MAOIs for Depression: Mechanism, Indications, and Safety

Mechanism

Irreversible inhibition of monoamine oxidase (MAO-A and MAO-B) → ↑ synaptic serotonin, norepinephrine, dopamine, tyramine.

Indications

• Treatment-resistant depression (TRD)
• Atypical depression (mood reactivity, hypersomnia, hyperphagia, leaden paralysis, rejection sensitivity)
• Anxiety disorders (social phobia, panic)
• Parkinson's disease (MAO-B selective: selegiline, rasagiline)

Available Agents (US)

• Phenelzine (Nardil) — non-selective, irreversible
• Tranylcypromine (Parnate) — non-selective, irreversible
• Isocarboxazid (Marplan) — non-selective, irreversible
• Selegiline transdermal (Emsam) — MAO-B selective at low dose; MAO-A/B at high dose

Dietary Restrictions (Non-selective MAOIs)

Tyramine-restricted diet to prevent hypertensive crisis: avoid aged cheeses, cured meats, fermented foods, tap beer, soy products, overripe fruits. Selegiline patch ≤6 mg/24h: no diet restriction.

Drug Interactions

• Absolute contraindications: SSRIs, SNRIs, TCAs, meperidine, dextromethorphan, linezolid, methylene blue, other MAOIs — risk serotonin syndrome.
• Washout periods: 2 weeks (5 weeks fluoxetine) before/after MAOI.
• Sympathomimetics (pseudoephedrine, amphetamines) → hypertensive crisis.

Monitoring

BP, weight, mood, suicidal ideation. Patient education card essential.