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Phenelzine (Nardil)

MAOI • Last reviewed 2025-09-27

General information

Phenelzine is an irreversible nonselective MAOI reserved for treatment-resistant or atypical depression. It requires strict adherence to tyramine-restricted diet and medication washouts to prevent hypertensive crisis.

Because the pharmacologic effect persists 1–2 weeks, careful planning is required when switching therapies.

Common adverse effects include weight gain, peripheral edema, orthostatic hypotension, and sexual dysfunction.

Abrupt hypertensive crisis presents with throbbing headache, palpitations, and neck stiffness—patients should carry emergency instructions.

Dosing & administration

Start 15 mg three times daily; increase by 15 mg every few days to 45 mg twice daily (90 mg/day) as tolerated.

Reduce dose in hepatic impairment; avoid in patients with pheochromocytoma or cardiovascular disease requiring sympathomimetics.

Mechanism of action

Irreversibly inhibits MAO-A and MAO-B, increasing synaptic serotonin, norepinephrine, and dopamine.

Metabolism & pharmacokinetics

Peak plasma levels within 1 hour; half-life ~12 h but enzyme inhibition lasts 7–14 days. Metabolized via acetylation (NAT2).

Drug interactions

Absolute contraindication with other serotonergic or sympathomimetic drugs (SSRIs, TCAs, meperidine, dextromethorphan).

Avoid tyramine-rich foods (aged cheese, cured meats, tap beer).

Use caution with antihypertensives or anesthetics; consult MAOI interaction lists.

Monitoring & safety checks

  • Blood pressure (baseline, each visit)

  • Weight monitoring (risk of gain)

  • Education on diet, drug restrictions, emergency plan

Discontinuation guidance

Taper by 15 mg every few days; maintain tyramine restrictions for 14 days after last dose.

References

  1. Phenelzine Prescribing Information — DailyMed
  2. Consensus recommendations for MAOI safety and dietary management — Journal of Clinical Psychopharmacology (2022)
  3. CANMAT recommendations for monoamine oxidase inhibitors — Canadian Journal of Psychiatry (2024)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.