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MAOI (Irreversible Monoamine Oxidase Inhibitor) Pregnancy: Avoid — risk to fetus (neonatal hypotension, growth retardation). Use under specialist guidance only if no alternative.

Phenelzine

Brand names: Nardil

Adult dose

Dose: Depression (treatment-resistant / atypical): 15mg TDS initially; increase over 2–4 weeks to 15–30mg TDS; usual maintenance 15mg BD–TDS. After remission, reduce slowly to minimum effective dose (often 15mg OD).
Route: Oral
Frequency: Two to three times daily
Max: 90mg daily (under specialist supervision)
Irreversible, non-selective MAO-A and MAO-B inhibitor. Requires 14-day washout before starting any serotonergic drug. Mandatory dietary tyramine restriction (aged cheese, cured meats, fermented foods, Marmite, soy sauce, broad beans) — 'cheese reaction' risk. Used only by specialists for treatment-resistant or atypical depression unresponsive to other antidepressants.

Paediatric dose

Route: Oral
Frequency: Three times daily
Max: Not applicable
Not licensed under 18 years. Seek specialist child and adolescent psychiatry opinion. Rarely used in this age group.

Dose adjustments

Renal

Use with caution — limited data. Avoid in severe renal impairment.

Hepatic

Contraindicated in hepatic impairment — hepatotoxicity risk; abnormal LFTs are a contraindication.

Clinical pearls

  • 14-day washout in BOTH directions: wait 14 days after stopping phenelzine before starting any serotonergic drug; wait 14 days after stopping most antidepressants before starting phenelzine (except fluoxetine — 5-week washout required due to long half-life)
  • Dietary counselling is mandatory — provide written tyramine-restricted diet list; ensure patient understands the risk of hypertensive crisis from dietary tyramine
  • Antidote for hypertensive crisis (cheese reaction): IV phentolamine (alpha-blocker) or oral nifedipine; avoid beta-blockers alone (leaves alpha-receptor unopposed)
  • Phenelzine is reserved for treatment-resistant depression under specialist supervision — particularly effective in atypical depression (reverse vegetative features: hypersomnia, hyperphagia, mood reactivity, rejection sensitivity)

Contraindications

  • Hepatic impairment
  • Cerebrovascular disease
  • Phaeochromocytoma
  • Concomitant SSRIs, SNRIs, TCAs, other MAOIs, pethidine, tramadol, sympathomimetics, dextromethorphan — risk of life-threatening interactions
  • Hypersensitivity to phenelzine

Side effects

  • Hypertensive crisis (cheese reaction — dietary tyramine)
  • Orthostatic hypotension (common)
  • Dizziness, headache
  • Insomnia or sedation
  • Oedema
  • Sexual dysfunction
  • Weight gain
  • Hepatotoxicity (rare)
  • Hyperpyrexia
  • Myoclonic jerks

Interactions

  • SSRIs, SNRIs, TCAs, other MAOIs — serotonin syndrome / hypertensive crisis — CONTRAINDICATED; 14-day washout required (both ways)
  • Pethidine — potentially fatal (excitatory reaction — hyperpyrexia, seizures, coma); all opioids should be used with caution (morphine/fentanyl safest alternatives at lowest doses)
  • Sympathomimetics (ephedrine, pseudoephedrine, OTC cold remedies) — hypertensive crisis
  • Dextromethorphan (in cough remedies) — serotonin syndrome
  • Levodopa — hypertension
  • Insulin/antidiabetics — phenelzine enhances hypoglycaemic effect

Monitoring

  • Blood pressure (orthostatic and lying)
  • LFTs (phenelzine is hepatotoxic — monitor at baseline and periodically)
  • Dietary adherence review at each appointment
  • Mood response

Reference: BNFc; BNF 90; Maudsley Prescribing Guidelines (13th Ed). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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