-deficit/hyperactivity disorder, 62–64
epidemiology of, 63
autism spectrum disorder, 61–62
epidemiology of, 62
etiology of, 61
management of, 62
communication disorders, 61
intellectual disability, 59–61
epidemiology of, 59
etiology of, 59
specific learning disorder, 64
Tourette’s disorder, 64–65
epidemiology of, 64
etiology of, 64
management of, 65
Neuroleptic-induced Parkinsonism. See Extrapyramidal syndrome
Neuroleptic malignant syndrome (NMS), 168t, 169–171, 170t
Neuroleptics
atypical, 62
high-potency, 65
Nicotinic partial agonist, 163t
Nightmare disorder, 118
NMS (neuroleptic malignant syndrome), 168t, 169–171, 170t
Nonbenzodiazepine hypnotics, 165
Non–rapid eye movement (NREM) sleep arousal disorders, 118
O
Object relations theory, 174
Obsessions, defined, 47
Obsessive-compulsive disorder, 46–47, 112, 140
epidemiology of, 46
management of, 47
neural basis of, 46
Obsessive-compulsive personality disorder, 108–109
Obstructive sleep apnea hypopnea, 117
OCD. See Obsessive-compulsive disorder
Ocular muscle dystonia, 169
ODD. See Oppositional defiant disorder
Olanzapine, 14–15, 134t, 136, 153
Opiate use disorder
buprenorphine for, 163t, 164
methadone for, 163t, 164
naltrexone for, 163t, 164
Opioid antagonist, 163t
Opioid use disorders
defined, 95
epidemiology of, 95
management of, 96
withdrawal, symptoms of, 95t
Oppositional defiant disorder (ODD), 63
in children, 67
Overeaters Anonymous, 90
Oxazepam, 158t
Oxcarbazepine, 153
P
Paliperidone, 134t, 136
Panic disorder, 29–30, 29t
epidemiology of, 29
etiology of, 29
Paranoid personality disorder, 105–106
Paraphilic disorders, 113–114, 114t
Parasomnias, 118
Parkinson’s disease (PD), 79t, 98
Partial μ-opioid agonist, 163t
PCP (phencyclidine), 2, 3f
PD (Parkinson’s disease), 79t, 98
Pediatric delirium, 68
Pemoline, 163t
Pentobarbital challenge test, 94–95
Peripartum depression, 24
Perphenazine, 133t
Persistent complex bereavement disorder, 125–126
Persistent depressive disorder, 22, 22f
Personality disorders, 104–109, 104t
antisocial, 106
avoidant, 108
borderline, 107
cluster A (odd and eccentric), 105–106
cluster B (dramatic and emotional), 106–108
cluster C (anxious and fearful), 108–109
dependent, 108
histrionic, 107
narcissistic, 107–108
neural basis of, 104–105, 105f
obsessive-compulsive, 108–109
paranoid, 105–106
primary ego defense mechanisms in, 104t
schizoid, 106
schizotypal, 106
Pharmacotherapy, 82
Pharyngeal dystonia, 169
Phencyclidine (PCP), 2, 3f
Phobias, 31–32, 31t
Phototherapy, 145
Pica, 65–66
Pimavanserin, 137
Pimozide, 65, 133t, 138
Polysomnography, 114–116f, 115–116, 115t
Positive symptoms, of schizophrenia, 3–4, 4t
Posttraumatic stress disorder (PTSD), 36–38, 37t
epidemiology of, 36
management of, 38
Posturing, and catatonia, 8–9
Pragmatic communication disorder. See Social communication disorder
Prazosin, 38, 162–163, 163t
Premenstrual dysphoric disorder, 23
Priapism, 144
Prion disease, 79t
Promethazine, for nausea, 96
Propranolol, 152, 163t
Pseudodementia, 78
Psychoanalytic/psychodynamic theory, 174
Psychodynamically based therapies, for personality disorders, 108–109
Psychoeducation, for bipolar disorders, 68
Psychological theories, 174–176
behavioral theory, 176, 176t, 177t
cognitive theory, 176, 176t
developmental theory, 174–176, 175t
psychoanalytic/psychodynamic theory, 174
twentieth-century psychodynamic schools, 174, 175t
Psychosis, 1
Psychosocial treatments, for schizophrenia, 4–5
Psychostimulants, 163t, 164
for binge-eating disorder, 55
Psychotherapy, 15
behavioral therapy, 177
for binge-eating disorder, 55
cognitive-behavioral therapy, 177
for delusional disorder, 8
for depression, 21
dialectical-behavioral therapy, 177–178
interpersonal therapy, 177
for personality disorders, 108–109
for posttraumatic stress disorder, 38
short-term psychodynamic, 176–177
Psychotic disorders, 1–9, 2t
brief psychotic disorder, 7
catatonia, 8–9
causes of, 5t
delusional disorder, 7–8, 8t
neural basis for, 1
schizoaffective disorder, 5–6
schizophrenia, 1–5, 2t
schizophreniform disorder, 6–7
Psychotic features, 1
Psychotic specifier, 24
PTSD. See Posttraumatic stress disorder
Purging disorder, 53, 54
Q
Quetiapine, 14–15, 134t, 136, 138, 153
Quinine, for muscle aches, 96
R
Ramelteon, for insomnia, 163t, 165
Rapid eye movement (REM) sleep disorder, 21, 118
Refeeding syndrome, 55
Relaxation techniques, for generalized anxiety disorder, 34
REM (rapid eye movement) sleep disorder, 21, 118
Repetitive transcranial magnetic stimulation (rTMS), 145
Restless legs syndrome, 118
Restricting type disorder, 53
Risk management, defined, 129
Risperidone, 15, 134t, 136, 138, 153
Rivastigmine, 163t, 165–166
Rohypnol, 98
rTMS (repetitive transcranial magnetic stimulation), 145
Rumination disorder, 66
S
Schizoaffective disorder, 5–6
epidemiology of, 5
etiology of, 6
risk factors for, 5
Schizoid personality disorder, 106
Schizophrenia, 1–5, 4t
diagnostic evaluation for, 4
differential diagnosis of, 4, 5t
history and mental status examination, 3–4, 4t
epidemiology of, 1
etiology of, 2–3
γ-Aminobutyric acid, 3
dopamine, 2, 2f
glutamate, 2–3, 3f
risk factors for, 1
subtypes of, 3
Schizophreniform disorder, 6–7
epidemiology of, 6
etiology of, 6
management of, 7
risk factors for, 6
Schizotypal personality disorder, 106
Seasonal depressive disorders, 24
Sedative-hypnotic use disorder, 94–95
epidemiology of, 94
withdrawal, signs and symptoms of, 94t
Seizure threshold, with antipsychotics, 137
Selective norepinephrine reuptake inhibitors, 163t, 164
Selective serotonin reuptake inhibitors (SSRIs)
for body dysmorphic disorder, 48
for posttraumatic stress disorder, 38
for social anxiety disorder, 65
for trichotillomania, 49
Separation anxiety disorders, 65
Serotonin antagonists, 136, 136f
Serotonin reuptake inhibitor, 169
antidepressants, 94
Serotonin syndrome, 170t, 171, 171t
Sertraline, 30
Sex Anonymous, 90
Sexual dysfunction, 113, 113t
Short-course schizophrenia, 6
Short-term psychodynamic psychotherapy, 176–177
Skin-picking disorder. See Excoriation disorder
Sleep architecture, normal, 115–116, 115–116f, 115t
Sleep disorders
breathing-related
central sleep apnea, 117–118
obstructive sleep apnea hypopnea, 117
sleep-related hypoventilation, 118
hypersomnolence, 116
insomnia, 116
narcolepsy, 116–117
non–rapid eye movement, 118
rapid eye movement, 118
substance/medication-induced, 118
Sleep-related hypoventilation, 118
Sleep stages, 115, 115f, 115t, 116f
Sleep–wake cycle, 76
Sleep–wake disorders, 115–118, 117t
breathing-related sleep disorders, 117–118
circadian rhythm sleep–wake disorders, 118
normal sleep architecture, 115–116, 115t, 115–116f
parasomnias, 118
polysomnography, 114–116f, 115–116, 115t
sleep disorders, 116–117
substance/medication-induced sleep disorder, 118
Smoking cessation, varenicline for, 163t, 165
Social anxiety disorders, 65. See also Social phobia
Social communication disorder, 61
Social phobia, 32–33
epidemiology of, 32
etiology of, 32
management of, 33
Sodium oxybate, for narcolepsy, 163t, 165
Somatic symptom, and related disorders, 111–113, 111t
conversion disorder, 112
factitious disorder, 112–113
illness anxiety disorder, 112
somatic symptom disorder, 112
Somatic symptom disorder, 106, 112
Somatic therapies, 145
Special K. See Ketamine
Specific learning disorder, 64
Specific phobia, 31–32
epidemiology of, 31
etiology of, 31
management of, 32
Specific substance use disorders
acamprosate, 164–165
buprenorphine, 164
disulfiram, 165
naltrexone, 164
varenicline, 165
Speech disorders, 61
SSRIs. See Selective serotonin reuptake inhibitors
Stanford-Binet Intelligence Scale, 58, 60
Stevens-Johnson’s syndrome, 153
Substance use disorder, 87–88, 87t
alcohol
intoxication, 92
neurocognitive disorders, 92–93
pharmacologic management, 93
use, 90–92
withdrawal, 92, 92t
amphetamines, 96
withdrawal of, 97
cannabis, 97
club drugs, 97–98
γ-hydroxybutyrate, 98
3,4-methylenedioxymethamphetamine, 97–98
ketamine, 98
lysergic acid diethylamide, 98
methamphetamine, 98
rohypnol, 98
cocaine, 96
withdrawal of, 97
defined, 88
impaired control, domain of, 87–88, 87t
neural basis of, 88–90, 89f, 90f
opioids, 95–96
pharmacologic domain, 87t, 88
rehabilitation, and recovery, 90
risky use, domain of, 87t, 88
sedative, hypnotic, and anxiolytic drugs, 94–95, 94t
social impairment, domain of, 87t, 88
Substance/medication induced disease, 79t
Substance/medication-induced sleep disorder, 118
Suicide attempts
epidemiology of, 123
neural basis of, 123
risk factors for, 123–124
with schizophrenia, 4
Suprachiasmatic nucleus, 116, 117f
Systematic desensitization
T
Tacrine, for Alzheimer’s disease, 78
TADS (Treatment of Adolescents with Depression Study), 67
Tarasoff decisions, 130
Tardive dyskinesia (TD), 168t, 171
TBI (traumatic brain injury), 79t
TCAs. See Tricyclic antidepressants
TD (tardive dyskinesia), 168t, 171
Temazepam, 158t
Thiamine, for alcohol use disorder, 92
Thioridazine, 133t, 138
Thiothixene, 133t
Third wave therapies, 178
3,4-Methylenedioxymethamphetamine (MDMA), 97–98
Thyroid hormone, 166
receptor agonists, 163t
Tourette’s disorder, 64–65
epidemiology of, 64
etiology of, 64
management of, 65
Transcranial magnetic stimulation, 22
Transient psychosis, 97
Trauma- and stressor-related disorders, 36–39, 36t
acute stress disorder, 38
adjustment disorder, 38–39
epidemiology of, 38
etiology of, 39
management of, 39
posttraumatic stress disorder, 36–38, 37t
epidemiology of, 36
management of, 38
Trauma-focused therapy, for dissociative identity disorder, 41
Traumatic brain injury (TBI), 79t
Trazodone, 80, 144
for akathisia, 169
for insomnia, 165
Treatment of Adolescents with Depression Study (TADS), 67
Triazolam, 158t
Trichotillomania, 49
Tricyclic antidepressants (TCAs)
Trifluoperazine, 133t
Trihexyphenidyl, 163t
Tryptophan hydroxylase gene, 123
Twentieth-century psychodynamic schools, 174, 175t
U
Unipolar mood disorders, 21, 22f, 143, 151
V
Vagal nerve stimulation, 22
Vagus nerve stimulation (VNS) therapy, 145
Valproate, 14–15, 152
Valproic acid, for bipolar disorders, 68
Varenicline, for smoking cessation, 163t, 165
Vascular disease, 79t
Venlafaxine, 144
Vilazodone, 144
Vitamin supplementation, for alcohol use disorder, 92
VNS (vagus nerve stimulation) therapy, 145
Vortioxetine, 144
W
Wechsler Intelligence Scale for Children–Revised (WISC-R), 58, 60
Wernicke-Korsakoff’s syndrome, 93
Wernicke’s encephalopathy, 92, 93
WISC-R (Wechsler Intelligence Scale for Children–Revised), 58, 60
of amphetamines, 97
from barbiturates, 94
from cannabis, 97
of cocaine, 97
from delirium, 94
from opioids, 95, 95t
from sedative-hypnotic drugs, 94
Z
Zaleplon, for insomnia, 163t, 165
Ziprasidone, 15, 134t, 136, 138, 153
Zolpidem, for insomnia, 163t, 165

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Acquisitions Editor: Matt Hauber

Development Editor: Andrea Vosburgh

Copyright © 2019 by Wolters Kluwer

Copyright © 2009 by Lippincott Williams & Wilkins, a Wolters Kluwer

Library of Congress Cataloging-in-Publication Data

ISBN-13: 978-1-4963-8134-7 | eISBN: 9781496381392

Cataloging-in-Publication data available on request from the Publisher.

This work is no substitute for individual patient assessment based upon

Given continuous, rapid advances in medical science and health information,

5 Trauma and Stressor-Related Disorders and

6 Obsessive-Compulsive and Related Disorders

8 Neurodevelopmental Disorders and Child and

13 Special Clinical Topics

16 Antidepressants and Somatic Therapies

20 Major Adverse Drug Reactions

21 Psychological Theory and Psychotherapy

Ramzi Mardam Bey, MD

Ronald L. Cowan, MD, PhD

Sonia Matwin, PhD

Michael J. Murphy, MD, MPH

Adam Pendleton, MD, MBA

Yasas Chandra Tanguturi, MBChB

Jose Arriola Vigo, MD

TABLE 1-1. Psychotic Disorders

It is important to understand that primary psychotic disorders

FIGURE 1-1. Dopamine: For dopamine receptor type 2 (D2)

History and Mental Status Examination

Affective Decreased expression of emotion, such as lack of

To make the diagnosis (Table 1-3), two (or more) of the

TABLE 1-3. 1-Diagnostic Criteria for Schizophrenia

Patients with schizophrenia generally have a history of

TABLE 1-4. Causes of Acute Psychotic Syndromes

History and Mental Status Examination

History and Mental Status Examination

BRIEF PSYCHOTIC DISORDER

History and Mental Status Examination

History and Mental Status Examination

TABLE 1-5. Delusional Disorder Subtypes

TABLE 1-6. Symptoms of Catatonia

History and Mental Status Examination

1. What diagnosis is least likely on the differential diagnosis list?

2. Which of the following criteria are NOT used to make a diagnosis

3. If the patient has a positive urine drug screen for

1. The most likely diagnosis is:

2. The least likely diagnosis on the differential diagnosis is:

3. The prognosis with treatment is:

TABLE 2-1. Bipolar Disorders

TABLE 2-2. Bipolar I Disorder

Children can present with bipolar disorder that resembles the

History and Mental Status Examination

History and Mental Status Examination

BIPOLAR DISORDER DUE TO ANOTHER

3. The next most reasonable step would be to:

1. What is the most likely diagnosis at the time of this visit?

2. What is the most likely useful regimen?

TABLE 3-1. Depressive Disorders

MAJOR DEPRESSIVE DISORDER

Mood changes consist of depressed mood most of the day,

History and Mental Status Examination

FIGURE 3-2. Unipolar mood disorders. (A) Major depressive disorder.