Pharmaceutical

Selegiline

(R)-N-Methyl-1-phenylpropan-2-amine

Evidence TierAWADA PROHIBITED

tuneTypical Dose

5–10 mg per day (oral); 6 mg/24h (transdermal)

watchEffect Window

1-2 weeks for neurological/mood effects; MAO-B inhibition is irreversible (enzyme recovery over 2-3 weeks).

lockCompliance

WADA PROHIBITED

Overview

Clinical Summary

Selegiline is a prescription MAO-B inhibitor used in Parkinson’s disease and some depression formulations. It is used to enhance dopaminergic signaling by reducing dopamine breakdown, affecting motor and mood symptoms.

Evidence supports improved Parkinson’s motor symptoms and reduced off time in some patients, particularly in early disease. Certain formulations have antidepressant efficacy in selected contexts. Minority research explores neuroprotection, but disease-modifying effects remain uncertain. Benefits require careful management of drug interactions and patient selection, since adverse effects and contraindications can limit tolerability.

Irreversible, selective MAO-B inhibitor at low doses; prevents breakdown of dopamine and phenylethylamine. Loses MAO-B selectivity at higher doses, also inhibiting MAO-A. Metabolizes to l-amphetamine and l-methamphetamine.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Delays need for levodopa in early Parkinson's disease
  • Effective treatment for major depressive disorder (transdermal EMSAM patch)

Secondary Outcomes

  • Neuroprotective and anti-aging effects (animal data, limited human evidence)
  • Cognitive enhancement via increased dopamine and PEA levels

Safety

Contraindications and Interactions

Contraindications

  • Concurrent SSRIs or SNRIs
  • Meperidine
  • Other MAOIs
  • Concurrent serotonergic agents

Side effects

  • Insomnia
  • Nausea
  • Dizziness
  • Dry mouth
  • Orthostatic hypotension

Interactions

  • SSRIs (absolute contraindication , serotonin syndrome)
  • SNRIs (absolute contraindication)
  • Meperidine/dextromethorphan/tramadol (serotonergic crisis)
  • Sympathomimetics (hypertensive crisis)
  • Tyramine-rich foods at doses >10 mg/day

Avoid if

  • Currently taking antidepressants
  • On meperidine or other MAOIs
  • Unable to comply with dietary restrictions at higher doses

Evidence

Study-level References

selegiline-SRC-001RCT (DATATOP study)
Sourceopen_in_new

The Parkinson Study Group. "Effect of Deprenyl on the Progression of Disability in Early Parkinson's Disease." N Engl J Med. 1989.

Population: Early Parkinson's Disease patients

Key findings: Deprenyl (Selegiline) delayed the onset of disability necessitating levodopa therapy by nearly a year compared to placebo in early PD patients.

Paper content

Deprenyl (Selegiline) delayed the onset of disability necessitating levodopa therapy by nearly a year compared to placebo in early PD patients.

selegiline-SRC-002Systematic review and meta-analysis.
Sourceopen_in_new

Bene MR. L-deprenyl extends lifespan across mammalian species: A meta-analysis of 22 longevity experiments. Ageing Res Rev. 2025;112:102873. doi:10.1016/j.arr.2025.102873. PMID:40816452.

Population: Rodent models across 22 lifespan experiments spanning 27 years of research.

Dose protocol: L-deprenyl at varying doses across 22 rodent longevity experiments

Key findings: Meta-analysis of 22 mammalian lifespan experiments found L-deprenyl significantly increases average lifespan (SMD 0.6773, P=0.0002). Higher doses and later treatment initiation produced larger effects. Dog data showed no significant effect after adjustment.

Notes: Animal data only. No human longevity trials exist for selegiline.

Paper content

This meta-analysis pooled 22 rodent longevity experiments conducted over 27 years to assess whether L-deprenyl (selegiline) extends mammalian lifespan. The overall effect was statistically significant with a moderate effect size (SMD 0.6773, P=0.0002). Higher doses and later treatment initiation were associated with larger longevity gains. A reanalyzed dog survival study showed no significant effect after adjusting for age and sex. The findings provide the most comprehensive quantitative summary of L-deprenyl lifespan data in animals, but the relevance to human aging remains speculative given the absence of controlled human longevity trials.

selegiline-SRC-003Systematic review and meta-analysis.
Sourceopen_in_new

Rossano F, Caiazza C, Sobrino A, et al. Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations. Eur Neuropsychopharmacol. 2023;72:60-78. doi:10.1016/j.euroneuro.2023.03.012. PMID:37087864.

Population: Patients with depressive disorders, schizophrenia, or ADHD across included trials.

Dose protocol: Oral and transdermal selegiline across psychiatric disorder trials

Key findings: Systematic review and meta-analysis found selegiline outperformed placebo for depressive symptoms, with particular efficacy in atypical depression. No benefit for schizophrenia or ADHD. Generally well tolerated with insomnia and dry mouth as common side effects.

Notes: Confirms antidepressant efficacy and defines the psychiatric indications where selegiline does and does not work.

Paper content

This systematic review and meta-analysis assessed selegiline efficacy across psychiatric disorders. Selegiline outperformed placebo in reducing depressive symptoms, with particular efficacy for atypical depression. It showed no benefit over placebo for schizophrenia or ADHD symptoms. Common adverse effects included insomnia, dry mouth, and application-site reactions with the transdermal patch. The drug was generally well tolerated. The analysis confirms selegiline as an effective antidepressant option but does not support its use for other psychiatric indications.

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