Rexulti (Brexpiprazole) Dosing and Usage
For schizophrenia, start brexpiprazole at 1 mg daily, increase to 2 mg on days 5-7, then target 2-4 mg daily; for major depressive disorder as adjunctive therapy, start at 0.5-1 mg daily and titrate weekly to a target of 2 mg daily (maximum 3 mg). 1
Schizophrenia Treatment
Initial Dosing and Titration
- Start at 1 mg orally once daily on Days 1-4 1
- Increase to 2 mg once daily on Days 5-7 1
- On Day 8, may increase to 4 mg daily based on clinical response and tolerability 1
- Target dose range: 2-4 mg once daily 1
- Maximum dose: 4 mg daily 1
Efficacy Evidence
- Brexpiprazole 2-4 mg/day demonstrated 45.5% responder rate versus 31% for placebo in acute schizophrenia, yielding a number needed to treat (NNT) of 7 2, 3
- In maintenance treatment, only 13.5% relapsed on brexpiprazole versus 38.5% on placebo, with an NNT of 4 2, 3
- The drug showed superiority over placebo in two 6-week Phase 3 trials for acute schizophrenia 2
Major Depressive Disorder (Adjunctive Treatment)
Initial Dosing and Titration
- Start at 0.5 mg or 1 mg orally once daily 1
- Titrate to 1 mg once daily, then increase to target dose of 2 mg daily 1
- Increase dosage at weekly intervals based on clinical response and tolerability 1
- Maximum dose: 3 mg daily 1
Efficacy Evidence
- Pooled responder rate of 23.2% versus 14.5% for placebo, yielding an NNT of 12 3
- NNT for remission ranges from 17-31 versus placebo 4
Administration Details
- Administer once daily with or without food 1
- Periodically reassess to determine continued need and appropriate dosage 1
Dosage Adjustments
Hepatic Impairment
- Maximum 2 mg daily for MDD patients with moderate to severe hepatic impairment (Child-Pugh score ≥7) 1
- Maximum 3 mg daily for schizophrenia patients with moderate to severe hepatic impairment 1
Renal Impairment
- Maximum 2 mg daily for MDD patients with CrCl <60 mL/minute 1
- Maximum 3 mg daily for schizophrenia patients with CrCl <60 mL/minute 1
CYP2D6 Poor Metabolizers and Drug Interactions
- For CYP2D6 poor metabolizers: administer half the recommended dosage 1
- With strong CYP2D6 or CYP3A4 inhibitors: administer half the recommended dosage 1
- With strong/moderate CYP2D6 AND strong/moderate CYP3A4 inhibitors: administer one quarter of the recommended dosage 1
- With strong CYP3A4 inducers: double the recommended dosage over 1-2 weeks 1
- Important exception: For MDD patients taking strong CYP2D6 inhibitors (paroxetine, fluoxetine), no dosage adjustment needed as this was factored into clinical trials 1
Safety and Tolerability Profile
Common Adverse Effects
- Most common adverse reactions in MDD: weight gain, somnolence, and akathisia (≥5% and at least twice placebo rate) 1
- Most common adverse reaction in schizophrenia: weight gain (≥4% and at least twice placebo rate) 1
- Akathisia rates: 5.5% for brexpiprazole 1-4 mg/day versus 4.6% for placebo (NNH of 112 in schizophrenia) 2, 3
- Akathisia rates in MDD: 8.6% with NNH of 15 3
Weight and Metabolic Effects
- Approximately 10% of patients receiving 1-4 mg/day gained ≥7% body weight versus 4% on placebo (NNH of 17) 2
- More outliers with ≥7% weight gain evident in 52-week open-label studies 2, 3
- Effects on glucose and lipids were small 2, 3
- Minimal effects on prolactin observed 2, 3
Discontinuation Rates
- In schizophrenia trials: discontinuation due to adverse events was 7.1-9.2% for brexpiprazole versus 14.7% for placebo 4
- In MDD trials: discontinuation due to adverse events was 1.3-3.5% for brexpiprazole versus 0-1.4% for placebo (NNH of 53) 4, 3
Critical Safety Warnings
Black Box Warnings
- Increased mortality risk in elderly patients with dementia-related psychosis—brexpiprazole is NOT approved for this indication 1
- Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients treated with antidepressants 1
- Safety and effectiveness NOT established in pediatric patients with MDD 1
Monitoring Requirements
- Monitor closely for clinical worsening and emergence of suicidal thoughts, especially within 1-2 weeks of initiation 1
- Monitor for metabolic changes including hyperglycemia, diabetes, dyslipidemia, and weight gain 1
- Monitor heart rate and blood pressure, particularly in patients with cardiovascular disease 1
Pharmacological Profile
- Brexpiprazole acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors 2, 5
- Acts as antagonist at serotonin 5-HT2A and adrenergic alpha1B and alpha2C receptors 2, 5
- Compared to aripiprazole: more potent at 5-HT1A receptors and displays less intrinsic activity at D2 receptors 2, 4
- This pharmacological profile suggests potentially lower akathisia and extrapyramidal symptoms compared to aripiprazole 4