EMSAM (selegiline transdermal system) is a monoamine oxidase inhibitor (MAOI) antidepressant delivered through a transdermal patch, offering a novel mechanism of action for patients who have not achieved adequate response with other antidepressant therapies. It represents a significant advancement in the management of major depressive disorder (MDD), particularly in cases where oral antidepressants have proven ineffective or intolerable. By utilizing a transdermal delivery system, EMSAM bypasses first-pass metabolism, allowing for targeted neurotransmitter modulation with a potentially improved side effect profile compared to traditional oral MAOIs. This delivery method also permits effective antidepressant dosing while mitigating the need for strict dietary tyramine restrictions at the lowest dosage strength, enhancing both safety and patient quality of life.

Features

• Active Ingredient: Selegiline, a selective monoamine oxidase-B (MAO-B) inhibitor at lower doses, with broader MAO-A and MAO-B inhibition at antidepressant doses.
• Delivery System: Transdermal patch providing continuous 24-hour delivery of medication through the skin.
• Available Strengths: 6 mg/24 hr, 9 mg/24 hr, and 12 mg/24 hr patch sizes.
• Dosing Regimen: Once-daily application, with each patch worn for 24 hours.
• Pharmacokinetics: Steady-state plasma concentrations achieved within 2-3 days of initiation.
• Mechanism of Action: Increases concentrations of monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) in the central nervous system through irreversible inhibition of monoamine oxidase enzymes.

Benefits

• Effective for treatment-resistant depression with a mechanism of action distinct from SSRIs, SNRIs, and other common antidepressant classes
• Transdermal delivery minimizes gastrointestinal side effects commonly associated with oral antidepressants
• Lower dietary restrictions at the 6 mg/24 hr dosage compared to oral MAOIs
• Once-daily dosing improves adherence compared to multiple-daily dosing regimens
• Stable drug delivery maintains consistent plasma levels, reducing peak-trough fluctuations
• May improve anhedonia and fatigue through dopaminergic activity

Common use

EMSAM is 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 medications, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and other first-line treatments. The transdermal delivery system makes it suitable for patients who experience significant gastrointestinal side effects with oral antidepressants or those with compliance issues related to multiple daily dosing. Clinical studies have demonstrated efficacy in reducing depressive symptoms as measured by standardized rating scales, with significant separation from placebo observed in multiple randomized controlled trials.

Dosage and direction

Initial Dose: Therapy should be initiated with the 6 mg/24 hr patch applied once daily. Dose Titration: If inadequate response is observed after 2-4 weeks, the dose may be increased to 9 mg/24 hr, and subsequently to 12 mg/24 hr if needed, with at least 2-week intervals between dose adjustments. Application Instructions:

• Apply to dry, intact skin on the upper torso (below the neck and above the waist), upper thigh, or outer surface of the upper arm
• Rotate application sites with each new patch to prevent skin irritation
• Avoid applying to oily, hairy, irritated, broken, or calloused skin
• Press patch firmly in place for at least 10 seconds to ensure adhesion
• Remove the previous patch before applying a new one
• Wash hands thoroughly after application or handling Duration: Each patch is designed to be worn for 24 hours and then replaced.

Precautions

• Hypertensive Crisis Risk: Although the transdermal delivery reduces this risk, patients should be educated about the potential for hypertensive reactions, particularly at higher doses (9 mg/24 hr and 12 mg/24 hr)
• Serotonin Syndrome: Monitor for symptoms when used concomitantly with other serotonergic drugs
• Application Site Reactions: Rotate sites and monitor for significant dermatitis; most reactions are mild to moderate and resolve without treatment
• Orthostatic Hypotension: May occur, particularly during dose titration
• Activation of Mania/Hypomania: Monitor patients with bipolar disorder for symptom emergence
• Cognitive Impairment: Use caution when operating machinery until response is known
• Pregnancy and Lactation: Use only if potential benefit justifies potential risk to fetus or infant

Contraindications

• Concomitant use with other MAOIs
• Concomitant use with sympathomimetic amines (including amphetamines, cold products containing pseudoephedrine or phenylephrine)
• Concomitant use with meperidine, tramadol, methadone, propoxyphene, or other opioids (except under careful observation)
• Concomitant use with dextromethorphan
• Concomitant use with St. John’s wort, cyclobenzaprine, or other serotonergic agents
• Pheochromocytoma
• History of hypersensitivity to selegiline or any component of the transdermal system
• Children under 12 years of age

Possible side effects

Common (≥5% and greater than placebo):

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

Less common but clinically significant:

• Orthostatic hypotension
• Sexual dysfunction
• Weight changes
• Serotonin syndrome (especially with concomitant serotonergic agents)
• Hypertensive crisis (particularly with tyramine-containing foods at higher doses)
• Activation of mania/hypomania in susceptible patients

Drug interaction

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

• Serotonergic agents: SSRIs, SNRIs, tricyclic antidepressants, triptans, buspirone, lithium - risk of serotonin syndrome
• Sympathomimetics: Amphetamines, methylphenidate, ephedrine, pseudoephedrine - may precipitate hypertensive crisis
• Opioids: Particularly meperidine, tramadol, methadone - risk of serotonin syndrome or exaggerated opioid effects
• Dextromethorphan: Risk of serotonin syndrome or psychotic behavior
• Tyramine-rich foods: Significant interaction at doses above 6 mg/24 hr, requiring dietary restrictions
• Other MAOIs: Absolute contraindication due to exaggerated MAOI effects
• Carbamazepine, oxcarbazepine: May reduce selegiline concentrations
• Bupropion: Theoretical increased risk of hypertension

Missed dose

If a dose is missed, the patient should apply the patch as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not apply extra patches to make up for a missed dose. Doubling the dose may increase the risk of adverse effects, including hypertensive crisis. If multiple doses are missed, consultation with a healthcare provider is recommended before resuming therapy, as dose re-titration may be necessary.

Overdose

Symptoms of EMSAM overdose may include:

• Severe hypertension (potentially leading to hypertensive crisis)
• Serotonin syndrome (agitation, confusion, tachycardia, hyperthermia, muscle rigidity)
• Drowsiness, dizziness, or lightheadedness
• Seizures
• Coma

Management involves immediate removal of the patch and symptomatic treatment. Hypertension should be managed with rapidly acting antihypertensive agents such as phentolamine or nitroprusside. Serotonin syndrome may require cyproheptadine and supportive care. Patients should be monitored for at least 2 weeks due to the irreversible nature of MAO inhibition. Hospitalization and intensive supportive care are typically necessary for significant overdoses.

Storage

• Store at room temperature (20°C to 25°C/68°F to 77°F)
• Keep in original pouch until time of use
• Protect from moisture and humidity
• Keep out of reach of children and pets
• Do not store in bathroom or other areas with high humidity
• Do not freeze
• Properly dispose of used patches by folding adhesive sides together and discarding 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 medication may vary, and only a healthcare professional can determine the appropriate treatment based on individual medical history, current medications, and specific clinical circumstances. Patients should not initiate, discontinue, or change dosage of EMSAM without consulting their healthcare provider. The complete prescribing information should be consulted before initiating therapy.

Reviews

Clinical trials have demonstrated EMSAM’s efficacy in treating major depressive disorder. In a 6-week double-blind, placebo-controlled trial of 177 outpatients with MDD, the 6 mg/24 hr dose showed statistically significant improvement in MADRS scores compared to placebo (p=0.01). Another 8-week trial involving 265 patients found significant separation from placebo with the 6 mg/24 hr dose on both primary efficacy measures. Long-term extension studies have supported maintenance of effect for up to 12 months. Real-world evidence suggests particular benefit in patients who have failed multiple antidepressant trials, with response rates of 40-50% in treatment-resistant populations. The transdermal delivery system is generally well-tolerated, with application site reactions being the most common adverse effect, typically diminishing over time. Many clinicians report particular success with patients who have experienced significant side effects with oral antidepressants or who present with prominent fatigue and anhedonia symptoms.