Brexpiprazole Starting Dose for Depression
The recommended starting dose of brexpiprazole (Rexulti) for treating depression is 0.5 mg or 1 mg orally once daily. 1
Dosing Algorithm for Brexpiprazole in Depression
Initial Dosing
- Start with 0.5 mg or 1 mg once daily with or without food
- Titrate to 1 mg once daily, then increase to the target dose of 2 mg once daily
- Dose increases should occur at weekly intervals based on clinical response and tolerability
- Maximum recommended daily dose: 3 mg 1
Dose Adjustments for Special Populations
Hepatic Impairment:
- For moderate to severe hepatic impairment (Child-Pugh score ≥7): Maximum dose of 2 mg once daily 1
Renal Impairment:
- For creatinine clearance <60 mL/minute: Maximum dose of 2 mg once daily 1
CYP2D6 Poor Metabolizers and Drug Interactions:
- CYP2D6 poor metabolizers: Administer half of the recommended dose
- Patients taking strong CYP2D6 inhibitors: Administer half of the recommended dose
- Patients taking strong CYP3A4 inhibitors: Administer half of the recommended dose
- Patients taking both strong/moderate CYP2D6 inhibitors and strong/moderate CYP3A4 inhibitors: Administer a quarter of the recommended dose
- Patients taking strong CYP3A4 inducers: Double the recommended dose over 1-2 weeks 1
Efficacy and Clinical Considerations
Recent evidence supports the efficacy of brexpiprazole as adjunctive therapy for major depressive disorder:
- A 2022 dose-effect meta-analysis found that 1-2 mg of brexpiprazole may achieve an optimal balance between efficacy, tolerability, and acceptability in antidepressant-refractory depression 2
- A 2024 Japanese study demonstrated that both 1 mg and 2 mg daily doses were effective and well-tolerated as adjunctive therapy for MDD patients with inadequate response to antidepressants 3
Common Side Effects and Monitoring
The most common adverse effects to monitor for include:
Important Precautions
- Periodically reassess: Determine the continued need and appropriate dosage for treatment
- Monitor for metabolic changes: Weight gain, hyperglycemia, and dyslipidemia
- Watch for akathisia: Though rates are relatively low compared to some other antipsychotics
- Suicidal thoughts and behaviors: Closely monitor all patients, especially during initial treatment and dose adjustments 1
Clinical Pearls
- Brexpiprazole should always be used as adjunctive therapy with antidepressants for MDD, not as monotherapy
- The target dose of 2 mg daily has shown the best balance of efficacy and tolerability in clinical trials 2
- Young adult patients (18-35 years) with MDD have shown improvements in work/school functioning with adjunctive brexpiprazole (target dose 2 mg/day) 5
- Patients with concurrent anxiety symptoms may also benefit from adjunctive brexpiprazole 6
Remember that brexpiprazole is indicated only as an adjunctive therapy to antidepressants for the treatment of major depressive disorder in adults, not as monotherapy.