What is the recommended starting dose of Rexulti (brexpiprazole)?

Rexulti (Brexpiprazole) Starting Dose

For major depressive disorder (MDD), start brexpiprazole at 0.5 mg or 1 mg orally once daily; for schizophrenia, start at 1 mg orally once daily. 1

Starting Dose by Indication

Major Depressive Disorder (Adjunctive Treatment)

• Initial dose: 0.5 mg or 1 mg once daily 1
• Titrate to 1 mg once daily if starting at 0.5 mg, then increase to the target dose of 2 mg once daily based on clinical response and tolerability 1
• Increase dosage at weekly intervals 1
• Maximum recommended dose: 3 mg daily 1

Schizophrenia

• Initial dose: 1 mg once daily on Days 1-4 1
• Titrate to 2 mg once daily on Days 5-7 1
• On Day 8, may increase to maximum recommended dose of 4 mg based on clinical response and tolerability 1
• Target dose range: 2-4 mg once daily 1, 2

Administration Details

• Administer once daily with or without food 1
• The recommended titration schedule for schizophrenia is to start with 1 mg/day and increase to 2 mg/day on Day 5 to Day 7, then to 4 mg/day on Day 8 2

Dosage Modifications for Special Populations

Hepatic Impairment

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

Renal Impairment

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

CYP2D6 Poor Metabolizers and Drug Interactions

• CYP2D6 poor metabolizers: Administer half of the recommended dosage 1
• Strong CYP2D6 or CYP3A4 inhibitors: Administer half of the recommended dosage 1
• Strong/moderate CYP2D6 with strong/moderate CYP3A4 inhibitors: Administer a quarter of the recommended dosage 1
• Strong CYP3A4 inducers: Double the recommended dosage over 1-2 weeks 1
• Important exception: For MDD patients, dosage adjustment is not required when co-administered with strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) as this was already factored into clinical trial dosing 1

Clinical Evidence Supporting Dosing

Efficacy Data

• In acute schizophrenia trials, the pooled responder rate for brexpiprazole 2-4 mg/day was 46% versus 31% for placebo, yielding a number needed to treat (NNT) of 7 2
• In the 52-week relapse prevention study, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%), resulting in an NNT of 4 2
• For MDD, pooled results showed 23.2% responders with brexpiprazole versus 14.5% for placebo, yielding an NNT of 12 3

Tolerability Profile

• Short-term weight gain is modest, with approximately 10% of patients receiving brexpiprazole 1-4 mg/day gaining ≥7% body weight versus 4% for placebo (NNH of 17) 2
• Akathisia rates were 5.5% for brexpiprazole 1-4 mg/day versus 4.6% for placebo (NNH of 112) 2
• Discontinuation rates due to adverse events were generally lower than placebo in schizophrenia trials 3

Critical Monitoring During Titration

• Monitor for akathisia, particularly during the first 1-4 weeks of treatment 4
• Assess for metabolic changes including weight gain, hyperglycemia, and dyslipidemia 1
• Periodically reassess to determine continued need and appropriate dosage for treatment 1