BSN Tracker

phenelzine

Brand: Nardil

⚠ BBW Beers Criteria Prototype Drug
Drug Class: monoamine oxidase inhibitor (MAOI)
Drug Family: antidepressant
Subclass: irreversible, non-selective MAOI
Organ Systems: cns

Mechanism of Action

Irreversibly inhibits both MAO-A and MAO-B, enzymes responsible for metabolizing monoamines (serotonin, norepinephrine, dopamine, tyramine). The resulting increase in synaptic monoamine levels produces antidepressant effects. Irreversible inhibition means restoration of MAO activity requires synthesis of new enzyme, taking 2-3 weeks.

MAO-A (monoamine oxidase A)MAO-B (monoamine oxidase B)

Indications

  • major depressive disorder (particularly atypical features, treatment-resistant)
  • panic disorder
  • social anxiety disorder

Contraindications

  • concurrent serotonergic drugs
  • concurrent sympathomimetics
  • pheochromocytoma
  • congestive heart failure
  • tyramine-rich foods during and 14 days after discontinuation

Adverse Effects

Common

  • orthostatic hypotension
  • insomnia
  • weight gain
  • sexual dysfunction
  • dry mouth
  • constipation
  • edema

Serious

  • hypertensive crisis with tyramine ingestion
  • serotonin syndrome with serotonergic drugs
  • hypoglycemia (potentiates insulin)
  • hepatotoxicity (rare)

Pharmacokinetics (ADME)

Absorption well absorbed orally
Distribution widely distributed; crosses BBB
Metabolism hepatic acetylation; N-acetylation rate is genetically determined (fast vs. slow acetylators)
Excretion primarily renal
Half-life 11.6 hours (but enzyme inhibition outlasts the drug itself)
Onset 2-4 weeks for antidepressant effect; MAO inhibition within 24-48 hours
Peak 1-2 hours
Duration pharmacodynamic effect persists 2-3 weeks after discontinuation
Protein Binding minimal
Vd not well characterized

Drug Interactions

Drug / Agent Mechanism Severity
SSRIs, SNRIs, TCAs, tramadol, meperidine, dextromethorphan serotonin syndrome; potentially fatal contraindicated
sympathomimetics (ephedrine, pseudoephedrine, cocaine) hypertensive crisis via excessive norepinephrine release contraindicated
tyramine-rich foods (aged cheese, cured meats, fermented beverages) hypertensive crisis via unmetabolized intestinal tyramine entering systemic circulation contraindicated
insulin and oral antidiabetics potentiation of hypoglycemia via increased insulin sensitivity major

Nursing Considerations

  1. Extensive dietary education is mandatory before initiating: patients must avoid tyramine-rich foods (aged cheeses, cured meats, fermented products, tap beer, chianti wine, broad beans) throughout therapy and for 14 days after discontinuation.
  2. Teach patient to recognize hypertensive crisis: sudden severe headache, neck stiffness, palpitations, visual disturbances — go immediately to emergency department; have patient carry a MAOI medication card.
  3. A 14-day washout period is required before switching from an MAOI to any serotonergic drug (SSRIs, SNRIs, TCAs, tramadol, meperidine, triptans); document last dose date explicitly.
  4. Monitor blood pressure routinely for orthostatic hypotension; phenelzine has more orthostatic hypotension than other MAOIs.

Clinical Pearls

  • MAOIs are considered among the most effective antidepressants for atypical depression (characterized by mood reactivity, hypersomnia, leaden paralysis, hyperphagia, rejection sensitivity) and are frequently more effective than SSRIs for this presentation.
  • The dietary restriction of tyramine is not a side effect per se but a pharmacodynamic consequence: intestinal MAO-A normally breaks down dietary tyramine; inhibition allows tyramine to enter systemic circulation and trigger massive norepinephrine release from adrenergic neurons, causing hypertensive crisis.

Safety Profile

Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Major Depressive Disorder (particularly Atypical Features, Treatment-resistant) Monoamine Oxidase Inhibitor (MAOI) Panic Disorder Social Anxiety Disorder
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