What are the guidelines for prescribing Emsam (selegiline) transdermally for major depressive disorder?

Prescribing Emsam (Selegiline Transdermal System) for Major Depressive Disorder

Emsam is FDA-approved for major depressive disorder and offers a unique advantage: at the 6 mg/24 hour dose, no dietary tyramine restrictions are required, making it the only MAOI in the US with this safety profile. 1, 2

Dosing Guidelines

Starting Dose

• Begin with 6 mg/24 hours applied once daily 2, 3
• This is the target therapeutic dose that demonstrated efficacy in controlled trials 3
• At this dose, tyramine dietary restrictions are NOT required 1, 2

Dose Escalation

• If inadequate response after 6-8 weeks, may increase to 9 mg/24 hours or 12 mg/24 hours 1, 3
• Critical caveat: At doses of 9 mg/24 hours or higher, patients MUST follow tyramine-restricted diet 1, 2
• The safety margin without dietary restrictions has only been established for 6 mg/24 hours 4

Application Instructions

• Apply patch to dry, intact skin on upper torso, upper thigh, or outer surface of upper arm 2
• Rotate application sites to minimize skin reactions 4
• Apply once every 24 hours 3

Contraindications and Drug Interactions

Absolute Contraindications

The following medications must be completely discontinued before starting Emsam: 1, 5

• SSRIs and SNRIs: Stop 1 week before Emsam (5 weeks for fluoxetine due to long half-life) 1
• Tricyclic antidepressants: Stop at least 14 days before Emsam 1
• Meperidine and other opioid analgesics: Risk of severe toxicity including stupor, rigidity, agitation, and death 1
• Carbamazepine: Significantly increases selegiline levels 5
• Sympathomimetics (particularly indirect-acting like ephedrine): Risk of hypertensive crisis 1, 5

Washout Periods

• When stopping other antidepressants to start Emsam: Wait 4-5 half-lives (generally 1 week, except fluoxetine which requires 5 weeks) 5
• When stopping Emsam to start other antidepressants: Wait 2 weeks before initiating SSRIs, SNRIs, or tricyclics 1, 5

Monitoring Requirements

Initial Phase (First 1-2 Weeks)

• Monitor closely for suicidal ideation, agitation, irritability, or unusual behavioral changes 6
• Risk of suicide attempts is highest during first 1-2 months of any antidepressant treatment 6
• Assess for application site reactions (most common adverse effect) 4

Ongoing Monitoring

• Evaluate therapeutic response and adverse effects regularly beginning within 1-2 weeks 6
• Monitor blood pressure for orthostatic hypotension (slightly increased risk with Emsam) 5, 4
• Screen for melanoma regularly: Parkinson's disease patients (for whom oral selegiline is used) have 2-6 fold increased melanoma risk; periodic dermatologic examination recommended 1
• Assess for impulse control disorders (pathological gambling, increased sexual urges) - may require dose reduction or discontinuation 1

Treatment Duration

• Continue for 4-9 months after satisfactory response for first episode of MDD 6
• For patients with 2 or more prior episodes: Consider longer-term maintenance therapy (≥1 year) 6
• Long-term efficacy demonstrated in 52-week relapse-prevention trial 3

Modifying Treatment for Inadequate Response

• If no adequate response within 6-8 weeks, modify treatment 6
• Options include dose escalation (with dietary restrictions at higher doses) or switching to alternative antidepressant 6

Advantages Over Oral MAOIs

Emsam's transdermal delivery bypasses hepatic first-pass metabolism, avoiding significant inhibition of gastrointestinal and hepatic MAO-A activity 2, 7

• No hypertensive crises reported in clinical trials at any dose when dietary restrictions followed 4
• Lower incidence of sexual dysfunction compared to SSRIs 3, 4
• Minimal weight gain (similar to placebo) 3, 4
• Avoids swallowing issues with oral medications 7
• May be particularly effective for atypical depression and anxious depression 7

Common Pitfalls to Avoid

• Do not exceed 6 mg/24 hours without implementing tyramine-restricted diet 1, 2
• Do not combine with SSRIs, SNRIs, or tricyclics without appropriate washout periods - risk of serotonin syndrome or severe CNS toxicity 1
• Do not use with meperidine or tramadol - risk of fatal reactions 1, 5
• Application site reactions occur in majority of patients but are usually mild-to-moderate; counsel patients this is expected 4
• Insomnia is dose-related; consider timing of application if problematic 4