Major Depression: Corina Freitas MS, MD, MBA, DABFM

MAJOR
DEPRESSION
Corina Freitas MS, MD, MBA, DABFM
DSM-5
Depressed mood or a loss of interest or pleasure in daily activities for more than two weeks.
Impaired function: social, occupational, educational.
Specific symptoms, at least 5 of these 9, present nearly every day:
Depressed mood or irritable most of the day, nearly every day, as indicated by either subjective
report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).
Decreased interest or pleasure in most activities

Significant weight change (5%) or change in appetite
Change in sleep: Insomnia or hypersomnia
Change in activity: Psychomotor agitation or retardation
Fatigue or loss of energy
Guilt/worthlessness: Feelings of worthlessness or excessive or inappropriate guilt
Concentration: diminished ability to think or concentrate, or more indecisive
Suicidality
MAJOR
DEPRESSION
SINGLE OR
RECURRENT
EPISODE
Figure 6-2 Stahls Essential

Pharmacology
IS MAJOR
DEPRESSIVE
DISORDER
PROGRESSIVE?
Figure 6-23 Stahls Essential

Psychopharmacology
PATHOPHYSIOLOGY
Norepinephrine
regulates itself via alpha2
locus coeruleus
Dopamine
regulates itself via D2
ventral tegmental area
Serotonin
regulates itself via 5HT1A, 5HT1B/D, 5HT3 and 5HT7
raphe nuclei
MIXED REGULATORS
Serotonin -> DA release 5HT1A, , DA inhibition 5HT2A w/ GABA and Glu
Serotonin -> DA and NE inhibition via 5HT2C
Serotonin -> DA + NE release via 5HT3
NE PRODUCTION AND
TERMINATION
NE RECEPTORS
1 5HT release
2 - autoreceptors (inhibition)
1 - cardiac
2 - lungs
3 lipolysis in adipose and
thermogenesis in skeletal muscle
HYPOTHESIS
Monoamine
Monoamine receptor
Lack of monoamines results in

1960s and 1970s
Depression due to lack of a
monoamine transmitters
Still lacking evidence
upregulation of post-synaptic
receptors
???
Lacking evidence
5HT2 low in suicide patient
10
TREATMENT
APA GUIDELINES
2010
11
PHARMACOTHERAPY
SSRIs = prevent reuptake of serotonin
SNRIs = prevent reuptake of serotonin and norepinephrine.
TCAs = prevent reuptake of norepinephrine and serotonin; block alpha-
adrenergic receptors and muscarinic receptors; have antihistaminic effect,

lower seizure threshold
MAOIs = may be good for atypical depression, issue w/ tyramine - except
Selegiline at low dose (MAO-B only) - many drug interactions especially

TCAs
Other
o Trazodone = Serotonin antagonist and reuptake inhibitor (SARI), most tested AE
-> Priapism
o Bupropion = norepinephrine-dopamine reuptake inhibitor (NDRI) lowers seizure
threshold; NO weight gain or sexual dysfunction
12
OTHER MODALITIES
To try during pregnancy and/or breastfeeding
o S-adenosyl methionine (SAMe) or St. Johns wort
o Bright light
ECT
o highest rates of response and remission
o 70%90% improvement.
o 2-3 times per week for 6-12 treatments or clear plateau
Psychotherapy
o CBT, Interpersonal, Problem-Solving and Psychodynamic
Deep Brain Stimulation subgenu of anterior cingulate cortex, part of the
ventromedial prefrontal cortex

TMS daily, 1hr+, several weeks
Vagus nerve stimulation (VNS) if no response to at least 4 adequate trials of treatment
(incl. ECT)
13
CHOOSING THERAPY
Effectiveness similar: SSRI, SNRI, TCA, MAOI and other. So what to do?
o Patient preference
o Prior response to medication
o Safety, tolerability, and anticipated side effects
o Co-occurring psychiatric or general medical conditions
o Pharmacological properties of the medication (e.g., half- life, actions on
cytochrome P450 enzymes, other drug interactions; etc)

o Cost
Usually optimal: SSRI, SNRI, mirtazapine, or bupropion; TCAs and MAOIs
2nd line
If no response at all in 1 month modify
If some response but more needed and at max -> augment
14
AUGMENTATION
APA
Another non-MAOI from different class
Lithium
2nd generation antipsychotic: Abilify
Thyroid Hormones= may boost monoamine neurotransmitters as downstream consequences of
thyroids known abilities to regulate neuronal organization, arborization, and synapse formation,
Triiodothyronine
Less Proof
l-5-Methyltetrahydrofolate (l-methylfolate): monoaminemodulator via BH4 factor
S-adenosyl-methionine (SAMe): needed for synthesis of monoamines
waste issue = homocysteine
Anticonvulsant
Omege 3
Stimulant
15
DID IT
WORK?
Response min 50%
16
RELAPSE
AND
RECURRENC
E
Not curable
Remissions or residual
symptoms
>20% recurrentce after 1st try
67% remission after 4th

treatment
Best response 25-64 yo
17
DOSING
18
SSRI SIDE EFFECT ISSUES

Headaches possibly bruxism or non-related
ED - Add sildenafil, tadalafil, buspirone, or bupropion.
Activation give in the am
Akathisia add BB or benzo
Bruxism ENT consult
Diaphoresis add terazosin (1 antagonist), clonidine (2 agonist) or
Cogentin (anticholinergic)
Falls BP monitor
Insomnia CBT, melatonin, sleep hygiene, morning dose
Nausea, Vomiting administer after or with food
Osteopenia Ca+D, monitor
Weight gain exercise, calorie restriction
19
SNRIS AES
similar to those of SSRIs but also include noradrenergic symptoms such as
sweating and dizziness.
20
TCA AES
alpha-adrenergic receptors: orthostatic hypotension, dizziness, or falls)
muscarinic receptors: anticholinergic effects, such as dry mouth, blurred
vision, constipation, and urinary retention
sedation (antihistamine effect)

lower the seizure threshold.
Dangerous in overdose => cardiac arrhythmias, may respond to
bicarbonate.
21
MAOIS AES
Do not give MAO inhibitors at the same time as SSRIs or meperidine =>
DEATH
If taken with tyramine-containing foods (especially wine and cheese) =>
hypertensive crisis.
22

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MAJOR

Decreased interest or pleasure in most activities

Figure 6-2 Stahls Essential

Figure 6-23 Stahls Essential

thermogenesis in skeletal muscle

Lack of monoamines results in

adrenergic receptors and muscarinic receptors; have antihistaminic effect,

MAOIs = may be good for atypical depression, issue w/ tyramine - except

Selegiline at low dose (MAO-B only) - many drug interactions especially

Deep Brain Stimulation subgenu of anterior cingulate cortex, part of the

ventromedial prefrontal cortex

cytochrome P450 enzymes, other drug interactions; etc)

Response min 50%

>20% recurrentce after 1st try

67% remission after 4th

Best response 25-64 yo

SSRI SIDE EFFECT ISSUES

sweating and dizziness.

vision, constipation, and urinary retention

sedation (antihistamine effect)

If taken with tyramine-containing foods (especially wine and cheese) =>

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