What is the recommended dosing schedule for switching a patient from Abilify (aripiprazole) to Rexulti (brexpiprazole), including those on ≥10 mg daily?

Switching from Aripiprazole to Brexpiprazole: Recommended Dosing Schedule

For patients on aripiprazole ≥10 mg daily, initiate brexpiprazole at 1-2 mg daily while simultaneously tapering aripiprazole by 50% in week 1, then discontinue aripiprazole completely in week 2 as brexpiprazole is titrated to target dose of 2-4 mg daily. This gradual cross-titration approach minimizes withdrawal symptoms and maintains therapeutic dopamine receptor coverage during the transition between these pharmacologically similar agents 1, 2, 3.

Evidence-Based Rationale for Cross-Titration Strategy

Both aripiprazole and brexpiprazole are dopamine D2 partial agonists with similar receptor binding profiles, but they differ in their binding affinities and pharmacokinetic properties 4, 5. Aripiprazole has a long elimination half-life of approximately 75 hours (94 hours for its active metabolite dehydroaripiprazole), meaning steady-state concentrations are attained within 14 days and plasma levels persist for weeks after discontinuation 5. This pharmacokinetic profile supports a gradual transition rather than abrupt switching.

Abrupt discontinuation of aripiprazole increases the risk of withdrawal symptoms (anxiety, insomnia, irritability, mood changes) and symptom exacerbation, particularly in patients with schizophrenia or bipolar disorder 1, 2, 3. Research demonstrates that patients switched with immediate discontinuation of their previous antipsychotic showed increased symptom severity at week 1, supporting the superiority of gradual tapering strategies 3.

Specific Switching Protocol by Current Aripiprazole Dose

For Patients on Aripiprazole 10-15 mg Daily:

Week 1:

• Reduce aripiprazole to 5-7.5 mg daily (50% reduction)
• Initiate brexpiprazole 1 mg daily
• Monitor for withdrawal symptoms, akathisia, and symptom exacerbation 1, 2, 6

Week 2:

• Discontinue aripiprazole completely
• Increase brexpiprazole to 2 mg daily
• Continue monitoring for extrapyramidal symptoms and efficacy 1, 2

Week 3-4:

• Titrate brexpiprazole to target dose of 2-4 mg daily based on response and tolerability
• Assess for full therapeutic effect (may require 1-4 weeks to reach full efficacy) 6, 5

For Patients on Aripiprazole ≥20 mg Daily:

Week 1:

• Reduce aripiprazole to 10-15 mg daily (approximately 50% reduction)
• Initiate brexpiprazole 1 mg daily
• Monitor closely for symptom worsening 6, 3

Week 2:

• Reduce aripiprazole to 5 mg daily
• Increase brexpiprazole to 2 mg daily
• Assess tolerability and early response 1, 2

Week 3:

• Discontinue aripiprazole completely
• Maintain brexpiprazole at 2 mg daily or increase to 3 mg if needed
• Monitor for withdrawal symptoms 3

Week 4:

• Titrate brexpiprazole to target dose of 2-4 mg daily based on clinical response
• Full therapeutic effect may not be evident until 2-4 weeks at target dose 5

Critical Monitoring Parameters During Transition

Weeks 1-4 (Acute Transition Phase):

• Monitor weekly for extrapyramidal symptoms (parkinsonism, akathisia, restlessness) as both agents can cause EPS, though brexpiprazole may have lower risk 1, 2, 6
• Assess for withdrawal symptoms: anxiety, insomnia, irritability, agitation, mood changes 1, 2
• Evaluate symptom control using standardized measures (BPRS, CGI-S for schizophrenia; YMRS for bipolar disorder) 3
• Monitor for common brexpiprazole adverse effects: somnolence, akathisia, nausea, weight gain 2, 6

Ongoing Maintenance Monitoring:

• Metabolic parameters (weight, BMI, fasting glucose, lipids) at baseline, 3 months, then annually 7
• Movement disorder assessment (AIMS, SAS, BAS) every 3-6 months 3
• Symptom severity and functional status monthly until stable, then quarterly 6

Alternative Approach: Direct Switch Without Cross-Titration

For patients on low-dose aripiprazole (5 mg daily) or those with urgent need for medication change, a direct switch may be considered: Discontinue aripiprazole and initiate brexpiprazole 1-2 mg daily the following day, with close monitoring for the first 2 weeks 6, 3. However, this approach carries higher risk of early symptom worsening and should be reserved for specific clinical circumstances where gradual cross-titration is not feasible 3.

Common Pitfalls to Avoid

• Never discontinue aripiprazole abruptly when switching to brexpiprazole—the long half-life means plasma levels persist, but sudden cessation increases withdrawal risk and symptom exacerbation 1, 2, 3
• Avoid using faster tapers than 50% reduction per week for aripiprazole—more rapid discontinuation increases risk of withdrawal symptoms and treatment failure 1, 3
• Do not expect immediate therapeutic effect from brexpiprazole—full efficacy may require 1-4 weeks at target dose, similar to aripiprazole's delayed onset of action 6, 5
• Avoid premature dose escalation of brexpiprazole—allow at least 1-2 weeks at each dose level to assess tolerability and response before increasing 6, 5
• Do not overlook the need for continued monitoring after week 4—some patients may require dose adjustments or management of emerging side effects beyond the initial transition period 6, 3

Special Considerations for Specific Populations

Patients with renal impairment: Maximum brexpiprazole dose should not exceed 3 mg daily in severe renal impairment; adjust tapering schedule accordingly 2

Patients with hepatic impairment: Similar dose restrictions apply; consider slower titration and lower target doses 2

Patients with history of poor medication adherence: The gradual cross-titration approach provides a safety buffer if doses are missed during the transition period 6, 8

Elderly patients: Consider starting brexpiprazole at 0.5-1 mg daily and using a more conservative tapering schedule (3-4 weeks total) to minimize risk of adverse effects 6