Insomnia

Victoria E Judd M.D.

 Sleep Quotes
• People who say they • O sleep, O gentle sleep,
sleep like a baby usually Nature's soft nurse, how
don't have one. ~Leo J. have I frighted thee,
Burke That thou no more wilt
• If people were meant to weigh my eyelids down
pop out of bed, we'd all And steep my sense in
sleep in toasters. Author forgetfulness?
unknown ~William Shakespeare,
Henry IV, Part I
 Insomnia
• No disclosures
 Objectives
• Learn about sleep
• List pathogenesis/types of insomnia
• Discuss epidemiology of insomnia
• Learn about the impact of insomnia
• List common etiologies of insomnia
• Discuss therapy
-Cognitive-behavioral therapy
-Pharmacologic treatment
 Sleep Is
• Active
• Complex
• Highly Regulated
• Involves different areas in the brain
• Purpose is not understood
• Essential to life/necessary
• We all do it
 Sleep Deprivation
• Our 24/7 lifestyle can be deleterious

• Trying to push through the night and stifle a

yawn, yet that yawn is the first sign that you’re
not so awake as you might like to think – after
18 hours in the absence of sleep, your
reaction time slows from ¼ of a second to ½ of
a second, and then becomes still longer
 Sleep Deprivation
• One starts experiencing several bouts of
‘micro-sleep’ – and so, while driving you zone
out for say 20 seconds and drift out of your
lane, or if studying late then you find yourself
rereading the same passage – thus your
reaction time becomes roughly equivalent to a
person with a blood alcohol level of 0.08,
sufficient to get you arrested in 49 states
 Sleep Deprivation
• Charles Augustus Lindbergh, in 1927, in his
Spirit of St. Louis, during his 1st solo Atlantic
crossing from Long Island to Paris,
experienced visual hallucinations which
remitted with recovery sleep
• There is a 10% increase in MVA’s following
switching to daylight savings when the day is
shortened by 1 hour
 Consequences of Insomnia
30.00%
% Reporting sleep disorder

25.00%
20.00%
Sleep apnea
15.00%
Insomnia
10.00%
5.00%
0.00%
1 or 2
0 (n=8337) > 3 (n=130)
(n=2297)
Sleep apnea 7.10% 6.70% 19.20%
Insomnia 16.70% 18% 26.10%
Number of accidents
 Sleep Deprivation
• Mood disturbance with irritability, transient
paranoia, disorientation, performance deficits,
severe fatigue or hypomania – all sequelae of
prolonged sleep deprivation
• Chronic sleep deprivation may reach a point at
which the very ability to catch up on sleep is
damaged, such that what’s lost is lost
• Bodes ill for students, soldiers, et. al, trying to
acquire new information while sleep-deprived
 Sleep Disorders
• Sleep disorders are common
• Sleep disorders are serious
• Sleep disorders are treatable
• Sleep disorders are underdiagnosed
 Sleep
• Sleep Stages
• Stage 1- transition to sleep, 5% of total time
• Stage 2- 50% of total time
• Stage 3 & 4- Most restorative sleep , slow
wave sleep, 20-24% of total sleep time
• Rapid eye movement (REM)- 20-25% of total
sleep time (When we dream)
 Sleep
• Normal sleep starts with stage 1-2-3-4-3-2-
REM
• The cycle repeats at 10-120 (90) minute
intervals
• There are 3 to 4 cycles a night
• Stage 3 & 4 are more prominent in the first
half of the night and decrease as time goes on
• REM is less prominent in the first half of the
night and increases as time goes by
Sleep Cycle
 Sleep
• Sleep varies with age
• Infants sleep 66% of the day
• Young adults sleep 33% of the day
• Older adults sleep less, wake more, have less
stage 3, 4 and REM sleep
• More REM sleep better learning in students
• The last 2 hours of REM sleep tend to be the most
important for integrating new information
 The Need For Sleep
• Over the years, the need for REM sleep
decreases considerably, while the need for
NREM sleep diminishes less sharply
 Insomnia - DSM IV criteria
1. Difficulty initiating or maintaining sleep, or
non-restorative sleep, for at least 1 month.
2. Clinically significant distress or impairment in
social/occupational functioning
3. Not exclusively due to another sleep disorder
4. Not exclusively due to another mental
disorder
5. Not due to the physiological effects of a
substance or a medical disorder
 Insomnia
Insomnia is present when all three of the
following criteria are met:
• A complaint of difficulty initiating sleep, difficulty
maintaining sleep, or waking up too early.
• The above sleep difficulty occurs despite
adequate opportunity and circumstances for
sleep.
• The impaired sleep produces deficits in daytime
function.
 Features of Insomnia
• Problems initiating sleep (greater than 30 minutes)
• Frequent and/or prolonged nocturnal awakenings
• Early morning awakenings with an inability to return
to sleep
• Poor sleep quality and sleep efficiency
• Cognitive arousal typically reported

• Severity is judged along several dimensions, including

frequency, intensity and duration of sleep difficulties.
Also impact on daytime functioning, mood and quality
of life.
 Insomnia-Hyperarousal
• In experimental models of insomnia, healthy subjects
deprived of sleep do not demonstrate the same
abnormalities in metabolism, daytime sleepiness, and
personality as subjects with insomnia. In an experimental
model in which healthy subjects were given caffeine,
causing a state of hyperarousal, the healthy subjects had
changes in metabolism, daytime sleepiness, and personality
similar to the subjects with insomnia.
• These results support a theory that insomnia is a
manifestation of hyperarousal. In other words, the poor
sleep itself may not be the cause of the daytime
dysfunction, but merely the nocturnal manifestation of a
general disorder of hyperarousability.
 Impact of Insomnia
• Biological

• Poor function of immune system

• Functional impairments

• Increased risk of accidents

• More likely to report lack of concentration and
motivation
• Reduced productivity, work/school absenteeism
• Increased use of health care services
 Impact of Insomnia
• Psychological health

• Increases risk of developing depression,

anxiety or substance dependence
• Risk factor in suicide
– (Ohayon et al., 1997: Harvey, 2001: Ancoli-
Israel & Roth, 1999: McCrae & Lichstein,
2001)
 Impact of Insomnia
• Knutson et al found that the quantity and quality
of sleep correlate with future blood pressure. In
an ancillary to the Coronary Artery Risk
Development in Young Adults (CARDIA) cohort
study, measurement of sleep for 3 consecutive
days in 578 subjects showed that shorter sleep
duration and lower sleep maintenance predicted
both significantly higher blood pressure levels
and adverse changes in blood pressure over the
next 5 years.
 Types of Insomnia, Time
• Transient insomnia: episodic
– Acute illness
– Jet lag
– Shift change
• Short-term insomnia: few days to 3 weeks
– Major life event
– Substance abuse
• Chronic insomnia : longer than 4 weeks
– Chronic illness
– Psychiatric illness
 Circadian Related Insomnia, Time
• Time zone change (jet lag) syndrome
• Shift work sleep disorder
• Irregular sleep-wake pattern
• Delayed sleep phase syndrome
• Advanced sleep phase syndrome
• Non-24-hour sleep-wake disorder
• Circadian rhythm sleep disorder
• Shifts with age (adolescent or elderly)
 Chronic Insomnia
• Complaint of poor sleep causing distress or
impairment for 1 to 6 months or longer
• Average less than 6.5 hours sleep per day
• Or 3 episodes per week of:
– Taking longer than 30 minutes to fall asleep
– Waking up during the night for at least an hour
• Not accounted for by another sleep disorder, mental
illness, medical illness or substance abuse.
 Types of Insomnia
Primary insomnia
• Idiopathic insomnia — Insomnia arising in infancy or
childhood with a persistent, unremitting course
• Psychophysiologic insomnia — Insomnia due to a
maladaptive conditioned response in which the patient
learns to associate the bed environment with heightened
arousal rather than sleep; onset often associated with an
event causing acute insomnia, with the sleep disturbance
persisting despite resolution of the precipitating factor
• Paradoxical insomnia (sleep-state misperception) —
Insomnia characterized by a marked mismatch between the
patient’s description of sleep duration and objective
polysomnographic findings
 Types of Insomnia
Secondary insomnia
• Adjustment insomnia — Insomnia associated with active
psychosocial stressors
• Inadequate sleep hygiene — Insomnia associated with
lifestyle habits that impair sleep
• Insomnia due to a psychiatric disorder — Insomnia due to
an active psychiatric disorder, such as anxiety or depression
• Insomnia due to a medical condition — Insomnia due to a
condition such as the restless legs syndrome, chronic pain,
nocturnal cough or dyspnea, or hot flashes
• Insomnia due to a drug or substance — Insomnia due to
consumption or discontinuation of medication, drugs of
abuse, alcohol, or caffeine
 Proper Diagnosis
• The medical interview is everything
• Focus on underlying causes
• Sleep partner should be present for the
interview if possible
• Full medication list is required (OTC, Rx,
Natural)
• Substances and alcohol use
 Interview
• Sleep history…is there trouble with:
- falling asleep?
- maintaining sleep?
- not being able to go back to sleep?
- early awakenings?
- not feeling rested?
- daytime consequences?
 Interview
• Daytime consequences can you function/stay
awake to drive?
• Do you experience (or bed-partner report): Leg or
arm jerking while asleep? (periodic limb
movement disorder)
• Loud snoring/gasping/choking, or stopping
breathing when asleep? (sleep apnea)
• Uncomfortable feelings in your legs that go away
with moving them? (restless leg syndrome)
 Interview
• Patients with insomnia typically feel fatigued
during the day, but are unable to fall asleep if
given a chance to lie down to take a nap.
• Patients with poor nocturnal sleep due to
other sleep disorders readily fall asleep during
the day. ( Except poor sleep hygiene.)
 Interview
• Usual bedtime
• Usual morning awakening time
• Time spent in bed awake prior to sleeping,
and following the onset of sleep
• Estimated time spent asleep
• Do you take anything to make you sleep?
• Do you drink to help you go to sleep?
• What else do you do in your bedroom?
 Interview
Anything disruptive to sleep?
• Computer
• Noises
• Lights
• Snoring partner/roommate
• Partner/roommate with different bed/wake times
• TV
• Pets
• Not feeling safe where you sleep
 Interview
• Do you consume: nicotine, caffeine, alcohol,
other stimulants, decongestants prior to
bedtime?
• Half lives are important!
• Do you smoke/eat when you wake up, or perform
other tasks like cleaning?
• Do you check the clock when you wake up early?
• What is your pre-bedtime routine: exercise, work,
TV, eating?
 Interview-Stimulants
Some Common Sources:

• Coffee: a cup of Joe with ~100-150 mg of

caffeine = 1 mg of amphetamine
• Red Bull: 250 mL = 80 mg of caffeine
• Baker’s Chocolate: 1 oz = 26 mg of caffeine
• Tea: variable
 Interview
• Medical issues
• Medication changes
• Lifestyle issues
• Work stress
• School stress
• Financial stress
• Relationship stress
• Complaints from partner
 Stressful Life Events
• Loss of a loved one
• Divorce/Separation
• Loss of employment
• Arguments
• Particularly happy or sad events
• Work demands
• School demands
• Injuries
• Illnesses
 Medical Conditions Associated With
Insomnia
• Hyperthyroidism
• Arthritis or any other chronic painful condition
• Chronic lung or kidney disease
• Cardiovascular disease (heart failure, CAD)
• Heartburn (GERD)
• Neurological disorders (epilepsy, Alzheimer’s,
headaches, stroke, tumors, Parkinson’s Disease)
• Diabetes
• Menopause/Menstrual disorders
 Some Medications that Cause
Insomnia
• Alcohol • Corticosteroids
• Caffeine/chocolate • Decongestants
• Nicotine/nicotine patch • Antidepressants
• Beta blockers • Thyroid hormones
• Calcium channel • Anticonvulsants
blockers • High blood pressure
• Bronchodilators medications
 Psychiatric Causes of Insomnia
• Depression • Adjustment disorders
• Generalized Anxiety • Personality disorders
Disorder • Bipolar disorder
• Stress • Dysthymia
• Post Traumatic Stress • Anxiety
Disorder • Psychosis including
• Obsessive Compulsive schizophrenia
Disorder
 Types of Insomnia
• Comorbid insomnia
– Sleep disturbance is comorbid with an underlying
problem
 Causes of Insomnia
4%
6%
6%
Psychiatric
36% Psychophysiologic
9% Drug-alcohol
RLS/PLMD
Misperception
Sleep apnea
12% Medication
Others

12% 15%
 Epidemiology
• More than half of adults in the U.S. said they
experienced insomnia at least a few nights a
week during the past year
• Nearly one-third said they had insomnia
nearly every night
• Increases with age
• The most frequent health complaint after pain
• Twice as common in women as in men
 Epidemiology
• 69 % have insomnia-occasional 50 % and
chronic 19 %
• 35 percent insomnia during the previous year
(50% serious)
• Approximately 10 % of individuals develop
chronic insomnia with related daytime
consequences
 Insomnia
Variables associated with the onset of
insomnia include:
• a previous episode of insomnia
• a family history of insomnia
• a predisposition toward being more easily
aroused from sleep
• poorer self-rated health
• more body pain
 CONTRIBUTING FACTORS TO
DEVELOPMENT OF INSOMNIA
• Predisposing factors • Perpetuating factors
– Personality – Conditioning
– Sleep-wake cycle – Substance abuse
– Circadian rhythm – Performance anxiety
– Coping mechanisms – Poor sleep hygiene
– Age
• Precipitating factors
– Situational
– Environmental
– Medical
– Psychiatric
– Medications
 Most Common Daytime Complaints
• Fatigue or malaise
• Poor attention or concentration
• Social, school, or vocational dysfunction
• Mood disturbance-More sadness, depression, and
anxiety
• Daytime sleepiness
• Cognitive impairment
• School or work days missed
 Most Common Daytime Complaints
• Reduced motivation or energy
• Increased errors or accidents
• Tension, headache, or gastrointestinal
symptoms
• Ongoing worry about sleep
• Risk taking behavior
• Deficits in academic performance
• Poorer Health
 Consequences of Insomnia
• The National Sleep Foundation found that
students who reported insufficient sleep
performed worse on tests had lower grades.
Those who reported getting enough sleep had
A’s and B’s.
• Thus students who are chronically sleepy may
chose easier courses in college. Thus limiting
their future options.
 Consequences of Insomnia
• Even though students may compensate by
getting extra sleep on the weekend, this is not
enough to compensate for the lost sleep
during the week, resulting in a mounting sleep
deficit.
 Consequences of Insomnia
• Worsens psychiatric disorders
• Prolongs medical illnesses
• Reduced quality of life
• Higher health care costs
 Depression and Insomnia
• Insomnia is both a risk factor for depression
and a consequence of depression
• Could effective management of insomnia
decrease the incidence of depression?
• Could effective management of insomnia
modify the risk for relapsing depression?
 Insomnia Assessment
• Interview
• Physical exam
• Labs: TSH & Free T4, Glucose and Hgb A1C,
BUN & Cr, Iron Studies
• Psychometric
– Anxiety & Depression Questionnaires
– Sleep Disorders Questionnaire
 Measures of Sleep
• Insomnia Severity Index
• Epworth Sleepiness Scale (not good for
insomnia)
• Sleep Diaries
• Reports of partner
 How to keep track of your sleep
• Daily sleep diary or sleep log
– Bedtime
– Falling asleep time
– Nighttime awakenings
– Time to get back to sleep
– Waking up time
– Getting out of bed time
– Naps
 Non-drug treatments
• Cognitive-behavioral therapy (CBTI)
– Stimulus control
– Cognitive therapy
– Sleep restriction
– Relaxation training
– Sleep hygiene
– Cognitive therapy
 Insomnia - CBTI model (Espie,91)
Alertness/ Arousal

CNS Activity Psychological Enviromental

Direct Indirect Emotional Cognitive Situational Temporal

sleep region in brain autonomic arousal e.g. anxiety, stress e.g. planning, worry TV, work, exercise, food association of bed & sleep
 CBTI
• Stimulus control
• Sleep hygiene
• Sleep restriction
• Relaxation
• Paradoxical intention
• Cognitive restructuring
• Worry postponement
 Insomnia
Stimulus Control

• Insomnia is a conditioned response to temporal and

environmental cues

• Promote consistent sleep / wake cycle

• Re-associate the bedroom with sleeping

• Well established stand alone treatment

 BEHAVIORAL TREATMENTS
• Stimulus control therapy
– Assumes that there is a learned associated between
wakefulness and the bedroom
– To break the cycle, the patient must not spend time wide
awake in the bedroom
– Go to bed only when sleepy
– Do not use the bedroom for sleep-incompatible activities
– Leave the bedroom if awake for more than 20 minutes
– Return to bed only when sleepy
– Repeat if necessary
– Do not nap during the day
– Arise at the same time every morning
 Insomnia

Sleep Hygiene Education

• Factors that affect sleep, e.g. caffeine, alcohol, etc.

• Not primary cause of insomnia but can maintain problem
• Limited benefits if used alone, Not sufficient as a stand alone
treatment
•Specific behaviors will directly interfere with the ability to sleep
•The behaviors can be changed with education
 Sleep Hygiene
• Having good sleep hygiene knowledge is
weakly associated with good sleep hygiene
but is not related to overall sleep quality.
• Practicing good sleep hygiene is strongly
related to good sleep quality.
 Sleep Hygiene
 Fix a bedtime and an awakening time
 Avoid napping during the day
 Avoid alcohol, nicotine, chocolate before bed
 Avoid caffeine containing beverages 4 – 6 hours before
bedtime
 Avoid heavy, spicy, acidic or sugary foods before bed
 Regular exercise is good, not before bedtime
 Comfortable bedding
 Bedroom cool, dark, quiet
 Bedroom reserved for sleep and sex – NOT a work
room
 Sleep Hygiene
• Avoid trying to sleep
– You can’t make yourself sleep, but you can set the stage for
sleep to occur naturally
• Avoid a visible bedroom clock with a lighted dial
– Don’t let yourself repeatedly check the time!
– Turn the clock around or put it under the bed
 More healthy sleep habits
• Expose yourself to bright light at the right time
– Morning, if you have trouble falling asleep at night
– Night, if you want to stay awake longer at night
• Establish a regular sleep schedule
– Get up at the same time 7 days a week
– Go to bed at the same time each night
• Exercise every day - exercise improves sleep!
• Deal with your worries before bedtime
– Plan for the next day before bedtime
– Set a worry time earlier in the evening
– Keep a journal
 More healthy sleep habits
• Adjust the bedroom environment
– Sleep is better in a cool room, around 65 F.
– Darker is better
– If you get up during the night to use the bathroom, use
minimum light
– Use a white noise machine, a fan, or ear plugs to drown
out other sounds
– Make sure your bed and pillow are comfortable
– If you have a partner who snores, kicks, etc., you may have
to move to another bed (try white noise first) (try ear
plugs)
– Change resident hall quiet hours
 Healthy Sleep Habits
• Boring activities: reading the phone book,
count, etc.
• TV/video games do not count as relaxing or
boring—the flashing lights stimulate the brain.
 Insomnia

Sleep Restriction

• Reducing time in bed to match sleep obtained

• To increase sleep efficiency
• Adherence is problematic
• Probably efficacious treatment
 Sleep Restriction - best if done with a
professional
• Cut bedtime to the actual amount of time you
spend asleep (not in bed), but no less than 4
hours per night
• No additional sleep is allowed outside these
hours
• Record on your daily sleep log the actual
amount of sleep obtained
 Sleep Restriction (cont’d)
• Compute sleep efficiency (total time asleep
divided by total time in bed)
• Based on average of 5 nights’ sleep efficiency,
increase sleep time by 15 minutes if efficiency
is >85-90%
• With elderly, increase sleep time if efficiency
>80% and allow 30 minute nap.
 Sleep Restriction
• If sleep efficiency falls to less than 80%,
decrease time in bed by 15 minutes
• Have set, daytime hours (whenever possible).
• As sleep consolidation improves, time in bed
(and asleep) increases.
• Creates a mild state of sleep deprivation, and
thus promotes more rapid sleep onset and
more efficient sleep
 Insomnia

Relaxation

• To deactivate arousal system

• Various types - muscular, imaging, hypnosis, etc.
• Well established treatment
 BEHAVIORAL TREATMENTS
Plan a relaxation period before bed, develop a
bedtime routine.
Relaxation Therapy:
• Progressive muscle relaxation* best
• EMG Biofeedback* best
• Meditation
• Imagery training
• Self-hypnosis
• Diaphragmatic breathing
 Relaxation training
• More effective than no treatment, but not as
effective as sleep restriction
• More useful with younger compared with older
adults
• Engage in any activities that you find relaxing shortly
before bed or while in bed
– Can include listening to a relaxation tape, soothing music,
muscle relaxation exercises, a pleasant image
 Insomnia

Paradoxical Intention

• Engage in the feared outcome (not sleeping)

• Break cycle of performance anxiety
• Large variance in response
 Paradoxical Intention Treatment
• Paradoxical intention treatment is based on the
concept that performance anxiety helps prevent
proper sleep.
• The treatment involves persuading the individual with
insomnia to engage in the most feared behavior, which
to that individual is "staying awake."
• As the patient stops trying to fall asleep, the
performance anxiety of trying to fall asleep slowly
disappears.
• Studies show this approach is more effective than
control groups.
 Insomnia
Cognitive Restructuring

• Identify thought processes to reduce anxiety

• Includes self-talk, distraction, rationalization
• Helpful in altering dysfunctional sleep beliefs
• Postponing worry episodes
• Limited benefits if used alone, Not sufficient as a stand
alone treatment
 Cognitive Restructuring
• Identify beliefs about sleep that are incorrect
• Challenge their truthfulness
• Substitute realistic thoughts
 False beliefs about insomnia
• Misconceptions about causes of insomnia
– “Insomnia is a normal part of aging.”
• Unrealistic expectations re: sleep needs
– “I must have 8 hours of sleep each night.”
• Faulty beliefs about insomnia consequences
– “Insomnia can make me sick or cause a mental
breakdown.”
• Misattributions of daytime impairments
– “I’ve had a bad day because of my insomnia.”
– I can’t have a normal day after a sleepless night.”
More common myths about insomnia
• Misconceptions about control and
predictability of sleep
– “I can’t predict when I’ll sleep well or badly.”
• Myths about what behaviors lead to good
sleep
– “When I have trouble getting to sleep, I should
stay in bed and try harder.”
EFFICACY OF CBTI FOR INSOMNIA
EFFICACY OF CBT FOR INSOMNIA
 Benefits of CBTI
Benefits are long-lasting, even after therapy is
over
Relatively free of medical risks
No significant interactions with other medical
treatments
 The Down Side of CBTI
Monetary cost (repeated visits to a provider)
Improvement may not occur for several weeks
Requires time and motivation
Daytime sleepiness during sleep restriction
Lack of access to a trained therapist
Lack of therapist expertise
 Combined Treatment
CBTI can be used along with medications.

For example, medications can provide rapid

relief and CBTI can lead to long-lasting results.
The use of medication prior to the initiation of
behavioral therapy appears to be less
effective.
 Treatment of Insomnia
Pharmacologic:
• Sleeping Pills-Prescription
• Over the Counter
Pharmacologic Treatment of Insomnia
• Historic trials • Current
– Fermented beverages – Antihistamines
– Plant preparations – Benzodiazepine
– Laudanum hypnotics
(opium/alcohol) – Nonbenzodiazepine
– Chloral hydrate (Mickey hypnotics
Finn) – Selective melatonin
– Barbiturates receptor agonist
– Investigational
compounds
 MOST COMMONLY USED DRUGS FOR
INSOMNIA
1. Trazodone 9. Hydroxyzine
2. Zolpidem 10. Alprazolam
3. Amitriptyline 11. Lorazepam
4. Mirtazapine 12. Olanzapine
5. Temazepam 13. Flurazepam
6. Quetiapine 14. Doxepin
7. Zaleplon 15. Cyclobenzaprine
8. Clonazepam 16. Diphenhydramine
 Treatment of Insomnia
If you have to use drugs:
(Pharmacotherapy Guidelines):
• Use the lowest therapeutic dose
• Use for the shortest duration necessary
• Discontinue medication gradually
• Be alert for rebound insomnia
• Use agents with short half-lives to minimize
daytime sedation
• Best if started with CBTI
 Sleeping Pills
• Most common treatment approach
– Drowsiness common the next day
• NOT meant for chronic insomnia
– Effective for short-term (a couple weeks) insomnia only
• Tolerance and dependency may develop
• Withdrawal, rebound, relapse may occur
• But commonly used, despite the above
– 5-10% of adults have used a benzodiazepine in past year as
a sleep aid
– 10-20% of those over age 65 use sleeping pills
 Drug Treatment
Benzodiazepines-Approved by FDA
Non-benzodiazepine hypnotics-Approved by
FDA
Melatonin receptor agonists-Approved by FDA
Antidepressants
Antipsychotics
Antihistamines
 Benzodiapines
Many end in “pam” or “lam”
clonazepam (Klonopin)
lorazepam (Ativan)
diazepam (Valium)
alprazolam (Xanax)
temazepam (Restoril)
triazolam (Halcion)
 BZRA HYPNOTICS IN THE US

DRUG BRAND HALF-LIFE DOSE (mg)

(hrs)
Estazolam ProSom 8-24 1,2
Flurazepam Dalmane* 48-120 15,30
Quazepam Doral 48-120 7.5,15
Temazepam Restoril* 8-20 7.5,15,22.5,30
Triazolam Halcion 2-4 0.125,0.25
 BZRA PRESCRIBING GUIDELINES
• Bedtime dosing
• Avoid hazardous activities after dose
• Allow sufficient time in bed
• Dose adjustments
– Elderly and debilitated patients
– Hepatic impairment
• Nightly vs. as needed dosing
• Middle of the night dosing?
• Taper dose on discontinuation?
• Do not use in pregnant patients
 Benefits of Benzodiazepines
Enhance sleep

Decrease anxiety

Muscle relaxant
 BZRA DISCONTINUATION EFFECTS
• Rebound insomnia: sleep worsened relative to
baseline for 1-2 days
• Recrudescence: return of original insomnia
symptoms
• Withdrawal: new cluster of symptoms not
present prior to treatment
 BZRA ADVERSE EFFECTS
• Residual effects
• Dizziness
• Headache
• Blurred vision
• Nausea/diarrhea
• Fatigue
• Anterograde amnesia
• Sonambulism/complex sleep behavior
 Side Effects of Benzodiazepines
Daytime sedation
Decreased reaction time
Unsteadiness of gait—can lead to falls, ataxia
Cognitive impairment & memory problems
Risk of tolerance
Risk of withdrawal (and rebound insomnia)
Risk of abuse (do not use them in patients
with a history of substance abuse)
 Non-BZRA HYPNOTICS IN THE US

DRUG BRAND HALF-LIFE DOSE (mg)

(hrs)
Zolpidem Ambien 1.5-2.4 5,10
Zolpidem Ambien 2.8-2.9 6.25,12.5
ER CR
Zaleplon Sonata 1 5,10
Eszopiclone Lunesta 5-7 1,2,3
 Benefits of Non-benzodiazepines
Hypnotics
Bind to sub-types of GABA receptors that
specifically modulate sleep and therefore are
thought to have less unwanted side effects
Tolerance and abuse have not been shown to
be a major problem in the general population
In general have shorter duration of action
than most benzodiazepines and therefore are
less likely to cause next day sedation
 Side Effects of Non-benzodiazepines
Hypnotics
• Drowsiness
• Dizziness
• Unsteadiness of gait
• Rebound insomnia
• Memory impairment
 FDA Indications
Sleep onset only: zolpidem (Ambien) and
zaleplon (Sonata)
Sleep onset and sleep maintenance: zolpidem
ER (Ambien ER) and eszopiclone (Lunesta)
Eszopiclone (Lunesta) does not have a FDA
restriction on duration of usage
 FDA Indications
• Benzodiazepine receptor agonists
– Benzodiazepine hypnotics
• Temazepam (Restoril) (generic available)
• Flurazepam (Dalmane) (generic available)
– Nonbenzodiazepine hypnotics
• Zolpidem (Ambien) (generic available)
• Zaleplon (Sonata) (generic available)
• Eszopiclone (Lunesta) ( no generic available)

• Selective melatonin receptor agonist

– Ramelteon (Rozerem) (no generic available)
 Ramelteon
 Brand name is Rozerem
 Selective agonist at MT1 and MT2 melatonin receptors
 FDA approved for sleep-onset insomnia
 Only medication FDA approved for insomnia that is not
a controlled substance because it does not seem to
lead to abuse or withdrawal
 Associated with headache, dizziness, drowsiness,
fatigue and nausea
 Avoid with hepatic impairment and in pregnant women
 Ramelteon
• FDA approved for sleep onset insomnia
• No limitation on duration of use
• Non-sedating
• Single dose: 8 mg
• Take about 30 minutes prior to bedtime
• Half-life: 1-2.6 hrs
• No generic yet
 First Generation Antihistamine
• Postsynaptic histaminic and muscarinic
blockade
• Diphenhydramine
• Regulated by the FDA
• Half-life: 8 hrs
• Rapid tolerance to sedating effects
• Pill strengths (mg): 25, 37.5, 50
 First Generation Antihistamine
• Potential adverse effects
– Residual effects
– Delirium
– Dry mouth
– Constipation
– Blurred vision
– Urinary retention
– Narrow angle glaucoma exacerbation
– Paradoxical reaction
 Anti-depressants
Commonly used for insomnia but are not FDA
approved
Trazodone
Doxepin (Sinequan)
Amitriptyline
Mirtazapine (Remeron)
 Trazadone
Used at much lower doses for insomnia than
depression
The most commonly prescribed agent for
treating insomnia across all classes of
medications
No good research to support its use
Major side effects: sedation, dizziness, dry
mouth, orthostatic hypotension, priapism
(rare)
 The Tricyclic Antidepressants
amitriptyline (Elavil)
doxepin (Sinequan)

Side effects: dry mouth, urinary retention,

dizziness, daytime sedation, suppression of
REM sleep, QT prolongation
Used at much lower doses for insomnia than
depression
 Mirtazapine
Brand name: Remeron
Associated with weight gain, increased
appetite, daytime sedation and dizziness
 Antipsychotics
 Called the “atypical antipsychotics”
 Block dopamine from binding to receptors in the
brain
 Only use is for treating comorbid insomnia in
patients with primary indication for their use
 Examples:
 risperidone (Risperdal)
 olanzapine (Zyprexa)
 quetiapine (Seroquel)
 ziprasidone (Geodon)
 Anticonvulsants
• Low doses have some sedating and sleep
promoting effects
• The data is sparse
 Dietary Supplements
Not FDA regulated
• Valerian
• Kava-Kava
• Melatonin
• Passion flower
• Skullcap
• Lavender
• Hops
 Dietary/Herbal Sleep Preparations
(pea-shooters in the armamentarium)
Mostly: L-Tryptophan, Valerian, & Kava-kava

• L-Tryptophan: precursor of Serotonin, a

substrate for Melatonin – in milk (doesn’t
need to be warmed) & turkey – FDA has
limited availability after > 1,500 cases of
Eosinophilia Myalgia Syndrome with at least
37 deaths in 1989
 Dietary/Herbal (continued)
• Valerian (derivative of Valeriana officinalis plant):
mechanism may be via inhibiting GABA reuptake or
inhibiting postsynaptic potentials through activation
of adenosine receptors in cortical neurons – in one
study, little difference vs. Benadryl* - inhibitor of
CYP3A4 – withdrawal when extensive use, similar to
that seen with BZD’s – risk of hepatotoxicity &
delirium

* Sleep, 2005, 28: 1465-1471

 Dietary/Herbal (continued)
• Kava-kava: from root of Piper methysticum
plant endogenous to Western Pacific, and
used as hypnotic & anxiolytic – banned in
many countries due to reports of serious
hepatoxicity
______________________

• Others: Melatonin (OTC), Chamomilla (Sleepy-

Time Tea), & Passiflora
 Do Not Mix Medications
• Heath Ledger had insomnia
and passed away from an
accidental overdose of the
following medications:
• oxycodone
• hydrocodone
• diazepam
• temazepam
• alprazolam
• doxylamine
 Other Treatments of Insomnia
• Acupuncture
 Cultural Issues of Insomnia
• How long to sleep at night
• How long to nap
• Is insomnia to due too much work, physical
ailments, etc.
• Is insomnia a disease, a complaint, a disorder,
a symptom, a finding
 Brief Behavioral Treatment Plan for
Insomnia
Initial Visit
• (1) Screen positive for possible insomnia.
• (2) Assign sleep log and teach how to complete it
on daily basis for 2 weeks.
• (3) Teach how to calculate a daily sleep efficiency
score.
• Sleep efficiency is calculated by taking the ratio of
actual time spent asleep to time spent in bed
(expressed as a percentage, with higher numbers
indicating better sleep efficiency).
 Brief Behavioral Treatment Plan for
Insomnia
First Treatment Session (2 weeks later)
• (1) Review of sleep log, including sleep efficiency score,
especially to see the amount of time napping.
• (2) Discussion of bedtime habits (e.g., television watching,
reading, worrying, etc.).
• (3) Brief sleep education consisting of individual differences
in sleep needs, the effects of aging on sleep, and the
influence of sleep drive and circadian rhythms on sleep.
• (4) Teach stimulus control techniques including: (a)
eliminating nonsleep-related activities from bed and
bedroom, (b) following a consistent sleep-wake schedule,
and (c) avoiding daytime napping.
 Brief Behavioral Treatment Plan for
Insomnia
Second Treatment Session (4 weeks after
initial visit)
• (1) Review of first treatment session
instructions.
• (2) Problem-solving of any potential treatment
adherence problems.
• (3) Possible modification of patient's sleep
strategy and instructions to encourage future
independent trouble-shooting.
 Brief Behavioral Treatment Plan for
Insomnia
• Edinger and Sampson conducted a randomized trial of
primary care patients with insomnia.
• Their abbreviated behavioral therapy of two 25-minute
sessions was compared with a control group receiving
2 sessions of standard sleep hygiene instructions.
• Those in the treatment group had greater
improvements in their sleep efficiency and reductions
in their time awake after sleep onset than the control
group.
• This treatment can be successfully done by
nonmental health professionals, providers, working in
primary care settings.
 Take Home Points
• In practice parameters for nonpharmacologic treatments for
chronic insomnia, the American Academy of Sleep Medicine
recommends stimulus control as the approach with the best
scientific evidence for effectiveness.
• Progressive muscle relaxation, paradoxical intention, and
biofeedback are 3 treatments that have the next best scientific
evidence for effectiveness, while sleep restriction and
multicomponent cognitive behavioral therapy are recommended as
options.
• Focusing on sleep hygiene and single component cognitive therapy
may also be effective, but these approaches do not currently have
sufficient scientific evidence to recommend them as evidence-
based treatment. This is due to the insufficient number of clinical
trials studying the effectiveness of these treatments alone, without
their being part of any combined treatment regimen.
 Take Home Points
• In the immediate short term (i.e., first week),
medications can produce improvement at a
much greater rate than nonmedication
treatments.
• In the intermediate term (i.e., 3-8 weeks), a
meta-analysis indicates that behavioral
treatment for insomnia is just as effective as
medication treatment.
 Take Home Points
• There is the possibility that this effectiveness of
behavioral treatment is because it is more intensive
than medication treatment in that there is a greater
duration of contact with the healthcare professional.
• Over the long term (i.e., 6-24 months), patients
receiving nonpharmacologic therapies enjoy long
lasting relief while many of those treated with
medication return to their baseline insomnia levels.
• In summary, behavioral therapy is best for chronic
insomnia and helpful for all types.
 Take Home Points
Insomnia is defined by having daytime
symptoms.
There are two pathways for treating insomnia:
medications and CBTI. They can be used at
the same time.
All treatments have their pluses and their
minuses. Provider’s look at the patient’s
impairment and weigh that against the risk of
treatment.
 Take Home Points
• Patients with insomnia typically feel fatigued
during the day, but are unable to fall asleep if
given a chance to lie down to take a nap.
• Patients with poor nocturnal sleep due to
other sleep disorders readily fall asleep during
the day.
 Take Home Points
Many of the most common drugs for insomnia
are not FDA approved for that purpose.
No drug for insomnia is completely safe or
free of the risk of side effects.
Be sure that your patients informs you of all
medications they are taking, including over-
the-counter and herbal ones.
 Take Home Points
• Multidimensional Cognitive Behavioral
Therapy works better than both placebo and
pharmacotherapy (medicines) in short and
long term cases
• Interventions for sleep practices may need to
be culture specific
 Recommendations
• Acknowledge that students sleep habits are
significant concerns
• Educational programs have been shown to be
more effective the pharmacologic and CBTI
long term
• Examine course schedules, offer sections later
in the day
• Examine how campus and community
environments contribute to sleep difficulties
 Recommendations
• Do activities, schedules, sports, work routines
contribute to sleep difficulties
• Review life style issues; sleep, etc at all clinic
visits