What is the best course of treatment for a patient with bipolar II disorder and a history of antidepressant-induced psychosis who is responding well to Emsam (selegiline) 12 mg/d?

Continuation of Emsam 12 mg/d in Bipolar II with History of Antidepressant-Induced Psychosis

Continue Emsam 12 mg/d as monotherapy given the robust clinical response, while maintaining vigilant monitoring for mood destabilization, as this represents successful treatment of a complex case where antidepressant risks have already manifested but the patient has found a tolerable and effective agent. 1

Rationale for Continuation

Why Emsam is Appropriate in This Context

• Selegiline (Emsam) at 12 mg/d maintains MAO-B selectivity at the recommended dose of 10 mg/d, though selectivity diminishes with increasing doses, and the precise dose at which it becomes non-selective may be in the range of 30-40 mg/d 1

• The patient's robust response outweighs theoretical concerns, as bipolar II depression is the prominent feature requiring treatment and represents approximately 75% of symptomatic time in bipolar disorder 2

• Bipolar II patients may have lower switch rates to hypomania compared to bipolar I patients, particularly with certain antidepressant classes, making continued antidepressant therapy more feasible in this population 3

Critical Distinction from Standard Antidepressant Risks

• The history of antidepressant-induced psychosis is concerning, but the current robust success without recurrence of psychotic symptoms suggests Emsam may have a different risk profile for this individual patient 4

• Psychotic symptoms in bipolar II disorder occur in 3-45% of patients and are associated with more hospitalizations and melancholic/catatonic features, making successful treatment without psychosis particularly valuable 4

Mandatory Monitoring Protocol

Mood Destabilization Surveillance

• Assess for hypomanic symptoms every 1-2 weeks initially, then monthly once stable, specifically monitoring for: decreased need for sleep, increased goal-directed activity, racing thoughts, increased talking, and risky behavior 5

• Monitor for mixed depression features (concurrent subsyndromal hypomanic symptoms during depression), as antidepressants may worsen intradepression hypomanic symptoms 6

• Watch for rapid cycling patterns (≥4 mood episodes per year), as this subtype is extensively associated with antidepressant-induced switch phenomena and would necessitate treatment modification 3

Psychosis Monitoring

• Evaluate for any re-emergence of psychotic symptoms at each visit, as the patient's history of antidepressant-induced psychosis represents a significant risk factor 4

• Assess for perceptual disturbances, paranoid ideation, or disorganized thinking that could signal early psychotic decompensation 5

Dietary and Drug Interaction Precautions

Tyramine Restrictions at 12 mg/d

• Rare cases of hypertensive reactions associated with tyramine-containing foods have been reported even at the recommended 10 mg/d dose, so counsel the patient to avoid aged cheeses, cured meats, fermented foods, and excessive amounts of caffeine 1

• The selectivity for MAO-B is further diminished with increasing daily doses, making dietary precautions increasingly important at 12 mg/d compared to lower doses 1

Contraindicated Medication Combinations

• Absolutely avoid combining Emsam with SSRIs (fluoxetine, sertraline, paroxetine), SNRIs, or tricyclic antidepressants, as serious and sometimes fatal reactions with hyperthermia, rigidity, autonomic instability, and mental status changes have been reported 1

• At least 14 days must elapse between discontinuation of Emsam and initiation of any tricyclic antidepressant or SSRI; for fluoxetine specifically, at least 5 weeks must elapse due to its long half-life 1

• Severe CNS toxicity with hyperpyrexia and death have been reported with combinations of MAOIs and tricyclic antidepressants 1

When to Consider Mood Stabilizer Addition

Indications for Augmentation

• If any hypomanic symptoms emerge (even if associated with improved functioning), add a mood stabilizer such as lithium or valproate, as hypomania should be treated because depression often follows the hypomania-depression cycle 6

• Lithium is supported by multiple controlled studies as the only preventive treatment for both depression and hypomania with established efficacy 6, 2

• Lamotrigine has shown efficacy in delaying depression recurrences and is recommended as a first-line mood stabilizer, though it requires slow titration (starting 25 mg daily, increasing by 25-50 mg every 1-2 weeks) to minimize Stevens-Johnson syndrome risk 7, 2

Alternative Atypical Antipsychotic Options

• If psychotic symptoms re-emerge or mood destabilization occurs, consider adding quetiapine, aripiprazole, lurasidone, or cariprazine, which are recommended first-line agents for bipolar disorder 7, 2

• Lurasidone demonstrates efficacy for bipolar depression with minimal weight gain and less sedation than other antipsychotics, making it particularly suitable if augmentation becomes necessary 7

Common Pitfalls to Avoid

• Do not discontinue Emsam abruptly if problems arise; taper gradually while introducing alternative treatment to prevent depressive relapse 5

• Do not assume that absence of hypomania means the patient has unipolar depression; bipolar II is underdiagnosed with a lifetime community prevalence of approximately 5% (including bipolar spectrum) versus the 0.5% reported in DSM-IV 6

• Do not add another antidepressant to "boost" response, as this violates MAO inhibitor safety guidelines and dramatically increases risk of serotonin syndrome 1

• Do not neglect psychosocial interventions; cognitive behavioral therapy and psychoeducation should be routinely offered as adjunctive treatment 7