EMSAM (selegiline transdermal system) represents a significant advancement in the pharmacological management of major depressive disorder (MDD). As the first and only transdermal monoamine oxidase inhibitor (MAOI) approved by the FDA, it offers a unique mechanism of action that bypasses many of the historical limitations associated with oral MAOIs. This innovative delivery system provides continuous drug delivery over 24 hours, ensuring stable plasma concentrations and potentially improving therapeutic outcomes for patients who have not achieved satisfactory response with other antidepressant classes. Its development marks a critical evolution in neuropsychiatric treatment, combining established efficacy with a modernized administration profile.

Features

• Contains selegiline, a selective monoamine oxidase-B inhibitor
• Transdermal delivery system providing controlled, continuous medication release over 24 hours
• Available in three dosage strengths: 6 mg/24 hr, 9 mg/24 hr, and 12 mg/24 hr
• Thin, multi-layered patch designed for adhesion and patient comfort
• Bypasses first-pass metabolism, potentially reducing hepatic strain
• Once-daily application simplifies dosing regimen

Benefits

• Provides effective relief from depressive symptoms without the dietary restrictions typically associated with MAOIs at lower doses (6 mg/24 hr)
• Offers an alternative for treatment-resistant depression when other antidepressants have failed
• Minimizes gastrointestinal side effects common with oral antidepressants through transdermal absorption
• Maintains consistent drug levels, potentially reducing peak-to-trough fluctuations and associated side effects
• May demonstrate faster onset of action compared to some conventional antidepressants
• Reduces pill burden and may improve adherence through once-daily application

Common use

EMSAM is primarily indicated for the treatment of major depressive disorder (MDD) in adults. It is particularly valuable for patients who have not responded adequately to other antidepressant classes, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). The transdermal system may be especially beneficial for patients who experience significant gastrointestinal side effects with oral medications or those with compliance challenges related to multiple daily dosing. Clinical studies have demonstrated its efficacy in both acute treatment and maintenance therapy for MDD.

Dosage and direction

The recommended starting dosage is 6 mg/24 hours, applied once daily. The patch should be applied to dry, intact skin on the upper torso (below the neck and above the waist), upper thigh, or outer surface of the upper arm. Application sites should be rotated with each new patch to minimize skin irritation. The dosage may be increased to 9 mg/24 hours or 12 mg/24 hours after appropriate clinical assessment, though dietary modifications become necessary at doses exceeding 6 mg/24 hours. Patches should be worn for exactly 24 hours and replaced at approximately the same time each day.

Precautions

Patients should be carefully monitored for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Caution is advised when prescribing for patients with bipolar disorder. Blood pressure should be monitored regularly, particularly during dose escalation. Patients should be advised about the potential for orthostatic hypotension. The patch may cause application site reactions, and patients should be instructed on proper skin care and rotation techniques. Avoid exposure of application site to external heat sources, as this may increase drug absorption.

Contraindications

EMSAM is contraindicated in patients with pheochromocytoma, as MAOIs may precipitate hypertensive crisis. Concomitant use with meperidine is absolutely contraindicated due to risk of serotonin syndrome and other adverse reactions. The 9 mg/24 hr and 12 mg/24 hr doses are contraindicated with concomitant use of sympathomimetic amines, including over-the-counter cough and cold preparations. Concurrent use with other MAOIs or within 14 days of discontinuing other MAOIs is contraindicated. Use with bupropion is contraindicated due to increased risk of hypertension.

Possible side effects

Common adverse reactions (≥5% and twice placebo) include application site reactions, headache, insomnia, diarrhea, dry mouth, dyspepsia, and rash. Less frequently reported side effects include orthostatic hypotension, sexual dysfunction, weight changes, and increased sweating. As with other antidepressants, EMSAM carries a boxed warning regarding increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults. Serotonin syndrome, though rare, represents a potentially serious adverse effect requiring immediate medical attention.

Drug interaction

Significant interactions occur with serotonergic drugs (SSRIs, SNRIs, triptans, tramadol, tryptophan), which may precipitate serotonin syndrome. Concomitant use with sympathomimetic amines may cause hypertensive crisis at higher doses. Concurrent use with dextromethorphan may result in psychosis or abnormal behavior. EMSAM may potentiate the effects of CNS depressants including alcohol, barbiturates, and benzodiazepines. Tyramine-rich foods require restriction at doses above 6 mg/24 hr due to risk of hypertensive crisis.

Missed dose

If a dose is missed, the patient should apply the patch as soon as remembered unless it is almost time for the next application. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not apply extra patches to make up for missed doses. If multiple doses are missed, medical consultation is recommended before resuming treatment, as dose adjustment may be necessary.

Overdose

Symptoms of overdose may include hypertension, tachycardia, hyperpyrexia, agitation, confusion, hallucinations, and seizures. Serotonin syndrome manifestations may include mental status changes, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms. Management involves immediate removal of the patch, supportive care, and symptomatic treatment. Benzodiazepines may be used for agitation or seizures. Cyproheptadine may be considered for serotonin syndrome. Intensive monitoring of vital signs and cardiac function is essential.

Storage

Store at room temperature between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F). Keep in original pouch until time of use. Protect from moisture and humidity. Keep out of reach of children and pets. Used patches should be folded with adhesive sides together and disposed of properly to prevent accidental exposure.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions should be made in consultation with a qualified healthcare professional familiar with the patient’s specific medical history and current condition. Individual responses to medication may vary, and only a healthcare provider can determine the appropriate treatment course based on comprehensive clinical assessment.

Reviews

Clinical trials demonstrate significant improvement in Hamilton Depression Rating Scale scores compared to placebo. Many patients report improved quality of life and functional capacity. Healthcare providers note particular value in treatment-resistant cases where other options have failed. Some patients appreciate the convenience of transdermal administration compared to oral medications. Dermatological reactions at application sites represent the most frequently reported practical concern, though these are typically mild to moderate in severity. Long-term studies support maintained efficacy with continued use in responsive patients.