EMSAM (selegiline transdermal system) is a monoamine oxidase inhibitor (MAOI) antidepressant delivered through a transdermal patch, offering a unique mechanism of action for patients with major depressive disorder (MDD) who have not achieved adequate response from other antidepressant therapies. By bypassing first-pass metabolism, EMSAM provides effective central nervous system monoamine oxidase inhibition while significantly reducing the dietary tyramine restrictions historically associated with oral MAOIs at its lower dosage strengths. This innovative delivery system represents a valuable option in the psychiatric pharmacopeia, particularly for cases of treatment-resistant depression, combining proven efficacy with an improved safety and tolerability profile.

Features

• Transdermal delivery system for continuous 24-hour selegiline administration
• Available in three dosage strengths: 6 mg/24 hr, 9 mg/24 hr, and 12 mg/24 hr
• Monoamine oxidase inhibitor (MAOI) class with selective MAO-B inhibition at lower doses and non-selective inhibition at higher doses
• Single-use patches measuring 20 cm² (6 mg), 30 cm² (9 mg), and 40 cm² (12 mg)
• Once-daily application with consistent pharmacokinetic profile
• FDA-approved for the treatment of major depressive disorder in adults

Benefits

• Provides an alternative mechanism of action for patients who have failed other antidepressant classes
• Transdermal administration avoids first-pass metabolism, reducing the formation of potentially problematic metabolites
• Lower doses (6 mg/24 hr) permit a liberalization of dietary tyramine restrictions compared to oral MAOIs
• Continuous drug delivery maintains stable plasma concentrations, potentially reducing peak-related side effects
• Demonstrated efficacy in reducing depressive symptoms in both short-term and maintenance treatment
• May be particularly effective for atypical depression features such as hypersomnia and fatigue

Common use

EMSAM is indicated for the treatment of major depressive disorder (MDD) in adults. It is typically prescribed when patients have not responded adequately to first-line antidepressant treatments such as SSRIs or SNRIs. The transdermal delivery system makes it particularly suitable for patients who experience gastrointestinal side effects with oral medications or those who prefer non-oral administration routes. Clinical use often involves patients with treatment-resistant depression, defined as failure to respond to at least two adequate antidepressant trials of different classes.

Dosage and direction

Initial dosage: 6 mg/24 hr applied once daily
Dosage adjustment: May increase to 9 mg/24 hr or 12 mg/24 hr after minimum of 2 weeks at lower dose if inadequate clinical response
Application site: Apply to dry, intact skin on upper torso (below neck and above waist), upper thigh, or outer surface of upper arm
Site rotation: Apply to a different site each day; do not apply to same site within 14 days
Preparation: Clean application site with soap and water; allow to dry completely before application
Wear time: Apply patch and wear for 24 hours; remove and discard used patch before applying new one
Duration of use: Continue as directed by healthcare provider; antidepressant effect may take several weeks to manifest fully

Precautions

• Dietary precautions: At 9 mg/24 hr and 12 mg/24 hr doses, patients must adhere to tyramine-restricted diet to prevent hypertensive crisis
• Application site reactions: Monitor for skin irritation, redness, or rash; rotate application sites to minimize reactions
• Orthostatic hypotension: May occur, particularly during dose titration; caution patients about rising slowly from sitting or lying position
• Serotonin syndrome: Risk exists, particularly when used with other serotonergic drugs; educate patients about symptoms
• Withdrawal symptoms: Avoid abrupt discontinuation; taper gradually under medical supervision
• Pregnancy and lactation: Use only if potential benefit justifies potential risk to fetus or infant
• Hepatic impairment: Use with caution in patients with liver disease; consider lower doses or alternative treatment
• Elderly patients: May be more sensitive to adverse effects; consider starting at lower end of dosage range

Contraindications

• Pheochromocytoma (due to risk of hypertensive crisis)
• Concomitant use with other MAOIs or within 14 days of discontinuing MAOI treatment
• Concomitant use with sympathomimetic amines, including amphetamines and cold products containing pseudoephedrine or phenylephrine
• Concomitant use with bupropion, buspirone, carbamazepine, cyclobenzaprine, dextromethorphan, meperidine, methadone, propoxyphene, tramadol, tapentadol, or St. John’s wort
• Concomitant use with serotonin precursors such as L-tryptophan
• History of hypersensitivity to selegiline or any component of the transdermal system
• Children and adolescents under 18 years of age (increased risk of suicidal thoughts and behaviors)

Possible side effects

Common (≥5% and greater than placebo):

• Application site reactions (redness, irritation, rash)
• Headache
• Insomnia
• Diarrhea
• Dry mouth
• Dyspepsia
• Pharyngitis

Less common but clinically significant:

• Orthostatic hypotension
• Dizziness
• Sedation
• Weight gain
• Sexual dysfunction
• Serotonin syndrome (requires immediate medical attention)
• Hypertensive crisis (particularly with dietary indiscretion at higher doses)
• Increased suicidal thoughts and behaviors (particularly in young adults)

Drug interaction

EMSAM has numerous clinically significant drug interactions due to its MAOI activity:

• Serotonergic drugs: Contraindicated with SSRIs, SNRIs, tricyclic antidepressants, triptans, lithium, tramadol, and other serotonergic agents (risk of serotonin syndrome)
• Sympathomimetics: Contraindicated with amphetamines, cold medications containing pseudoephedrine or phenylephrine, and other adrenergic agents
• CNS depressants: Enhanced sedative effects with alcohol, benzodiazepines, opioids, and other CNS depressants
• Tyramine-containing foods: Significant interaction at higher doses (9 mg/24 hr and 12 mg/24 hr) requiring dietary restriction
• Other MAOIs: Absolute contraindication due to risk of hypertensive crisis
• Dopaminergic agents: Potential for enhanced effects and side effects
• Hypotensive agents: May potentiate blood pressure-lowering effects

Missed dose

If a dose is missed, apply the patch as soon as possible on the same day. If remembered the next day, skip the missed dose and apply the next patch at the regular time. Do not apply extra patches to make up for a missed dose. Maintain the regular application schedule once daily. If multiple doses are missed, contact healthcare provider for guidance on resuming therapy.

Overdose

Symptoms of overdose may include hypertension, tachycardia, hyperpyrexia, agitation, confusion, hallucinations, seizures, coma, and cardiovascular collapse. Hypertensive crisis may manifest as severe headache, neck stiffness, nausea, vomiting, sweating, and dilated pupils. In case of suspected overdose, remove the patch immediately and seek emergency medical attention. Treatment is supportive and symptomatic; careful blood pressure management is essential. Avoid sympathomimetic drugs and consider alpha-adrenergic blockers for hypertension management.

Storage

Store at room temperature (20°C to 25°C/68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F). Keep in original pouch until time of use. Protect from moisture and direct sunlight. Do not store in bathroom or other humid areas. Keep out of reach of children and pets. Do not use if pouch is damaged or patches appear altered. Properly discard used patches by folding adhesive sides together and disposing in household trash away from children and pets.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. EMSAM is a prescription medication that should be used only under the supervision of a qualified healthcare provider. Individual response to treatment may vary. Patients should not make any changes to their medication regimen without consulting their healthcare provider. The complete prescribing information should be consulted before initiating therapy.

Reviews

Clinical trials demonstrate EMSAM’s efficacy in treating major depressive disorder. In a 6-week double-blind study, the 6 mg/24 hr dose showed statistically significant improvement in MADRS scores compared to placebo (p<0.05). Pooled analysis of multiple trials indicates response rates of approximately 40-50% with remission rates of 30-35% for the 6 mg/24 hr dose. Higher doses (9 mg/24 hr and 12 mg/24 hr) show increased efficacy but require dietary restrictions. Long-term maintenance studies demonstrate continued benefit with stable dosing over 52 weeks. Real-world evidence supports its utility in treatment-resistant populations, though dietary adherence remains a consideration at higher doses.