Prescription ·Strong evidence ·Reviewed May 2026
Selegiline is an irreversible MAO-B inhibitor used orally as adjunctive therapy in Parkinson disease and as a transdermal system for major depressive disorder. At recommended Parkinson doses it is relatively selective for MAO-B, but selectivity can diminish at higher exposures, increasing risks of hypertensive crisis and serotonergic drug interactions. The transdermal antidepressant product carries the antidepressant boxed warning for suicidal thoughts and behaviors in younger patients.
The bottom line
Evidence rating strong. Most-documented uses: adjunctive treatment of parkinson disease in patients receiving levodopa/carbidopa, reduction in parkinson off time, treatment of major depressive disorder with the transdermal system. 3 sources indexed (1989–2025), with 5 interaction records on file.
Core mechanism
Selegiline irreversibly inhibits monoamine oxidase B, reducing dopamine metabolism in the brain and increasing dopaminergic activity in Parkinson disease. Transdermal dosing produces higher systemic selegiline exposure and antidepressant effects through broader central monoamine modulation while partly bypassing gut first-pass MAO-A inhibition at the lowest patch dose. Loss of MAO selectivity, serotonergic combinations, sympathomimetics, and tyramine-rich foods at higher-risk doses can produce severe toxicity.1,2
Oral capsules are usually taken with breakfast and lunch to reduce insomnia. Orally disintegrating tablets should be taken before breakfast without liquid. Dietary tyramine restriction is required for higher-dose transdermal patches and if MAO-A inhibition is clinically relevant.3
Selegiline can act as a monoamine oxidase inhibitor depending on formulation and dose. Systemic or higher-dose MAOI exposure can reduce tyramine breakdown, so high-tyramine foods may trigger sudden, severe blood-pressure elevation and hypertensive crisis.
Recommendation: Follow the prescriber-specific tyramine restrictions for your selegiline formulation and dose. Avoid high-tyramine foods whenever MAOI dietary restrictions apply.
5-HTP increases serotonin synthesis while Selegiline reduces monoamine breakdown. Combining them can cause dangerous serotonergic excess and serotonin syndrome.
Recommendation: Do NOT combine 5-HTP with Selegiline. Use only if the prescriber managing Selegiline explicitly directs it and provides washout instructions.
L-Tryptophan feeds serotonin synthesis while Selegiline reduces serotonin breakdown, increasing risk of serotonin syndrome.
Recommendation: Do NOT combine L-tryptophan with Selegiline unless specifically directed and monitored by the prescriber managing Selegiline.
St. John's Wort is explicitly contraindicated with selegiline transdermal labeling and is unsafe with MAOI therapy because of serotonergic effects.
Recommendation: Do not use St. John's Wort with selegiline.
Rhodiola is promoted for stimulant and monoaminergic effects. Combining it with MAO-B inhibition may increase agitation, insomnia, blood pressure, or serotonergic symptoms.
Recommendation: Avoid unless the prescriber specifically approves; monitor blood pressure and neuropsychiatric symptoms if exposure has already occurred.
Numbered references. Citations throughout the page link here.
The DATATOP trial supported clinical benefit of deprenyl in early Parkinson disease, though interpretation included symptomatic effects.
Labeling describes Parkinson indication, 10 mg/day dosing, loss of selectivity concerns, and serious reactions with meperidine and serotonergic drugs.
The transdermal label documents MDD dosing, suicidal thoughts boxed warning, contraindicated drugs, and tyramine diet requirements at 9 and 12 mg/24 hour doses.
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