Brexpiprazole (Rexulti) 0.5 mg BID Prescription
This dosing regimen is not recommended and should be corrected to once-daily dosing. Brexpiprazole is FDA-approved for once-daily administration only, and prescribing it twice daily (BID) deviates from evidence-based dosing guidelines and may increase adverse effects without improving efficacy 1.
Correct Dosing for Brexpiprazole
For Major Depressive Disorder (Adjunctive Treatment)
The recommended starting dose is 0.5 mg or 1 mg orally once daily, not twice daily 1. The proper titration schedule is:
- Starting dose: 0.5 mg once daily OR 1 mg once daily
- Titration: Increase to 1 mg once daily, then to target dose of 2 mg once daily based on clinical response and tolerability, with increases at weekly intervals 1
- Target dose: 2 mg once daily
- Maximum dose: 3 mg once daily 1
For Schizophrenia
The recommended starting dose is 1 mg orally once daily on Days 1-4 1. The proper titration schedule is:
- Days 1-4: 1 mg once daily
- Days 5-7: 2 mg once daily
- Day 8 onward: Can increase to maximum of 4 mg once daily based on clinical response and tolerability 1
- Target dose: 2-4 mg once daily
- Maximum dose: 4 mg once daily 1
Why BID Dosing is Inappropriate
Brexpiprazole has a long half-life that supports once-daily dosing 2. The FDA label explicitly states "once daily" administration for all approved indications 1. Clinical trials demonstrating efficacy used once-daily dosing regimens 2, 3. Splitting the dose to twice daily:
- Has no evidence supporting improved efficacy
- May increase the risk of adverse effects, particularly akathisia, which occurred in 5.5% of schizophrenia patients and 8.6% of MDD patients in clinical trials 3
- Deviates from the approved prescribing information without scientific rationale 1
Dose Adjustments Required for Specific Populations
Reduce the maximum dose to 2 mg once daily (for MDD) or 3 mg once daily (for schizophrenia) in patients with:
- Moderate to severe hepatic impairment (Child-Pugh score ≥7) 1
- Renal impairment with creatinine clearance <60 mL/minute 1
Administer half the recommended dose in patients who are:
- Known CYP2D6 poor metabolizers 1
- Taking strong CYP2D6 inhibitors (except in MDD, where dose adjustment is already factored into general recommendations) 1
- Taking strong CYP3A4 inhibitors 1
Administer one-quarter of the recommended dose in patients taking:
- Strong/moderate CYP2D6 inhibitors combined with strong/moderate CYP3A4 inhibitors 1
- Known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors 1
Double the recommended dose over 1-2 weeks in patients taking:
- Strong CYP3A4 inducers 1
Administration Details
Brexpiprazole can be taken with or without food 1. The medication should be taken at the same time each day to maintain consistent plasma levels 1.
Common Pitfalls to Avoid
- Never prescribe BID dosing: This is not supported by any clinical evidence and contradicts FDA labeling 1
- Do not rush titration: Weekly intervals for dose increases in MDD allow assessment of tolerability, particularly for akathisia 1
- Monitor for akathisia: This is the most common adverse effect, with a number needed to harm of 15 in MDD patients 3
- Check for drug interactions: CYP2D6 and CYP3A4 interactions require dose adjustments 1
- Assess renal and hepatic function: Impairment requires maximum dose reductions 1
Correct Prescription Format
For MDD (starting dose):
- Brexpiprazole 0.5 mg tablet, take 1 tablet by mouth once daily
For MDD (target dose after titration):
- Brexpiprazole 2 mg tablet, take 1 tablet by mouth once daily
For Schizophrenia (starting dose):
- Brexpiprazole 1 mg tablet, take 1 tablet by mouth once daily