Brexpiprazole (Rexulti) Dosing Recommendations
For adults with schizophrenia, start brexpiprazole at 1 mg once daily for days 1-4, increase to 2 mg once daily on days 5-7, then adjust to the target dose of 2-4 mg once daily based on clinical response and tolerability. 1
Dosing by Indication
Schizophrenia
- Initial dose: 1 mg once daily for days 1-4
- Titration: Increase to 2 mg once daily on days 5-7
- Target dose: 2-4 mg once daily
- Maximum dose: 4 mg once daily
Major Depressive Disorder (Adjunctive Treatment)
- Initial dose: 0.5 mg or 1 mg once daily
- Titration: Increase to 1 mg once daily, then to target dose at weekly intervals
- Target dose: 2 mg once daily
- Maximum dose: 3 mg once daily
Special Populations
Hepatic Impairment
- Moderate to severe impairment (Child-Pugh score ≥7):
- MDD: Maximum 2 mg once daily
- Schizophrenia: Maximum 3 mg once daily
Renal Impairment
- CrCl <60 mL/minute:
- MDD: Maximum 2 mg once daily
- Schizophrenia: Maximum 3 mg once daily
Dosage Modifications for Drug Interactions
CYP2D6 Poor Metabolizers
- Administer half of the recommended dosage
- If also taking strong/moderate CYP3A4 inhibitors: Administer quarter of the recommended dosage
Patients Taking CYP Inhibitors/Inducers
- Strong CYP2D6 inhibitors: Administer half of the recommended dosage*
- Strong CYP3A4 inhibitors: Administer half of the recommended dosage
- Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors: Administer quarter of the recommended dosage
- Strong CYP3A4 inducers: Double the recommended dosage over 1-2 weeks
*Note: For MDD treatment, no dosage adjustment needed with CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) as this was factored into clinical trials 1
Administration Guidelines
- Administer once daily with or without food
- When discontinuing or interrupting therapy, consider tapering the dose gradually to minimize withdrawal symptoms
Monitoring
- Monitor for common adverse effects:
- Weight gain (most common adverse effect in schizophrenia trials)
- Somnolence and akathisia (most common in MDD trials) 2
- Complete baseline assessment and periodic monitoring of metabolic parameters
- Monitor for extrapyramidal symptoms, though these occur at lower rates compared to some other antipsychotics 3
Clinical Considerations
- Brexpiprazole has a unique receptor binding profile with lower intrinsic D2 activity compared to aripiprazole, potentially resulting in fewer activation-like adverse effects such as akathisia 4
- In clinical trials, brexpiprazole demonstrated efficacy for schizophrenia with an NNT of 7 for acute treatment and NNT of 4 for maintenance treatment 2
- For adjunctive MDD treatment, brexpiprazole showed an NNT of 12 2
- Emerging research suggests potential utility in bipolar depression, though this remains an off-label use 5
Common Pitfalls to Avoid
- Starting at too high a dose, which may increase risk of adverse effects
- Failing to adjust dosage in patients with hepatic/renal impairment
- Not accounting for drug interactions, particularly with CYP2D6 and CYP3A4 inhibitors/inducers
- Abrupt discontinuation rather than gradual tapering
Remember that brexpiprazole is not approved for dementia-related psychosis due to increased mortality risk in elderly patients with dementia.