Brexpiprazole (Rexulti) Dosing for Schizophrenia and Major Depressive Disorder
The recommended dosing for brexpiprazole in schizophrenia is 1 mg/day initially, titrated to 2 mg by day 5-7, with a target dose of 2-4 mg/day (maximum 4 mg/day). For major depressive disorder, start with 0.5-1 mg/day and titrate to a target dose of 2 mg/day (maximum 3 mg/day). 1
Dosing for Schizophrenia
- Initial dosing: Start with 1 mg once daily for days 1-4 1
- Titration: Increase to 2 mg once daily on days 5-7 1
- Target dose: 2-4 mg once daily based on clinical response and tolerability 1
- Maximum dose: 4 mg once daily 1
Brexpiprazole acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A and adrenergic alpha1B/alpha2C receptors 2. This pharmacological profile contributes to its efficacy in treating positive symptoms of schizophrenia.
Clinical trials have demonstrated efficacy in acute schizophrenia with pooled responder rates of 46% for brexpiprazole 2-4 mg/day versus 31% for placebo (NNT of 7) 2. In maintenance treatment, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%, NNT of 4) 2, 3.
Dosing for Major Depressive Disorder (Adjunctive Treatment)
- Initial dosing: Start with 0.5 mg or 1 mg once daily 1
- Titration: Titrate to 1 mg once daily, then to the target dose of 2 mg once daily at weekly intervals 1
- Target dose: 2 mg once daily 1
- Maximum dose: 3 mg once daily 1
- Administration: Take once daily with or without food 1
As an adjunctive treatment for MDD, brexpiprazole has demonstrated efficacy with a number needed to treat (NNT) of 12 for response 3. When added to antidepressants in patients with inadequate response, brexpiprazole 2-3 mg/day showed greater improvement in Montgomery-Åsberg Depression Rating Scale scores compared to placebo (effect size: 0.33) 4.
Special Population Considerations
Hepatic Impairment
- Moderate to severe impairment (Child-Pugh score ≥7):
- Maximum 2 mg once daily for MDD
- Maximum 3 mg once daily for schizophrenia 1
Renal Impairment
- CrCl <60 mL/minute:
- Maximum 2 mg once daily for MDD
- Maximum 3 mg once daily for schizophrenia 1
CYP2D6 Poor Metabolizers and Drug Interactions
- CYP2D6 poor metabolizers: Administer half of the recommended dosage 1
- Strong CYP3A4 inhibitors: Administer half of the recommended dosage 1
- Strong/moderate CYP2D6 inhibitors 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
Note: In MDD treatment, dosage adjustment is not needed for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) as this interaction was already factored into the dosing recommendations from clinical trials 1.
Common Adverse Effects and Monitoring
- Weight gain: Approximately 10% of patients on brexpiprazole 1-4 mg/day gained ≥7% body weight (NNH of 17) 2, 3
- Akathisia: Rates were 5.5% for schizophrenia (NNH of 112) and 8.6% for MDD (NNH of 15) 2, 3
- Other common adverse effects: Headache (5.8%), somnolence, and gastrointestinal side effects 2, 5, 4
Brexpiprazole has minimal effects on prolactin levels and no clinically relevant effects on QTc interval 2, 3. It shows a more favorable profile regarding akathisia compared to aripiprazole but may cause more weight gain 5.
Clinical Pearls
- Brexpiprazole has less intrinsic activity at D2 receptors than aripiprazole, potentially leading to fewer extrapyramidal symptoms 2, 5
- Once-daily dosing improves adherence 6
- Regular monitoring for metabolic changes is recommended, particularly weight gain 2
- Periodically reassess the need for continued treatment and appropriate dosage 1
Remember that brexpiprazole carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis and suicidal thoughts/behaviors in pediatric and young adult patients 1.