selegiline

General Information

Selegiline (Eldepryl tablets, Zelapar orally disintegrating tablets) is a selective monoamine oxidase B (MAO-B) inhibitor used primarily as adjunct therapy for Parkinson disease; at antidepressant doses (≥30 mg/day) it becomes a nonselective MAOI and requires tyramine-restricted diet and drug-washout precautions.

Amphetamine metabolites contribute to wakefulness, so doses are scheduled in the morning and early afternoon to limit insomnia; patient counseling focuses on blood pressure monitoring and interaction avoidance.

Modern depression guidelines generally prefer the selegiline transdermal system for psychiatric use, reserving oral formulations for legacy regimens or when patients already receive selegiline for Parkinson disease and need additional mood benefit.

The contrast view and the Selegiline evidence feed can help contextualize conversion decisions and escalation planning toward antidepressant-dose MAOI therapy.

Because of interaction burden and dietary restrictions at antidepressant doses, many psychiatric patients convert to the transdermal formulation; oral selegiline largely remains in Parkinson clinics or legacy depression regimens where patients are already educated on MAOI precautions.

Mechanism of Action

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

Irreversibly inhibits MAO-B at ≤10 mg/day, augmenting central dopamine in Parkinson disease.

At higher doses inhibits MAO-A as well, boosting serotonin and norepinephrine but introducing classic MAOI cautions (tyramine sensitivity, serotonin syndrome).

• Selective MAO-B inhibition at standard doses reduces dopamine degradation.
• Loss of selectivity at ≥30 mg/day yields nonselective MAOI activity comparable to phenelzine or tranylcypromine.

Metabolism and Pharmacokinetics

• Rapid absorption; Zelapar ODT bypasses first-pass metabolism for higher bioavailability.
• Highly lipophilic with extensive CNS penetration.
• Hepatic CYP2B6, CYP2C19, and CYP3A4 convert selegiline to l-amphetamine and l-methamphetamine metabolites, which are renally eliminated.
• Parent half-life is ~10 hours, but MAO inhibition persists 1–2 weeks owing to irreversible binding, dictating 14-day washouts (5 weeks for fluoxetine).

Dosing and Administration

• Parkinson disease: 5 mg tablet with breakfast and lunch (max 10 mg/day); Zelapar ODT 1.25 mg each morning, titratable to 2.5 mg/day.
• Legacy antidepressant (off-label): begin 5 mg three times daily, titrate cautiously to 10 mg three times daily while enforcing tyramine restriction and monitoring blood pressure.
• Schedule doses early in the day to avoid insomnia; restart titration if treatment is interrupted for >1 week.

Monitoring & Labs

• Blood pressure during titration and after medication changes, with a clear plan for hypertensive crisis symptoms and emergency evaluation.
• Medication reconciliation to prevent accidental exposure to contraindicated serotonergic agents, sympathomimetics, or opioids.
• Sleep and activation (insomnia, jitteriness), especially because amphetamine-like metabolites can be stimulating.
• Mood elevation or mixed features in bipolar-spectrum illness; coordinate plans via the bipolar disorder hub when antidepressant-dose MAOI activity is expected.

Monitoring is primarily safety-focused (BP + interaction avoidance). Selegiline’s MAO inhibition persists for 1–2 weeks, so washout planning is as important as day-to-day dosing.

Adverse Effects

Interactions

• Absolute contraindications: serotonergic antidepressants, other MAOIs, linezolid, cyclobenzaprine, meperidine, tramadol, methadone, sympathomimetic appetite suppressants, and dextromethorphan.
• Allow ≥14-day washouts (5 weeks for fluoxetine) when transitioning to or from interacting medications.
• Avoid vasoconstrictor-containing local anesthetics and OTC sympathomimetics (pseudoephedrine, phenylephrine).

Other Useful Information

• Provide written lists of prohibited foods/medications and emphasize blood pressure monitoring during dose adjustments.
• Consider switching to the transdermal system when antidepressant efficacy is needed without extensive dietary restrictions.

References

1. Selegiline oral tablets prescribing information — DailyMed (2024)
2. Clinical management of oral MAOIs — Journal of Clinical Psychopharmacology (2022)
3. Monoamine oxidase inhibitors: Seriously underused in the treatment of major depression — Acta Psychiatrica Scandinavica (2024)
4. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
5. CANMAT recommendations for monoamine oxidase inhibitors — Canadian Journal of Psychiatry (2024)