What is the recommended dosing for Rexulti (brexpiprazole)?

Rexulti (Brexpiprazole) Dosing

For schizophrenia in adults, start brexpiprazole at 1 mg once daily for Days 1-4, increase to 2 mg daily on Days 5-7, then titrate to the target dose of 2-4 mg daily based on response, with 4 mg being the maximum recommended dose. 1

For adjunctive treatment of major depressive disorder in adults, start at 0.5-1 mg once daily, titrate to 1 mg daily, then increase to the target dose of 2 mg daily (with weekly titration intervals), with a maximum of 3 mg daily. 1

Schizophrenia Dosing Algorithm

Initial Titration:

• Days 1-4: 1 mg orally once daily 1
• Days 5-7: 2 mg orally once daily 1
• Day 8 onward: Increase to 4 mg daily if needed based on clinical response and tolerability 1

Target Maintenance Dose:

• The recommended target dosage range is 2-4 mg once daily 1
• The 4 mg dose demonstrates the highest antipsychotic efficacy for symptom reduction 2
• Clinical trials showed response rates of 45.5% vs 31.0% for placebo at recommended target doses (NNT = 7) 3

Major Depressive Disorder (Adjunctive) Dosing Algorithm

Initial Titration:

• Week 1: Start at 0.5 mg or 1 mg once daily 1
• Week 2: Increase to 1 mg once daily 1
• Week 3 onward: Titrate to target dose of 2 mg once daily 1
• Increase dosage at weekly intervals based on clinical response and tolerability 1

Target Maintenance Dose:

• 2 mg once daily is the recommended target dose 1, 4
• Maximum dose is 3 mg once daily 1
• Clinical trials showed response rates of 23.2% vs 14.5% for placebo at 1-3 mg doses (NNT = 12) 3

Dosage Modifications for Special Populations

Hepatic Impairment (Child-Pugh score ≥7):

• MDD: Maximum 2 mg once daily 1
• Schizophrenia: Maximum 3 mg once daily 1

Renal Impairment (CrCl <60 mL/min):

• MDD: Maximum 2 mg once daily 1
• Schizophrenia: Maximum 3 mg once daily 1

CYP2D6 Poor Metabolizers:

• Administer half of the recommended dosage 1
• If also taking strong/moderate CYP3A4 inhibitors, administer one quarter of the recommended dosage 1

Drug Interactions Requiring Dose Adjustment:

• Strong CYP2D6 inhibitors: Reduce to half the recommended dose 1
• Strong CYP3A4 inhibitors: Reduce to half the recommended dose 1
• Strong/moderate CYP2D6 + CYP3A4 inhibitors combined: Reduce to one quarter of the recommended dose 1
• Strong CYP3A4 inducers: Double the recommended dose over 1-2 weeks 1
• When discontinuing the interacting drug, adjust brexpiprazole back to original level (over 1-2 weeks for inducers) 1

Administration Details

• Administer once daily with or without food 1
• Periodically reassess to determine continued need and appropriate dosage 1

Clinical Efficacy Context

Schizophrenia:

• Produces statistically significant improvements in overall symptomatology and psychosocial functioning 5
• In maintenance treatment (1-4 mg/day), significantly delays time to relapse: 13.5% vs 38.5% for placebo (NNT = 4) 3
• Reduces positive, negative, and depressive symptoms, as well as anxiety 2

Major Depressive Disorder:

• More effective than antidepressant monotherapy in patients with incomplete response to previous antidepressant treatment 4
• Improves depressive symptoms with adjunctive therapy 4

Safety Profile

• Discontinuation due to adverse events: 3% for MDD vs 1% placebo (NNH = 53) 3
• Akathisia incidence: 5.5% in schizophrenia trials, 8.6% in MDD trials 3
• Lower intrinsic D2 receptor activity than aripiprazole, predicting lower propensity for activating adverse events and extrapyramidal symptoms 5, 2
• Moderate weight gain with small, non-clinically significant changes in metabolic parameters 5
• Minimal prolactin effects and no clinically relevant QT interval changes 3