MAJOR DEPRESSIVE DISORDER (MDD)

Dr. Parna Haghparast

MasterClass 2024

NT involved in depression

 NT thought to be involved in depression:

o Serotonin (5-HT)
o Glutamate
o Acetylcholine (ACh)
o Dopamine (DA)
o Norepinephrine (NE)
o Epinephrine (Epi)

MDD Diagnostic Criteria

1. = or > 5 symptoms present during the same 2-week period (daily or nearly daily) and represent
a change in functioning
2. Symptoms:

M: Mood

S: Sleep increased/decreased

I: Interest/pleasure diminished

G: Guilt

E: Energy decreased

C: Concentration decreased

A: Appetite increased/decreased

P: Psychomotor agitation/retardation

S: Suicidal Ideation

3. Rule out bipolar disorder before starting antidepressants

Key drugs that can worsen depression: propranolol, atomoxetine, stimulants, Hormonal
contraceptives, Efavirenz, rilpivirine, steroids, Chantix, interferons, isotretinoin, methyldopa,
clonidine)
Treatment Resistant Depression:

 Patient should receive 4-8 week trial of medication at therapeutic dose before
concluding the drug is not working. If medication is not working, you can
o Change the antidepressant
o Increase dose
o Add an adjunct medication
 Buspirone
 Low-dose AP
 aripirazole,
 cariprazine,
 quetiapine XR,
 olanzapine/fluoxetine,
 brexpiprazole
 Spravato (Esketamine) nasal spray
 Lithium

Pharmacological Therapy:

1st line:

 SSRIs
 SNRIs
 Bupropion
 Mirtazapine

BBW: All antidepressant have boxed warning for increased suicidality in young adolescent

 Medication guide is required with all antidepressants

SSRIs: CI to be used with MOAI due to risk of Serotonin Syndrome

 Sertraline preferred in pt with Cardiac risk

 Paroxetine CI in pregnancy
 Most activating: Fluoxetine take in AM
 Most sedating: Paroxetine, fluvoxamine Take PM
 ADR: QTc prolongation (Citalopram, escitalopram), SIADH, N/V, sexual side effects,
tremor, dizziness, HA, somnolence/insomnia, increased risk of bleeding with NSAIDs
and anticoagulants
 Fluoxetine (Sarafem ®) Premenstrual Dyspori Syndrome (PMDD)
 Paroxetine (Brisdell ®) for vasomotor sx of menopause
 Two-weeks washout period with MOAIs (5-weeks for fluoxetine)
 STRONG CYP2D6 Inhibitors: Fluoxetine, Paroxetine
o Decreases effectiveness of Tamoxifen Venlafaxine preferred
SSRI combined mechanism: less sexual side effects

o Vilazodone (Viibryd): Take with food

o Vortioxetine (Trintellix)

SNRIs

 Similar ADR to SSRIs

 Watch out for high blood pressure in NAPLEX cases. Don’t pick SNRI is BP is high.
 Cymbalat: Also have FDA approval for fibromyalgia, diabetic neuropathies, GAD

TCAs: Blocks Ach and histamine receptors

 Secondar amines ae more selective for NE less side effects

o Nortryptylline (Pamelor)
 Tertiary amines may be slightly more effective but more side effects (more anticholinergic ADR)
o Eg. Amitryptylline (Elavil)
o Eg. Doxepin (Silenor brand name for insomnia)
 ADR: anticholinergic ADR, lowering of seizure threshold, QTc prolongation, weight gain,
overdose (arrhythmia), orthostasis

Miscellaneous

 Mirtazapine (Remeron): 15-45mg

o ADR: weight gain, sedation
 Bupropion (Wellbutrin, Zyban):
o CI: eating disorder, seizure
o Disturb sleeping, take in morning
o Insomnia, tremor/seizure, restlessness (dose-related)
o Sexual dysfunction is rare
 Trazodone
o Rare side effect: Priapism
o Commonly used for insomnia
 Nefazodone:
o BBW: for hepatotoxicity
o Rarely used in practice
 Post-partum depression:
o Brexanolone (Zulresso ®)
 IV infusion (weight-based) over 60 hours (2.5 days)
o Zuranolone (Zurzuvae ®):
 50 mg PO QD in the evening with fat-containing food for 14 days, alone
or as an adjunct to oral antidepressant therapy;
 BBW: Advise patients not to drive or engage in other potentially
hazardous activities until at least 12 hours after zuranolone
administration for the duration of the 14-day treatment course.
MOAI: Last line tx (eg. Selegiline patch, trancyclopramine, phenelzine, isocarboxazid

o Do not pick MOAI as first line on NAPLEX

o Highly serotonergic
 MAOI + SSRI/SNRI/TCA: serotonin syndrome
 Avoid use within 14 days other serotonergic agents (Fluoxetine needs 5
week washout period)
 MOA: increase NE, 5-HT and DA through inhibition monoamine enzyme
 Types
o Non-selective (MAOI-A + MAOI-B): phenelzine, isocarboxazid,
Tranylcypromine
o Selective MAOI (MAOI-B): Selegiline PATCH
 Side Effects: postural hypotension, hypertensive crisis and serotonin syndrome with
Tyramine containing food (eg. Aged, smoked cheese, wine, pickled food, fermented
foods ef. Saukraut, soy sauce)
 Sympathomimetic drugs hypertension crisis (HTN, hyperthermia, mental status
change)
o Pseudoephedrine, phenylephrine, dextromethorphan
o Stimulants e.g amphetamines

WATCH OUT:

 Do NOT combine two SSRI, SSRI + SNRI

 Antidepressants need to be tapered off due to risk of discontinuation syndrome (EXCEPT
fluoxetine due to long half life)
 Antidepressants take 6-8 weeks for full effect
 Watch out for serotonin syndrome with serotinergic medications (ex. Linezolid
(Zyvoxx), Meperidine, MOAI, St. John wort, 5Ht3 antagonists such as ondansetron,
Triptans, methylene blue, tramadol, lithium)
 Mild-moderate psychotherapy first
 Eliminate drugs that are NOT first line (AP, mood stabilizers, fluvoxamine, MOAI,
TCAs)
 1st line: SSRIs/SNRIs/Wellbutrin/Mirtazapine/Vortioxetine (if left with two options on
NAPLEX, look for CI, side effects that would rule out one of the medications)
 Sertraline preferred in cardiac disease
 Wellbutrin CI in. seizures, recent withdrawal of alcohol/BZD 2. bulimia/anorexia 3. Use
of Zyban
 SNRIs: check BP
 Insomnia don’t use fluoxetine, bupropion later in the day; sedating medication take at
night (Remeron, paroxetine, trazodone)
 Mirtazapine: check weight and sleep (don’t choose if hypersomnia and overweight)
 SSRI: don’t use paroxetine for pregnant pt; don’t use SSRI if concern for sexual side
effect; watch out for citalopram/escitalopram dose due to Qtc prolongation; increases risk
of bleeding with anticoagulants (NSAIS, ginko biloba, , garlic, ginseng, glucosamine,
fish oil)
 Start low, go slow
 SSRI: Max dose of Celexa 40 mg/day (higher dose risk of QTc), Lexapro Max dose 20
mg/day (higher dose risk of QTc),), Max dose Prozac 80 mg/day; Max dose Zoloft 200
mg/day
 Low risk of sexual SE: bupropion, mirtazapine
 Sertraline preferred in Cardiac disease
 If failed antidepressant:
o 1. Ensure on 1st line agents for depression  If taking 1st line medication: check
Duration of therapy Dose—optimize if possible Switch medications or add
adjunct medication
o Switch: past medication hx? If only tried 1 SSRI, you may switch to another
SSRI/SNRI; check sleep, weight, CI
o Adjunct: only if partial response. Options include low dose AP e.g. abilify