How to transition a patient with bipolar II disorder and history of antidepressant-induced psychosis, currently taking Emsam (selegiline) 12 mg/d, Aripiprazole 15 mg/d, and Quetiapine 150 mg/d, to Lamotrigine and Lithium?

Transitioning from Emsam, Aripiprazole, and Quetiapine to Lamotrigine and Lithium in Bipolar II Disorder

Direct Recommendation

For a patient with bipolar II disorder and history of antidepressant-induced psychosis, transition by first establishing therapeutic lithium levels (0.8-1.2 mEq/L) while maintaining current medications, then begin lamotrigine titration using the mandatory slow-titration protocol, followed by gradual cross-taper of Emsam (over 2-4 weeks), aripiprazole (reduce by 25-50% every 1-2 weeks), and finally quetiapine (taper over 2-4 weeks) only after lamotrigine reaches 200mg daily. 1, 2, 3

Evidence-Based Rationale for This Transition

Why Lamotrigine and Lithium Are Superior Choices

• Lithium has the strongest evidence base for bipolar disorder, with superior long-term efficacy for preventing both manic and depressive episodes, and uniquely reduces suicide attempts 8.6-fold and completed suicides 9-fold independent of mood-stabilizing effects 1, 2, 3

• Lamotrigine is FDA-approved for maintenance therapy in bipolar disorder and is particularly effective for preventing depressive episodes, which constitute approximately 75% of symptomatic time in bipolar II disorder 1, 3, 4

• The combination of lithium and lamotrigine has compelling evidence for treatment-resistant bipolar depression, making this an optimal evidence-based regimen for bipolar II disorder 5

Addressing the History of Antidepressant-Induced Psychosis

• Emsam (selegiline) is a monoamine oxidase inhibitor antidepressant that carries significant risk of mood destabilization and mania induction in bipolar disorder, and antidepressant monotherapy or inappropriate combination is explicitly contraindicated 1

• The patient's history of antidepressant-induced psychosis makes the transition away from Emsam particularly important, as this represents treatment-emergent mania that requires active pharmacological intervention 1

Step-by-Step Transition Protocol

Phase 1: Establish Lithium Foundation (Weeks 1-3)

Initiate lithium immediately while maintaining all current medications to prevent destabilization during transition 1, 2

• Baseline laboratory assessment required before starting lithium: complete blood count, thyroid function tests (TSH, free T4), urinalysis, BUN, creatinine, serum calcium, and pregnancy test in females 1, 2

• Starting dose: 300mg three times daily (900mg/day total) for patients ≥30kg, or 300mg twice daily (600mg/day) for patients <30kg 1

• Target therapeutic level: 0.8-1.2 mEq/L for acute treatment, though some patients respond at lower concentrations 1, 2

• Check lithium level after 5 days at steady-state dosing, then adjust dose to achieve therapeutic range 1

• Critical safety education: Instruct patient and family on early signs of lithium toxicity (fine tremor, nausea, diarrhea) and to seek immediate medical attention if coarse tremor, confusion, or ataxia develop 1

Phase 2: Begin Lamotrigine Titration (Weeks 2-8)

Start lamotrigine only after lithium reaches therapeutic levels to ensure mood stabilization before adding another agent 1

• Mandatory slow titration to minimize Stevens-Johnson syndrome risk - this is the most critical safety consideration and cannot be rushed 1

• Titration schedule:

  • Weeks 1-2: 25mg daily
  • Weeks 3-4: 50mg daily
  • Weeks 5-6: 100mg daily
  • Weeks 7-8: 200mg daily (target maintenance dose) 1

• If lamotrigine is discontinued for >5 days, restart with full titration schedule rather than resuming previous dose 1

• Monitor weekly for any signs of rash, particularly during first 8 weeks of titration, and discontinue immediately if rash develops 1

Phase 3: Taper Emsam (Weeks 6-10)

Begin tapering Emsam only after lamotrigine reaches at least 100mg daily (approximately week 6 of lamotrigine titration) 1

• Taper Emsam gradually over 2-4 weeks to minimize withdrawal symptoms and rebound depression 1

• Suggested taper schedule for Emsam 12mg/day:

  • Week 1: Reduce to 9mg/day
  • Week 2: Reduce to 6mg/day
  • Week 3: Reduce to 3mg/day
  • Week 4: Discontinue 1

• Monitor closely for worsening depression, suicidal ideation, or mood destabilization during Emsam taper, with weekly visits recommended 1

Phase 4: Reduce Aripiprazole (Weeks 8-12)

Begin reducing aripiprazole only after lamotrigine reaches 200mg daily and Emsam is fully discontinued 1

• Reduce aripiprazole by 25-50% initially (e.g., from 15mg to 7.5-10mg) rather than complete discontinuation 1

• Taper schedule:

  • Weeks 1-2: Reduce to 10mg daily
  • Weeks 2-4: Reduce to 5mg daily
  • Week 4+: Consider discontinuation if patient remains stable 1

• Aripiprazole may be maintained at low dose (5mg) long-term if patient has history of psychotic features or severe mania, as combination therapy with mood stabilizer plus atypical antipsychotic provides superior efficacy for preventing relapse 1, 6, 7

Phase 5: Taper Quetiapine (Weeks 10-14)

Taper quetiapine last, as it provides anxiolytic and sleep benefits that help maintain stability during other medication changes 1, 8

• Taper quetiapine gradually over 2-4 weeks to avoid withdrawal symptoms (insomnia, nausea, agitation) 1

• Suggested taper schedule for quetiapine 150mg/day:

  • Week 1: Reduce to 100mg at bedtime
  • Week 2: Reduce to 50mg at bedtime
  • Week 3: Reduce to 25mg at bedtime
  • Week 4: Discontinue 1

• Alternative approach: Consider maintaining quetiapine 25-50mg at bedtime for sleep if insomnia persists, as quetiapine has compelling evidence for efficacy in bipolar II depression 4, 5

Critical Monitoring Requirements

Lithium Monitoring Schedule

• Lithium levels: Check after 5 days at steady-state dosing, then every 3-6 months once stable 1, 2

• Renal function (BUN, creatinine) and thyroid function (TSH): Every 3-6 months 1, 2

• Urinalysis: Every 3-6 months 1, 2

Clinical Monitoring

• Weekly visits during active medication changes (Phases 1-5) to assess mood symptoms, suicidal ideation, medication adherence, and adverse effects 1

• Monthly visits once stable on lithium and lamotrigine maintenance therapy 1

• Assess for signs of mood destabilization: worsening depression, emergence of hypomanic symptoms, increased anxiety, or behavioral changes at every visit 1

Common Pitfalls to Avoid

Never Rush Lamotrigine Titration

• Rapid-loading lamotrigine dramatically increases risk of Stevens-Johnson syndrome, which can be fatal - the slow titration schedule is mandatory and cannot be accelerated 1

Never Discontinue Multiple Medications Simultaneously

• Tapering multiple medications at once increases risk of acute destabilization and makes it impossible to identify which medication change caused problems 1

• The sequential approach outlined above (lithium first, then lamotrigine, then Emsam, then aripiprazole, then quetiapine) minimizes destabilization risk 1

Never Discontinue Mood Stabilizers Abruptly

• Abrupt lithium discontinuation causes rebound mania in >90% of patients, compared to 37.5% with gradual taper and maintained adherence 1, 2

• Withdrawal of maintenance therapy dramatically increases relapse risk, especially within 6 months following discontinuation 1, 2

Secure Lithium Storage in Patients with Psychiatric History

• Lithium overdoses can be lethal - parents/caregivers must secure medication and remove access to lethal quantities 1

• Prescribe limited quantities with frequent refills to minimize stockpiling risk, particularly given this patient's psychiatric complexity 1

Expected Timeline and Maintenance

Total Transition Duration

• Expect 12-16 weeks for complete transition from current regimen to lithium and lamotrigine maintenance therapy 1

• This timeline prioritizes safety over speed - rushing the transition increases risk of Stevens-Johnson syndrome, mood destabilization, and treatment failure 1

Long-Term Maintenance

• Continue lithium and lamotrigine for at least 12-24 months after achieving mood stabilization 1, 2, 3

• Some patients require lifelong treatment, particularly those with multiple severe episodes, rapid cycling, or history of treatment-resistant symptoms 1, 2

• Maintenance lithium levels: 0.6-1.0 mEq/L (lower than acute treatment range of 0.8-1.2 mEq/L) 1, 2

Adjunctive Psychosocial Interventions

• Psychoeducation should accompany all pharmacotherapy regarding symptoms, course of illness, treatment options, and critical importance of medication adherence 1, 3

• Cognitive-behavioral therapy has strong evidence for both depressive and anxiety components of bipolar disorder and should be implemented alongside medication management 1, 8

• Family-focused therapy helps with medication supervision, early warning sign identification, and reducing access to lethal means 1

Alternative Considerations if Transition Fails

If Patient Cannot Tolerate Lithium

• Consider valproate (divalproex) as alternative mood stabilizer, with target therapeutic range of 50-100 μg/mL, though lithium has superior evidence for suicide prevention 1, 3

• Baseline labs for valproate: liver function tests, complete blood count with platelets, pregnancy test in females 1

If Depressive Symptoms Persist on Lithium-Lamotrigine

• The combination of lithium and lamotrigine has strong evidence for treatment-resistant bipolar depression - ensure adequate trial (8-12 weeks at therapeutic doses) before concluding failure 5

• Consider maintaining low-dose quetiapine (25-50mg at bedtime) as adjunctive therapy, given its compelling evidence for bipolar II depression 4, 5

• If adding antidepressant becomes necessary, prefer SSRIs (sertraline, escitalopram) or bupropion over tricyclics, and always combine with mood stabilizers to prevent mood destabilization 1, 5