What is the recommended dosage and usage of Rexulti (brexpiprazole) for treating schizophrenia and major depressive disorder?

Recommended Dosage and Usage of Rexulti (Brexpiprazole) for Schizophrenia and Major Depressive Disorder

For the treatment of schizophrenia, Rexulti (brexpiprazole) should be started at 1 mg/day for 4 days, then increased to 2 mg/day by day 5-7, with a target dose of 2-4 mg/day and maximum dose of 4 mg/day. For adjunctive treatment of major depressive disorder (MDD), start with 0.5-1 mg/day and titrate to the target dose of 2 mg/day, with a maximum dose of 3 mg/day. 1

Dosing Recommendations by Indication

Schizophrenia

• Start with 1 mg once daily for days 1-4 1
• Increase to 2 mg once daily on days 5-7 1
• Target maintenance dose range: 2-4 mg once daily 1
• Maximum recommended dose: 4 mg once daily 1
• Long-term maintenance treatment is recommended for at least 1-2 years after the initial episode to prevent relapse 2

Major Depressive Disorder (Adjunctive Treatment)

• Start with 0.5 mg or 1 mg once daily 1
• Titrate to 1 mg once daily, then to the target dose of 2 mg once daily at weekly intervals 1
• Maximum recommended dose: 3 mg once daily 1
• Periodically reassess to determine continued need and appropriate dosage 1

Special Population Dosing Considerations

Hepatic Impairment

• For moderate to severe hepatic impairment (Child-Pugh score ≥7): 1
  • Maximum 2 mg once daily for MDD
  • Maximum 3 mg once daily for schizophrenia

Renal Impairment

• For creatinine clearance <60 mL/minute: 1
  • Maximum 2 mg once daily for MDD
  • Maximum 3 mg once daily for schizophrenia

CYP2D6 Poor Metabolizers and Drug Interactions

• For CYP2D6 poor metabolizers: Administer half of the recommended dosage 1
• With strong CYP3A4 inhibitors: Administer half of the recommended dosage 1
• With strong/moderate CYP2D6 inhibitors plus strong/moderate CYP3A4 inhibitors: Administer a quarter of the recommended dosage 1
• With strong CYP3A4 inducers: Double the recommended dosage over 1-2 weeks 1
• Note: For MDD treatment, dosage adjustment is not needed when used with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) 1

Administration Guidelines

• Administer once daily with or without food 1
• Adequate therapeutic trials generally require sufficient dosages over a period of 4-6 weeks 2
• For schizophrenia, treatment response should be documented, with target symptoms monitored 2
• For MDD, brexpiprazole should only be used as adjunctive therapy with antidepressants, not as monotherapy 1

Clinical Efficacy and Tolerability

Efficacy

• In schizophrenia trials, pooled responder rates were 46% for brexpiprazole 2-4 mg/day versus 31% for placebo (NNT=7) 3, 4
• In a 52-week relapse prevention study, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%, NNT=4) 3, 4
• For adjunctive MDD treatment, response rates were 23.2% with brexpiprazole versus 14.5% with placebo (NNT=12) 4

Common Adverse Effects

• Most common adverse event is weight gain (≥4% and at least twice the rate of placebo in schizophrenia) 1, 3
• Approximately 10% of patients receiving brexpiprazole 1-4 mg/day gained ≥7% body weight from baseline (versus 4% for placebo) 3, 4
• Akathisia rates were 5.5% for schizophrenia and 8.6% for MDD 3, 4
• Effects on glucose, lipids, and prolactin were minimal 3, 4
• No clinically relevant effects on ECG QT interval were observed 3, 4

Monitoring Recommendations

• Document target symptoms and treatment response 2
• Monitor for side effects, particularly weight gain and akathisia 1, 3
• Perform baseline and follow-up laboratory monitoring as appropriate for the medication 2
• For schizophrenia, reassess dosage needs based on the stage of illness (higher doses may be required during acute phases, with smaller doses during residual phases) 2

Clinical Considerations

• Brexpiprazole is a serotonin-dopamine activity modulator with partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors, and antagonist activity at serotonin 5-HT2A receptors 3, 5
• Compared to aripiprazole (another D2 partial agonist), brexpiprazole has less intrinsic activity at D2 receptors and higher potency at 5-HT1A, 5-HT2A, and α1B receptors, potentially leading to a more tolerable side effect profile regarding akathisia and extrapyramidal symptoms 6
• The pharmacological profile of brexpiprazole may offer advantages in terms of reduced akathisia compared to other antipsychotics, though direct head-to-head comparisons are needed 6