selegiline transdermal system

General Information

Selegiline transdermal system (EMSAM) delivers once-daily monoamine oxidase inhibition for adults with major depressive disorder, bypassing gastrointestinal metabolism to sustain MAO-B selectivity at 6 mg/24 h while minimizing tyramine sensitivity.

Higher doses (9 mg/24 h and 12 mg/24 h) expand to MAO-A inhibition, extending antidepressant efficacy but reintroducing dietary restrictions and hypertensive crisis risk.

Transdermal delivery avoids the emetic and gastrointestinal intolerance seen with oral selegiline and is considered when patients have failed or cannot tolerate multiple oral antidepressants.

The contrast view and the selegiline transdermal evidence feed can help contextualize escalation beyond 6 mg/24 h and crossover planning.

Used as a niche option for treatment-resistant depression where adherence to dietary restrictions and drug interaction management is feasible; higher cost and patch-specific counseling limit uptake.

Mechanism of Action

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

Selective inhibition of MAO-B at 6 mg/24 h increases synaptic dopamine and phenethylamine without significant gastrointestinal MAO-A inhibition, reducing tyramine pressor risk.

At 9 mg/24 h and 12 mg/24 h, clinically meaningful MAO-A inhibition occurs centrally and peripherally, enhancing serotonergic and noradrenergic tone and requiring tyramine dietary precautions.

• Selective MAO-B inhibition at 6 mg/24 h with minimal MAO-A involvement.
• Mixed MAO-A/B inhibition at ≥9 mg/24 h, providing broader monoaminergic augmentation.

Metabolism and Pharmacokinetics

• Steady-state is reached in approximately 5 days with once-daily application; patch delivers selegiline systemically over 24 hours.
• Bypasses first-pass hepatic metabolism, generating lower amphetamine metabolite exposure than oral selegiline tablets.
• Selegiline is extensively hepatic metabolized (CYP2B6, CYP2C19, CYP2A6) to desmethylselegiline and minor amphetamine metabolites; <1% is excreted unchanged.

Dosing and Administration

• Apply one 6 mg/24 h patch to dry, intact skin daily; rotate sites on the upper torso, upper thigh, or upper arm and avoid reuse within 14 days.
• Evaluate response after 4–6 weeks; if inadequate, titrate to 9 mg/24 h and, if necessary, to 12 mg/24 h. Apply each titration no sooner than every 2 weeks.
• Tyramine dietary restrictions are not required at 6 mg/24 h, but are mandatory at 9 mg/24 h and 12 mg/24 h.
• Discontinue serotonergic agents (SSRIs, SNRIs, TCAs, other MAOIs, linezolid, methylene blue, triptans) for the recommended washout period prior to initiation.

Monitoring & Labs

• Blood pressure and heart rate at baseline, after dose increases, and periodically (watch for hypertensive crisis).
• Dermatologic inspection of application sites with each visit.
• Mood, suicidality, and emergent mania/hypomania symptoms throughout therapy.

At 9 mg/24 h and 12 mg/24 h reinforce dietary tyramine precautions and document patient education.

Adverse Effects

Interactions

• Contraindicated with other MAO inhibitors, linezolid, methylene blue, and IV tryptophan.
• Serotonergic agents (SSRIs, SNRIs, TCAs, triptans, tramadol, dextromethorphan, St. John’s wort) increase serotonin syndrome risk; follow recommended washout periods.
• Sympathomimetic amines (pseudoephedrine, phenylephrine) and illicit stimulants may precipitate hypertensive crisis.
• Meperidine and other opioids with serotonergic properties are contraindicated; alternative analgesics are required.

Other Useful Information

• Press firmly for 30 seconds to ensure patch adhesion and avoid external heat sources (heating pads, saunas) that can accelerate absorption.
• Remove the patch prior to MRI or cardioversion due to the embedded metallic backing.
• Counsel patients to fold used patches adhesive to adhesive and dispose of in a manner that prevents accidental exposure.

References

1. EMSAM (selegiline transdermal system) prescribing information — DailyMed (2024)
2. Selegiline Transdermal System FOR THE Treatment OF Major Depressive Disorder: AN 8 Week, Double Blind, Placebo Controlled, Flexible Dose Titration Trial — Journal of Clinical Psychiatry (2006)