Switching from Aripiprazole 6mg to Brexpiprazole
For switching from aripiprazole (Abilify) 6mg to brexpiprazole (Rexulti), use a cross-taper approach: start brexpiprazole at 1mg daily while continuing aripiprazole 6mg, then reduce aripiprazole by 25% every 1-2 weeks while titrating brexpiprazole to target dose, completing the transition over 4-6 weeks.
Rationale for Cross-Tapering Strategy
Both aripiprazole and brexpiprazole are partial dopamine agonists with similar mechanisms of action, which allows for a relatively straightforward transition 1. Cross-tapering is the preferred method for antipsychotic switching because it minimizes the risk of symptom exacerbation while avoiding abrupt discontinuation effects 2, 1.
- Meta-analysis data shows no significant clinical differences between immediate versus gradual discontinuation strategies, but gradual tapering remains prudent for antipsychotics to avoid rebound symptoms 3, 1.
- The American Geriatrics Society recommends reducing antipsychotic doses by 25% every 2-4 weeks with careful monitoring for withdrawal symptoms including dyskinesias, parkinsonian symptoms, and dystonias 4.
Specific Switching Protocol
Week 1-2:
- Start brexpiprazole 1mg daily while maintaining aripiprazole 6mg 2, 5.
- Monitor for additive side effects, particularly akathisia, which can occur with both agents 5.
Week 3-4:
- Reduce aripiprazole to 4.5mg (25% reduction) while increasing brexpiprazole to 2mg if tolerated 4, 5.
- Assess clinical stability and emergence of any withdrawal symptoms 3.
Week 5-6:
- Reduce aripiprazole to 3mg while maintaining or adjusting brexpiprazole dose based on response 4.
- Continue monitoring for symptom breakthrough 3.
Week 7-8:
- Discontinue aripiprazole entirely once brexpiprazole reaches therapeutic dose (typically 2-4mg daily) 4, 5.
Critical Monitoring Parameters
Monitor at each dose reduction for:
- Withdrawal symptoms: anxiety, agitation, insomnia, movement disorders (dyskinesias, akathisia, parkinsonian symptoms) 4.
- Return of psychiatric symptoms: psychosis, mood instability, agitation 3.
- Overlapping side effects: akathisia is particularly common with both agents and may worsen during cross-titration 5.
The American Geriatrics Society emphasizes that the complete switching process should take 4-6 weeks minimum to allow adequate observation periods between dose changes 4.
Important Clinical Considerations
- Aripiprazole has a long half-life (75 hours), so therapeutic effects persist for several days after dose reduction, which provides a safety buffer during the switch 5.
- If severe or intolerable side effects emerge with either medication during the switch, immediate discontinuation of the offending agent may be necessary rather than continuing the gradual taper 3, 2.
- Both medications should be taken at consistent times daily, and brexpiprazole should be started at the target dose for the patient's symptoms rather than requiring extensive titration 2.
Common Pitfalls to Avoid
- Do not abruptly stop aripiprazole without initiating brexpiprazole, as this creates an unnecessary treatment gap and increases relapse risk 6, 1.
- Avoid rushing the cross-taper faster than 1-2 weeks per dose reduction, as this increases withdrawal symptom risk 4.
- Do not continue both medications at full doses for extended periods, as prolonged antipsychotic polypharmacy increases side effect burden without clear benefit 1.