Brexpiprazole (Brexaulti) Treatment Indications
Brexpiprazole is FDA-approved for the treatment of schizophrenia and as an adjunctive treatment for major depressive disorder (MDD) in adults. 1
Approved Indications
1. Schizophrenia
- Brexpiprazole is effective as monotherapy for treating acute schizophrenia and for maintenance treatment to prevent relapse
- Recommended dosage: 2-4 mg once daily 1
- Titration schedule:
- Start with 1 mg/day (Days 1-4)
- Increase to 2 mg/day (Days 5-7)
- May increase to 4 mg/day (Day 8 onward) if needed
2. Major Depressive Disorder (MDD)
- Approved as an adjunctive treatment to antidepressant therapy (ADT) for patients with inadequate response to antidepressant treatment alone
- Recommended dosage: 2 mg once daily 1
- Titration schedule:
- Start with 0.5 mg/day (Week 1)
- Increase to 1 mg/day (Week 2)
- Increase to 2 mg/day (Week 3 onward)
Pharmacological Properties
Brexpiprazole is a third-generation antipsychotic that acts as:
- Partial agonist at dopamine D2 receptors (with less intrinsic activity than aripiprazole)
- Partial agonist at serotonin 5-HT1A receptors
- Antagonist at serotonin 5-HT2A receptors
- Antagonist at adrenergic alpha1B and alpha2C receptors 2
Efficacy Data
For Schizophrenia:
- Pooled responder rates: 46% for brexpiprazole 2-4 mg/day vs. 31% for placebo (NNT of 7) 2
- In maintenance treatment, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%), resulting in an NNT of 4 2
For MDD:
- When used as adjunctive therapy with antidepressants, brexpiprazole showed superior efficacy compared to placebo in reducing depressive symptoms 1
- Response rates: 23.2% for brexpiprazole vs. 14.5% for placebo (NNT of 12) 3
Safety and Adverse Effects
- Most common adverse event: Weight gain (approximately 10% of patients on 1-4 mg/day gained ≥7% body weight vs. 4% on placebo) 2
- Akathisia rates: 5.5% for schizophrenia and 8.6% for MDD 3
- Minimal effects on prolactin levels
- No clinically relevant effects on ECG QTc interval
- Generally well-tolerated with low discontinuation rates due to adverse events 2, 3
Special Populations
- Dose adjustments should be considered in:
- Hepatic or renal dysfunction
- Poor CYP2D6 metabolizers 4
Clinical Considerations
- Brexpiprazole has a more favorable side effect profile regarding akathisia and extrapyramidal symptoms compared to some other antipsychotics 4
- In patients with MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and may reduce anxiety symptoms 5
- Once-daily dosing makes it convenient for patients
While brexpiprazole is classified as a third-generation antipsychotic along with aripiprazole, cariprazine, and lumateperone 6, it is important to note that it is not currently FDA-approved for bipolar disorder or other conditions that some antipsychotics may treat.