Selegiline (Emsam for transdermal patch)

Class

Selective MAO-B inhibitor (oral and transdermal formulations)

Mechanism

Selectively inhibits monoamine oxidase B (MAO-B) at lower doses, increasing synaptic dopamine; at higher doses, non-selective MAO inhibition may occur, increasing monoamines including serotonin and norepinephrine.

FDA-Approved Use

Parkinson’s disease (PD) — oral formulation; major depressive disorder (MDD) — transdermal patch (Emsam)

Off-Label Use

Cognitive and behavioral symptoms in Parkinson’s disease (PD), apathy in dementia, depression in PD, treatment-resistant depression

Formulation

Oral tablets (5 mg, 10 mg), transdermal patch (6 mg/24h, titratable to 9 mg/24h or 12 mg/24h)

Titration

Patch starting dose 6 mg/24h, titratable to 9 or 12 mg/24h; oral dosing varies per indication

Dose Range

Patch 6–12 mg/24h

Kinetics

Transdermal delivery bypasses first-pass gastrointestinal metabolism, allowing selective MAO-B inhibition at lower doses

Common AEs

Insomnia, nausea, dizziness, headache

Serious/Rare AEs

Hypertensive crisis with tyramine-rich foods at higher doses (non-selective MAOI effect), serotonin syndrome risk with serotonergic agents

Monitoring

Monitor blood pressure, dietary tyramine intake, signs of serotonin syndrome especially when combined with serotonergic drugs

Black Box Warning

None specific, but caution advised due to MAOI effects and serotonin syndrome risk

Considerations

The transdermal patch formulation may benefit depressive symptoms with prominent apathy or cognitive slowing, particularly in Parkinson’s disease (PD) or vascular depression. Minimal anticholinergic or sedating effects make selegiline relatively well tolerated in older adults. Use caution when combining with serotonergic agents due to risk of serotonin syndrome, especially at higher patch doses.