How should a patient with bipolar I disorder and predominant depressive polarity, currently stabilized on Emsam (selegiline) 12 mg/24 hr transdermal patch, aripiprazole 15 mg, and quetiapine 150 mg, be transitioned to lamotrigine and lithium?

Transitioning from Emsam-Aripiprazole-Quetiapine to Lamotrigine-Lithium in Bipolar I Disorder with Predominant Depressive Polarity

Critical Safety Consideration: MAOI Washout Period

This transition requires a mandatory 14-day washout period after discontinuing Emsam (selegiline) before initiating lithium or any other serotonergic agents, due to the risk of hypertensive crisis and serotonergic interactions. During this washout period, the patient will need bridging therapy to maintain mood stability.

Recommended Cross-Titration Algorithm

Phase 1: Discontinue Emsam and Begin Bridging (Days 1-14)

• Day 1: Remove the Emsam 12 mg/24 hr patch and do not reapply 1
• Days 1-14: Continue aripiprazole 15 mg and quetiapine 150 mg unchanged as bridging therapy to prevent mood destabilization during the MAOI washout period 1
• Days 1-14: Maintain dietary MAOI restrictions (avoid tyramine-rich foods) throughout the entire washout period, as selegiline's MAOI effects persist for 14 days after discontinuation

Phase 2: Initiate Lithium (Days 15-21)

• Day 15: Obtain baseline laboratory studies before starting lithium: complete blood count, thyroid function tests (TSH, free T4), urinalysis, blood urea nitrogen, creatinine, serum calcium, and pregnancy test in females 1
• Day 15: Start lithium 300 mg three times daily (900 mg/day total) if patient weighs ≥30 kg, or 300 mg twice daily (600 mg/day) if <30 kg 1
• Day 20: Check lithium level after 5 days at steady-state dosing, targeting 0.8-1.2 mEq/L for acute treatment 1
• Days 15-21: Continue aripiprazole 15 mg and quetiapine 150 mg unchanged 1

Phase 3: Initiate Lamotrigine with Slow Titration (Weeks 3-8)

Critical: Lamotrigine must be titrated slowly over 6-8 weeks to minimize the risk of Stevens-Johnson syndrome and serious rash, which occurs in 0.1% of adults 2, 3, 4.

• Weeks 3-4 (Days 15-28): Lamotrigine 25 mg once daily 2, 3, 4
• Weeks 5-6 (Days 29-42): Lamotrigine 50 mg once daily 2, 3, 4
• Week 7 (Days 43-49): Lamotrigine 100 mg once daily 2, 3, 4
• Week 8 onwards (Day 50+): Lamotrigine 200 mg once daily (standard target dose) 2, 3, 4
• Throughout Weeks 3-8: Continue lithium at therapeutic dose (0.8-1.2 mEq/L), aripiprazole 15 mg, and quetiapine 150 mg 1

Phase 4: Taper Aripiprazole (Weeks 9-11)

• Week 9: Once lamotrigine reaches 200 mg daily and lithium levels are therapeutic, begin reducing aripiprazole from 15 mg to 10 mg daily 1
• Week 10: Reduce aripiprazole from 10 mg to 5 mg daily 1
• Week 11: Discontinue aripiprazole completely 1
• Throughout Weeks 9-11: Continue lithium at therapeutic dose, lamotrigine 200 mg, and quetiapine 150 mg 1

Phase 5: Taper Quetiapine (Weeks 12-14)

• Week 12: Reduce quetiapine from 150 mg to 100 mg at bedtime 1
• Week 13: Reduce quetiapine from 100 mg to 50 mg at bedtime 1
• Week 14: Discontinue quetiapine completely 1
• Final regimen: Lithium (therapeutic level 0.8-1.2 mEq/L for acute treatment, then 0.6-1.0 mEq/L for maintenance) plus lamotrigine 200 mg daily 1, 2, 3, 4

Critical Monitoring Requirements

Weekly Monitoring During Lamotrigine Titration (Weeks 3-8)

• Assess for rash at every visit: Any rash requires immediate evaluation and potential discontinuation of lamotrigine 2, 3, 4
• Monitor mood symptoms: Assess for worsening depression, emergence of manic symptoms, or suicidal ideation 1
• Verify medication adherence: Non-compliance dramatically increases relapse risk (>90% vs 37.5% in compliant patients) 1

Lithium Monitoring Schedule

• Week 3 (Day 20): First lithium level after 5 days at steady-state dosing 1
• Adjust lithium dose based on level: Target 0.8-1.2 mEq/L for acute treatment 1
• Ongoing monitoring: Lithium levels, renal function (BUN, creatinine), thyroid function (TSH), and urinalysis every 3-6 months once stable 1

Metabolic Monitoring for Quetiapine (Until Discontinued)

• Baseline (if not recently done): Body mass index, waist circumference, blood pressure, fasting glucose, fasting lipid panel 1
• Monthly: BMI monitoring while on quetiapine 1

Important Clinical Considerations

Rationale for This Specific Transition Strategy

• Lamotrigine is particularly effective for preventing depressive episodes in bipolar I disorder with predominant depressive polarity, significantly delaying time to intervention for depression compared to placebo 2, 3, 4
• Lithium provides antimanic coverage and has unique anti-suicide effects, reducing suicide attempts 8.6-fold and completed suicides 9-fold, independent of mood-stabilizing properties 1
• The combination of lamotrigine plus lithium addresses both depressive and manic poles, as lamotrigine shows limited efficacy for mania prevention while lithium is superior for preventing manic episodes 3, 4

Common Pitfalls to Avoid

• Never rapid-load lamotrigine: This dramatically increases the risk of Stevens-Johnson syndrome, which can be fatal 1
• Never discontinue Emsam and start lithium simultaneously: The 14-day MAOI washout is mandatory to prevent hypertensive crisis and serotonergic interactions
• Do not taper aripiprazole or quetiapine before lamotrigine reaches therapeutic dose (200 mg): Premature discontinuation of antipsychotics increases risk of mood destabilization 1
• If lamotrigine is interrupted for >5 days during titration, restart with the full titration schedule rather than resuming the previous dose to minimize rash risk 1

Alternative Considerations if Transition Fails

• If depressive symptoms worsen during the transition: Consider temporarily increasing quetiapine dose or delaying its taper until lamotrigine reaches full therapeutic effect (typically 8-12 weeks at 200 mg) 3, 4
• If manic symptoms emerge: Ensure lithium levels are therapeutic (0.8-1.2 mEq/L) and consider maintaining aripiprazole longer or increasing lithium dose 1
• If insomnia persists after quetiapine discontinuation: Consider non-pharmacological interventions (cognitive behavioral therapy for insomnia) or low-dose trazodone as an alternative to quetiapine 1

Maintenance Therapy Duration

• Continue the lamotrigine-lithium combination for at least 12-24 months after achieving mood stabilization 1
• Some patients with predominant depressive polarity may require lifelong treatment, particularly those with multiple severe episodes or history of rapid cycling 1
• Withdrawal of lithium is associated with dramatically increased relapse risk (>90% in non-compliant patients), especially within 6 months of discontinuation 1

Psychosocial Interventions

• Combine pharmacotherapy with psychoeducation about bipolar disorder symptoms, course of illness, treatment options, and critical importance of medication adherence 1
• Cognitive-behavioral therapy has strong evidence for addressing depressive components of bipolar disorder and should be offered as adjunctive treatment 1