What is the recommended dosage of Rexulti (brexpiprazole)?

Rexulti (Brexpiprazole) Dosage

For schizophrenia in adults, start brexpiprazole at 1 mg once daily for Days 1-4, increase to 2 mg daily on Days 5-7, with a target dose of 2-4 mg daily (maximum 4 mg/day); for adjunctive treatment of major depressive disorder, start at 0.5-1 mg daily, titrate to target dose of 2 mg daily (maximum 3 mg/day). 1

Schizophrenia Dosing (Adults)

Initial Titration Schedule:

• Days 1-4: 1 mg orally once daily 1
• Days 5-7: 2 mg orally once daily 1
• Day 8 onwards: Can increase to maximum 4 mg daily based on clinical response 1

Target Maintenance Dose:

• Recommended target: 2-4 mg once daily 1
• Maximum dose: 4 mg once daily 1
• Clinical trials demonstrated efficacy at 2-4 mg/day with response rates of 45.5% versus 31.0% for placebo (NNT=7) 2

The 4 mg dose showed the highest antipsychotic efficacy in reducing positive, negative, and depressive symptoms 3. In maintenance treatment, brexpiprazole 1-4 mg/day significantly delayed time to relapse (13.5% vs 38.5% for placebo, NNT=4) 2.

Major Depressive Disorder Dosing (Adjunctive Treatment)

Initial Titration:

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

Target Maintenance Dose:

• Recommended target: 2 mg once daily 1
• Maximum dose: 3 mg once daily 1
• Pooled trial data showed 23.2% response rate versus 14.5% for placebo at 1-3 mg doses (NNT=12) 2

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 recommended dosage 1

Drug Interactions Requiring Dose Adjustment:

• Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine): Reduce to half the recommended dose 1
• Strong CYP3A4 inhibitors: Reduce to half the recommended dose 1
• Combined strong/moderate CYP2D6 and CYP3A4 inhibitors: Reduce to one quarter of recommended dose 1
• Strong CYP3A4 inducers: Double the dose over 1-2 weeks 1

Important caveat: For MDD patients, dosage adjustment for strong CYP2D6 inhibitors is already factored into general dosing recommendations, so no additional adjustment is needed 1.

Administration Details

• Administer once daily with or without food 1
• Titration helps reduce gastrointestinal adverse effects 1
• Periodically reassess to determine continued need and appropriate dosage 1
• When discontinuing concomitant CYP3A4 inducers, reduce brexpiprazole dose to original level over 1-2 weeks 1

Tolerability Profile

The most common adverse effect is akathisia (5.5% in schizophrenia trials, 8.6% in MDD trials), though differences from placebo are modest (NNH=15 for MDD) 2. Discontinuation rates due to adverse events were 3% for brexpiprazole versus 1% for placebo in MDD trials (NNH=53) 2. Weight gain appears modest in short-term studies, though more outliers with ≥7% body weight increase were observed in 52-week open-label studies 2.