phenelzine

General Information

Phenelzine (Nardil) is a non-selective, irreversible monoamine oxidase inhibitor reserved for treatment-resistant depression, atypical depression, and select anxiety disorders managed in specialty settings.

Because it permanently inactivates MAO-A/B, strict dietary tyramine restrictions, comprehensive interaction screening, and crisis planning are mandatory throughout therapy.

The contrast view and the Phenelzine evidence feed can help align diet, washout, and titration planning across MAOIs.

Phenelzine is safest when prescribed within an MAOI-experienced program that can provide written diet/interaction lists, teach-back education, and an emergency plan for hypertensive symptoms.

Many MAOI programs use standardized food/medication checklists and pharmacy review to reduce interaction errors; MAO inhibition persists for 1–2 weeks after discontinuation, which shapes washout planning.

Coordinate pharmacy access, provide medical alert identification, and review emergency responses for hypertensive crises or serotonin syndrome at every visit.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Irreversibly inhibits MAO-A and MAO-B, elevating serotonin, norepinephrine, dopamine, and phenethylamine; enzyme activity recovers only after new synthesis (1–2 weeks post discontinuation).

• Non-selective irreversible MAOI.

Metabolism and Pharmacokinetics

• Rapidly absorbed with plasma half-life ≈12 h; pharmacodynamic inhibition persists 2–3 weeks due to irreversible binding.
• Metabolized primarily via hepatic acetylation (NAT2); slow acetylators exhibit higher exposure.
• Metabolites are excreted chiefly in urine; use cautiously in hepatic impairment with periodic liver monitoring.

Dosing and Administration

• Start 15 mg three times daily; increase by 15 mg increments every few days to 45 mg/day (week 1), 60 mg/day (week 2), and up to 75–90 mg/day divided for optimal response.
• Once stabilized, taper to the lowest effective maintenance dose (often 15 mg BID/TID) while maintaining dietary restrictions.
• Maintain tyramine-restricted diet and interaction precautions during therapy and for at least 14 days after discontinuation (30 days for fluoxetine transitions).

Monitoring & Labs

• Home blood pressure monitoring during titration (and after medication changes), with a clear plan for hypertensive crisis symptoms and emergency evaluation.
• Medication reconciliation at every visit (prescription, OTC, herbal) to prevent accidental exposure to serotonergic agents or sympathomimetics; reinforce washout timing.
• Dietary adherence and tyramine-risk counseling using teach-back; review common restaurant and packaged-food pitfalls.
• Orthostatic vitals, falls risk, and sleep/activation symptoms; adjust dose timing and supportive treatments to improve adherence.
• Liver-injury symptoms and periodic LFTs when clinically indicated; monitor for rare peripheral neuropathy and consider vitamin B6 support if symptoms develop.
• Mood destabilization (mania/hypomania) and suicidality monitoring during initiation and dose changes, especially in bipolar-spectrum illness.

Phenelzine monitoring is primarily safety-focused (BP + interaction and diet avoidance) for patients and caregivers. Because MAO inhibition persists after stopping, washout planning is as important as day-to-day dosing.

Adverse Effects

Interactions

• Contraindicated with SSRIs, SNRIs, TCAs, other MAOIs, mirtazapine, bupropion, buspirone, meperidine, tramadol, methadone, dextromethorphan, linezolid, methylene blue, atomoxetine, and sympathomimetics; observe ≥14-day washouts (≥30 days for fluoxetine).
• Strictly avoid high-tyramine foods (aged cheeses, cured meats, soy products, tap beers) and OTC decongestants/stimulants; provide detailed dietary and medication lists.

Other Useful Information

• Medical alert identification, wallet interaction cards, and emergency protocols for hypertensive symptoms are commonly used.
• Seated/standing blood pressure, weight, mood, and liver enzymes are commonly tracked; dietitian support can reinforce dietary education.
• Keep a visible “MAOI alert” in the medical record and coordinate with primary care, dentistry, and anesthesia teams to avoid contraindicated analgesics and decongestants.

References

1. Phenelzine sulfate tablets prescribing information — DailyMed (2025)
2. Gillman2011 Maoi Pharmacology
3. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)
4. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
5. Monoamine oxidase inhibitors: Seriously underused in the treatment of major depression — Acta Psychiatrica Scandinavica (2024)