Rexulti (Brexpiprazole) Dosing and Recommended Use for Schizophrenia and Major Depressive Disorder
Brexpiprazole (Rexulti) is FDA-approved for the treatment of schizophrenia in adults (2-4 mg/day) and as adjunctive therapy for major depressive disorder in adults (2 mg/day). 1
Dosing for Schizophrenia
Initial Dosing and Titration
- Start with 1 mg once daily on days 1-4
- Increase to 2 mg once daily on days 5-7
- On day 8, may increase to the maximum recommended dose of 4 mg once daily based on clinical response and tolerability 1
- Target dosage range: 2-4 mg once daily 1
Efficacy in Schizophrenia
- Clinical trials demonstrated superiority over placebo with a number needed to treat (NNT) of 7 for response 2
- In maintenance treatment, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs 38.5%, NNT of 4) 2
Dosing for Major Depressive Disorder (Adjunctive Therapy)
Initial Dosing and Titration
- Start with 0.5 mg or 1 mg once daily
- Titrate to 1 mg once daily, then to target dose of 2 mg once daily (increase at weekly intervals based on clinical response and tolerability) 1
- Maximum recommended dose: 3 mg once daily 1
Special Populations
Hepatic Impairment
- For moderate to severe hepatic impairment (Child-Pugh score ≥7):
- Maximum dose for MDD: 2 mg once daily
- Maximum dose for schizophrenia: 3 mg once daily 1
Renal Impairment
- For creatinine clearance <60 mL/minute:
- Maximum dose for MDD: 2 mg once daily
- Maximum dose for schizophrenia: 3 mg once daily 1
CYP2D6 Poor Metabolizers
- Administer half of the recommended dosage
- If also taking strong/moderate CYP3A4 inhibitors, administer a quarter of the recommended dosage 1
Drug Interactions
CYP Inhibitors
- Strong CYP2D6 inhibitors: Administer half of recommended dosage (except in MDD where no adjustment is needed when used with strong CYP2D6 inhibitors like paroxetine or fluoxetine) 1
- Strong CYP3A4 inhibitors: Administer half of recommended dosage
- Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors: Administer a quarter of the recommended dosage 1
CYP Inducers
- Strong CYP3A4 inducers: Double the recommended dosage over 1-2 weeks 1
- If the inducer is discontinued, reduce the brexpiprazole dosage to original level over 1-2 weeks 1
Administration
- Administer once daily with or without food 1
Safety Considerations
Common Adverse Effects
- Schizophrenia: Weight gain (≥4% and at least twice the rate for placebo) 1
- MDD: Weight gain, somnolence, and akathisia (≥5% and at least twice the rate for placebo) 1
- Akathisia rates appear lower compared to other D2 partial agonists like aripiprazole 3
Monitoring
- Regular assessment of treatment response and adverse effects beginning within 1-2 weeks of initiation 4
- Monitor for weight gain, metabolic changes, and extrapyramidal symptoms 2
- For MDD treatment, monitor for suicidal thoughts/behaviors, especially in the first 1-2 months 4
Treatment Duration
- For schizophrenia: Long-term maintenance therapy is typically required 5
- For MDD (first episode): Continue treatment for 4-9 months after achieving remission 4
- For recurrent MDD (2+ episodes): Years to lifelong treatment may be beneficial 4
Clinical Advantages
- Brexpiprazole has less intrinsic activity at D2 receptors than aripiprazole, which may contribute to a more tolerable side effect profile regarding akathisia and extrapyramidal symptoms 3
- Generally well tolerated with relatively low incidence of activating and sedating adverse effects 6
Contraindications
- Known hypersensitivity to brexpiprazole or any of its components 1
Important Warnings
- Increased mortality in elderly patients with dementia-related psychosis (not approved for this indication) 1
- Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients with MDD 1
Brexpiprazole represents a valuable option for treating schizophrenia and as adjunctive therapy for MDD, with a pharmacological profile that may offer advantages in terms of tolerability compared to some other antipsychotics.