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selegiline transdermal system

Adjunctive therapy

Brand: EMSAM

Published 2026-02-16 · Last reviewed 2026-02-23 · 5 references

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

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: Apply one 6 mg/24 h patch to dry, intact skin daily; rotate sites on the upper torso, upper thigh, or upper arm and do not use the same site on consecutive days.·Half-life: Single-dose mean 25 h·LAI available: No

Class: Adjunctive therapy
Typical dose: Apply one 6 mg/24 h patch to dry, intact skin daily; rotate sites on the upper torso, upper thigh, or upper arm and do not use the same site on consecutive days.
Half-life: Single-dose mean 25 h
LAI available: No

Quick answers

What is selegiline transdermal system?: 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.
What is EMSAM?: EMSAM is a brand name for selegiline transdermal system.
What is EMSAM (selegiline transdermal system) used for?: Label indications include: Major depressive disorder in adults.
What drug class is EMSAM (selegiline transdermal system)?: MAOI Antidepressant.
What is the mechanism of action of EMSAM (selegiline transdermal system)?: Selective MAO-B inhibitor at 6 mg/24 h; loses selectivity at higher doses providing MAO-A inhibition.
What strengths does EMSAM (selegiline transdermal system) come in?: Transdermal patches: 6 mg/24 h, 9 mg/24 h, 12 mg/24 h.

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

U.S. approvals

Major depressive disorder (adults) (2006)

Formulations & strengths

Transdermal patches: 6 mg/24 h, 9 mg/24 h, 12 mg/24 h.

Generic availability

Brand only (EMSAM) in the United States.

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.

View labelExact

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 & 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 & 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 do not use the same site on consecutive 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

FDA boxed warnings

Antidepressants increase the risk of suicidality in children, adolescents, and young adults; monitor closely during initiation and dose changes.

Common side effects (≥10%)

Application-site reactions: Erythema, pruritus, or burning occurs in 20–30% of patients; rotate sites and avoid occlusive dressings.
Insomnia: Observed in ~12–14%; consider morning application and assess for activating co-medications.
Dry mouth: Reported in ~9%; counsel on hydration and oral hygiene.

Other notable effects

Hypertensive crisis with tyramine excess or sympathomimetic exposure, particularly at 9 mg/24 h and 12 mg/24 h.
Serotonin syndrome with concomitant serotonergic agents.
Orthostatic hypotension and syncope, especially in volume depletion or antihypertensive co-therapy.
Hypomania/mania activation in bipolar spectrum disorders—coordinate with mood stabilizers and consult the bipolar disorder hub.

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

Related hubs:SMI toolkit·Support resources