What is the recommended washout period for a patient with bipolar II disorder taking Emsam (selegiline) 9 mg/day before initiating another antidepressant?

Washout Period for Emsam 9 mg/day in Bipolar II Disorder

Direct Recommendation

At least 14 days should elapse between discontinuation of Emsam (selegiline transdermal) 9 mg/day and initiation of treatment with another antidepressant, particularly tricyclic antidepressants or selective serotonin reuptake inhibitors. 1

Evidence-Based Rationale

The FDA-approved prescribing information for selegiline explicitly states that at least 14 days must pass between stopping selegiline and starting tricyclic antidepressants or SSRIs 1. This washout period is critical because:

• Severe CNS toxicity associated with hyperpyrexia and death have been reported when combining selegiline with tricyclic antidepressants, with documented cases showing tremors, agitation, restlessness, unresponsiveness, and death 1

• Serious, sometimes fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with rapid vital sign fluctuations, and mental status changes progressing to delirium and coma have been reported when combining selegiline with SSRIs (fluoxetine, sertraline, paroxetine) 1

• At the 9 mg/day dose, selegiline's selectivity for MAO-B is already diminished compared to the 6 mg dose, increasing the risk of non-selective MAO inhibition and associated drug interactions 1

Special Consideration for Fluoxetine

If the patient was previously taking fluoxetine, at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of Emsam. 1 This extended period is necessary due to fluoxetine's long half-life and its active metabolite.

Clinical Context for Bipolar II Disorder

For patients with bipolar II disorder specifically:

• Bipolar II depression is the predominant feature of the illness, with depressive episodes outnumbering hypomanic episodes by a ratio of 39:1, making antidepressant transitions common 2

• The condition is frequently misdiagnosed as major depressive disorder and inappropriately treated with antidepressant monotherapy, which may worsen prognosis 2

• When transitioning from Emsam to another treatment, mood stabilizers (lithium, lamotrigine, valproate) or atypical antipsychotics should be considered as alternatives to antidepressant monotherapy 3, 4, 5

• Antidepressant monotherapy is contraindicated in bipolar disorder due to risk of mood destabilization, mania induction, and rapid cycling 6

Critical Safety Algorithm

1. Day 0: Discontinue Emsam 9 mg/day completely
2. Days 1-14: Washout period with no MAOIs, tricyclics, or SSRIs
3. Day 14 or later: Earliest safe initiation of tricyclic antidepressants or SSRIs
4. Exception for fluoxetine: If fluoxetine is the planned next medication, wait minimum 14 days; if transitioning FROM fluoxetine TO Emsam, wait minimum 5 weeks 1

Common Pitfalls to Avoid

• Never overlap Emsam with SSRIs or tricyclics - the mechanisms of serotonin syndrome are not fully understood, and fatal reactions have occurred even at the recommended 10 mg/day dose of selegiline 1

• Do not assume the 6 mg dietary restrictions apply to 9 mg - at 9 mg/day, selegiline's selectivity for MAO-B is further diminished, and rare hypertensive reactions with tyramine-containing foods have been reported even at the recommended 10 mg/day dose 1

• Avoid shortening the washout period - the 14-day minimum is based on the time needed for MAO enzyme regeneration and is not negotiable for patient safety 1

• Consider mood stabilizer monotherapy instead - given the bipolar II diagnosis, transitioning to lithium, lamotrigine, or quetiapine may be more appropriate than another antidepressant, as these have demonstrated efficacy in preventing mood episode relapse in bipolar II disorder 3, 4, 5