Is a two-week washout period necessary when switching an adult patient with depression or bipolar disorder from Emsam (selegiline) 12 mg/day to lamotrigine 200 mg?

Switching from Emsam to Lamotrigine: Washout Requirements

A two-week washout period is absolutely necessary when switching from Emsam (selegiline) 12 mg/day to lamotrigine 200 mg, as mandated by FDA labeling to prevent potentially fatal drug interactions. 1

Critical Safety Rationale

FDA-Mandated Washout Period

• At least 14 days must elapse between discontinuation of selegiline and initiation of any subsequent psychotropic medication, as explicitly stated in the FDA drug label for selegiline 1
• This washout period is required because selegiline at 12 mg/day (above the 10 mg/day threshold) loses its MAO-B selectivity and functions as a non-selective MAO inhibitor, creating risk for severe CNS toxicity, hyperpyrexia, and death when combined with other psychotropic agents 1
• The FDA label documents severe CNS toxicity associated with hyperpyrexia and death when MAO inhibitors are combined with various psychotropic medications, including cases of hypertension, syncope, asystole, diaphoresis, seizures, changes in behavioral and mental status, and muscular rigidity 1

Why This Specific Switch Requires Caution

• Selegiline at 12 mg/day exceeds the recommended 10 mg/day dose where MAO-B selectivity is maintained, placing it in the range where non-selective MAO inhibition occurs (selectivity is lost somewhere between 30-40 mg/day, but diminishes progressively above 10 mg/day) 1
• Although lamotrigine is not a serotonergic agent and works through sodium and calcium channel inhibition rather than monoamine modulation, the FDA mandates a 14-day washout after discontinuing selegiline before starting any tricyclic antidepressant or other psychotropic medication 1
• The mechanisms of MAO inhibitor interactions are not fully understood, making it prudent to follow the conservative 14-day washout guideline even for non-serotonergic agents like lamotrigine 1

Practical Implementation Algorithm

Step 1: Discontinue Emsam

• Stop Emsam 12 mg/day immediately
• Counsel patient on maintaining a low-tyramine diet for the full 14-day washout period, as MAO inhibition persists after drug discontinuation 1

Step 2: Monitor During Washout

• Monitor for hypertensive crisis symptoms during the 14-day washout period, particularly if dietary tyramine is consumed 1
• Assess for worsening mood symptoms during the medication-free interval
• Monitor suicidal ideation intensively, as medication transitions increase risk 2

Step 3: Initiate Lamotrigine After 14 Days

• Begin lamotrigine only after the complete 14-day washout period has elapsed 1
• Use slow titration over 6 weeks to reach the target dose of 200 mg/day to minimize risk of serious rash (incidence 0.1%, including Stevens-Johnson syndrome) 3, 4
• Standard titration: weeks 1-2 at 25 mg/day, weeks 3-4 at 50 mg/day, week 5 at 100 mg/day, week 6 at 200 mg/day 3, 4

Common Pitfalls to Avoid

• Never abbreviate or eliminate the 14-day washout period, even if the patient's clinical condition is deteriorating, as the risk of fatal CNS toxicity outweighs the benefits of rapid medication transition 1
• Do not assume lamotrigine is safe to start earlier simply because it lacks serotonergic activity—the FDA mandates the 14-day washout for all psychotropic medications after selegiline discontinuation 1
• If the patient cannot tolerate a 14-day medication-free period due to severe mood instability, consider hospitalization for close monitoring rather than violating the washout requirement 1