tranylcypromine

General Information

Tranylcypromine (Parnate) is an irreversible nonselective MAOI reserved for treatment-resistant depression and select bipolar depression cases, prescribed within MAOI-experienced programs that can manage dietary counselling, blood pressure surveillance, and emergency response.

Generic supply is intermittent; coordinate refills with pharmacies to prevent abrupt interruptions and reinforce written dietary and medication precautions at every visit.

The contrast view and the Tranylcypromine evidence feed can help weigh augmentation, ECT sequencing, and bipolar depression plans alongside the bipolar disorder hub.

Best suited for specialty care where clinicians can educate patients, provide wallet cards, and coordinate hypertensive crisis protocols (e.g., phentolamine on-call).

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, increasing synaptic serotonin, norepinephrine, dopamine, and trace amines; enzyme regeneration requires 10–14 days, mandating long washout intervals.

Amphetamine-like structure contributes to activation and mild sympathomimetic effects, necessitating early daytime dosing and monitoring for agitation.

• Irreversible inhibitor of MAO-A and MAO-B.

Metabolism and Pharmacokinetics

• Rapidly absorbed with peak plasma concentrations in ~2 hours; food delays Tmax but not overall exposure.
• Metabolized via hepatic CYP2A6/CYP2C19 pathways and acetylation; plasma half-life ~2 hours, yet pharmacodynamic MAO inhibition persists 7–14 days.
• Metabolites are primarily renally eliminated; use slower titration and closer monitoring in hepatic or renal impairment despite lack of formal dose adjustments.

Dosing and Administration

• Initiate 10 mg twice daily; increase by 10 mg/day every 1–2 weeks based on response and tolerability.
• Typical maintenance 30–60 mg/day divided BID; refractory cases may require up to 70–80 mg/day under specialist supervision.
• Schedule the final dose before mid-afternoon to reduce insomnia and activation.
• Maintain tyramine restriction throughout therapy and for 14 days post-discontinuation; observe ≥14-day washouts (5 weeks after fluoxetine) when switching serotonergic or sympathomimetic agents.

Monitoring & Labs

• Home blood pressure monitoring during titration and after medication changes, with clear hypertensive crisis instructions and emergency contact pathways.
• Medication reconciliation at every visit (prescription/OTC/herbal) to prevent accidental serotonergic or sympathomimetic exposure; enforce washout timing.
• Dietary adherence and teach-back review of tyramine-restricted foods (including restaurant and packaged-food pitfalls).
• Sleep/activation, anxiety, and orthostatic vitals; adjust dose timing and supportive measures to improve tolerability.
• Mood destabilization (mania/hypomania) and suicidality monitoring, especially in bipolar-spectrum illness; coordinate via the bipolar disorder hub.

Tranylcypromine monitoring prioritizes BP and interaction avoidance. Its activating profile can affect sleep and anxiety, so early follow-up and teach-back education are key.

Adverse Effects

Interactions

• Absolute contraindications include SSRIs/SNRIs, TCAs, mirtazapine, bupropion, buspirone, meperidine, tramadol, methadone, dextromethorphan, linezolid, methylene blue, sympathomimetic agents, and tyramine-rich foods.
• Require ≥14-day washout (≥5 weeks for fluoxetine) before initiating or discontinuing interacting medications.
• Advise patients to avoid OTC decongestants, weight-loss supplements, and excess caffeine; alert anesthesia providers prior to procedures to avoid indirect sympathomimetics.

Other Useful Information

• Provide wallet cards/medical alert identification listing MAOI therapy and emergency contact instructions.
• Encourage home blood pressure monitoring during titration and coordinate with pharmacies to secure consistent supply.
• Provide written “interaction check before adding anything new” guidance (cold medicines, cough syrups, supplements) and ensure the EHR carries a visible “MAOI alert” for other prescribers.

References

1. Tranylcypromine sulfate tablets prescribing information — DailyMed (2024)
2. Tranylcypromine FOR Treatment Resistant Depression: Clinical Considerations — Journal of Affective Disorders (2019)
3. Gillman2011 Maoi Pharmacology
4. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)
5. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
6. Monoamine oxidase inhibitors: Seriously underused in the treatment of major depression — Acta Psychiatrica Scandinavica (2024)