Emsam (Selegiline Transdermal System) Treatment Protocol for Major Depressive Disorder
Recommended Dosing Strategy
Start Emsam at 6 mg/24 hours applied once daily as the initial dose for major depressive disorder, which is effective and does not require dietary tyramine restrictions at this dose. 1, 2, 3
Dose Titration
- Initial dose: 6 mg/24 hours patch applied once daily 1, 4, 3
- Dose escalation: May increase to 9 mg/24 hours or 12 mg/24 hours if inadequate response after 6-8 weeks, though dietary tyramine restrictions become necessary at these higher doses 5, 2, 4
- The 6 mg/24 hours dose provides sufficient brain MAO inhibition for antidepressant effects while avoiding significant gastrointestinal MAO-A inhibition, eliminating the "cheese reaction" risk 1, 3
Critical Dietary Restrictions
At 6 mg/24 hours, no dietary tyramine restrictions are required. 1, 2, 3
At 9 mg/24 hours or 12 mg/24 hours, dietary tyramine restriction is mandatory to prevent hypertensive crisis, though current data on this requirement remains insufficient 5, 2
Monitoring Protocol
Begin monitoring within 1-2 weeks of initiation, focusing on suicidal ideation, agitation, irritability, and unusual behavioral changes. 6
- Monitor for treatment response using validated tools (PHQ-9 or HAM-D) at regular intervals 6, 7
- Assess for adequate response at 6-8 weeks; if inadequate, modify treatment 6
- The acute treatment phase lasts 6-12 weeks 6, 7
Treatment Duration
Continue treatment for 4-9 months after achieving satisfactory response in first-episode depression. 6
For patients with 2 or more depressive episodes, consider years to lifelong maintenance therapy. 6
- A 52-week prevention study demonstrated significant benefits for continuation treatment 2
Absolute Contraindications and Drug Interactions
Do not combine Emsam with the following medications due to risk of severe CNS toxicity, serotonin syndrome, or death: 5, 2
- Selective serotonin reuptake inhibitors (SSRIs): fluoxetine, sertraline, paroxetine 5
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) 2
- Tricyclic antidepressants: amitriptyline, protriptyline - severe CNS toxicity with hyperpyrexia and death reported 5
- Meperidine and multiple analgesics 2
- Carbamazepine (significantly increases selegiline levels) 2
- Indirect sympathomimetics 2
Washout Periods
When discontinuing contraindicated medications before starting Emsam: Wait 1 week (4-5 half-lives) for most medications 2
When discontinuing fluoxetine before starting Emsam: Wait at least 5 weeks due to long half-life of fluoxetine and its active metabolite 5
When discontinuing Emsam before starting contraindicated medications: Wait 2 weeks 2
When discontinuing Emsam before starting tricyclic antidepressants or SSRIs: Wait at least 14 days 5
Common Adverse Effects
The most frequently reported side effects include 2, 4:
- Application site reactions (most common) 2
- Insomnia 2
- Orthostatic hypotension (slightly higher rate than placebo) 2
- Notably absent: No significant weight gain or sexual dysfunction 2
Safety Profile
No cases of hypertensive crisis were reported in clinical trials at any dose (6,9, or 12 mg/24 hours), even without dietary restrictions. 2, 3
Tyramine challenge studies demonstrated a comfortable safety margin at 6 mg/24 hours 2
Optimal Patient Selection
Emsam is particularly appropriate for patients who 1, 8:
- Cannot tolerate oral antidepressants
- Have poor medication adherence
- Present with atypical depressive symptoms
- Have failed other antidepressants
- Have anxious depression 8
- Have swallowing difficulties 8
Clinical Pitfalls to Avoid
Never exceed 10 mg/day without dietary restrictions - selectivity for MAO-B diminishes with increasing doses, and non-selective MAO inhibition occurs around 30-40 mg/day 5
Do not assume all doses are dietary restriction-free - only the 6 mg/24 hours dose has established safety without tyramine restrictions 1, 2
Do not overlook the washout period requirements - inadequate washout periods before or after Emsam can result in fatal serotonin syndrome or hypertensive crisis 5, 2