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selegiline

Adjunctive therapy

Brands: Eldepryl, Zelapar

Published 2025-09-28 · Last reviewed 2025-10-05 · 5 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: 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.·Half-life: Single-dose mean 10 h·LAI available: No

Class: Adjunctive therapy
Typical dose: 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.
Half-life: Single-dose mean 10 h
LAI available: No

Quick answers

What is selegiline?: 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.
What is Eldepryl?: Eldepryl is a brand name for selegiline (other brands: Zelapar).
What is Eldepryl (selegiline) used for?: Label indications include: Adjunct for major depressive disorder (under EMSAM brand) and Parkinson disease (oral formulations).
What drug class is Eldepryl (selegiline)?: MAOI Antidepressant.
What is the mechanism of action of Eldepryl (selegiline)?: Selective MAO-B inhibitor at low doses; becomes nonselective at 10 mg/day, increasing serotonin and norepinephrine.
What strengths does Eldepryl (selegiline) come in?: Tablets: 5 mg scored.

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

U.S. approvals

Adjunct to levodopa/carbidopa in Parkinson disease (1989)

Formulations & strengths

Tablets: 5 mg scored.
Orally disintegrating tablets: 1.25 mg, 2.5 mg.

Generic availability

Both tablets and ODTs are available as generics, though ODT supply can be intermittent.

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.

View labelExact

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 & 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 & 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

FDA boxed warnings

Risk of hypertensive crisis with tyramine-containing foods or sympathomimetics when MAO-A is inhibited; provide dietary education and emergency instructions.

Common side effects (≥10%)

Insomnia/activation: Stimulant-like metabolites can disrupt sleep; dose in the morning and early afternoon.
Orthostatic hypotension: Monitor seated/standing blood pressure, especially when combined with levodopa.
Nausea: Often transient; taking with food (tablets) or adjusting timing can help.

Other notable effects

Serotonin syndrome with serotonergic agents—observe mandatory washouts before/after therapy.
Hallucinations or confusion in Parkinson populations, particularly when combined with dopaminergic therapy.
Mania/hypomania activation can occur in bipolar spectrum disorders; coordinate with mood stabilizers and consult the bipolar disorder hub before escalating doses.
Potential for false-positive amphetamine screens because of metabolites.

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

Related hubs:SMI toolkit·Support resources