Rexulti Starting Dose
For major depressive disorder (MDD), start Rexulti at 0.5 mg or 1 mg once daily; for schizophrenia in adults, start at 1 mg once daily; for schizophrenia in adolescents (13-17 years), start at 0.5 mg once daily; and for agitation in Alzheimer's dementia, start at 0.5 mg once daily. 1
Dosing by Indication
Major Depressive Disorder (Adults)
- Starting dose: 0.5 mg or 1 mg once daily
- Titration: Increase to 1 mg daily, then to target dose of 2 mg daily based on response and tolerability
- Titration interval: Weekly increments
- Target dose: 2 mg once daily
- Maximum dose: 3 mg once daily 1
Schizophrenia (Adults)
- Starting dose: 1 mg once daily (Days 1-4)
- Titration: Increase to 2 mg daily on Days 5-7, then may increase to 4 mg on Day 8
- Target dose: 2-4 mg once daily
- Maximum dose: 4 mg once daily 1
Schizophrenia (Adolescents 13-17 years)
- Starting dose: 0.5 mg once daily (Days 1-4)
- Titration: Increase to 1 mg daily on Days 5-7, then to 2 mg on Day 8
- Further titration: Weekly 1 mg increments as needed
- Target dose: 2-4 mg once daily
- Maximum dose: 4 mg once daily 1
Agitation in Alzheimer's Dementia
- Starting dose: 0.5 mg once daily (Days 1-7)
- Titration: Increase to 1 mg daily on Days 8-14, then to 2 mg on Day 15
- Target dose: 2 mg once daily
- Maximum dose: 3 mg once daily (after at least 14 days at 2 mg) 1
Administration Details
Administer once daily with or without food. The medication can be taken at any time of day, providing flexibility for patient adherence 1.
Dose Adjustments for Special Populations
Hepatic Impairment
For moderate to severe hepatic impairment (Child-Pugh score ≥7):
- MDD or Alzheimer's agitation: Maximum 2 mg daily
- Schizophrenia: Maximum 3 mg daily 1
Renal Impairment
For creatinine clearance <60 mL/minute:
- MDD or Alzheimer's agitation: Maximum 2 mg daily
- Schizophrenia: Maximum 3 mg daily 1
CYP2D6 Poor Metabolizers
Administer half of the recommended dosage in known CYP2D6 poor metabolizers. If also taking strong/moderate CYP3A4 inhibitors, administer one quarter of the recommended dosage 1.
Clinical Considerations
The gradual titration schedule is critical to minimize gastrointestinal adverse effects and akathisia. Research demonstrates that brexpiprazole requires 6-12 weeks to separate from placebo in efficacy trials, particularly for Alzheimer's-related agitation 2. This means patience is essential—do not abandon treatment prematurely if response is not immediate.
For MDD, the 2 mg dose provides optimal benefit with a number needed to treat (NNT) of 12, while maintaining favorable tolerability 3. For schizophrenia, the 2-4 mg range shows an NNT of 7 for acute treatment and an impressive NNT of 4 for relapse prevention 4, 3.
Weight gain is modest in short-term studies (approximately 10% of patients gain ≥7% body weight vs 4% on placebo), but monitor carefully during long-term treatment as more outliers emerge 4, 5. Akathisia rates are low (5.5% vs 4.6% placebo in schizophrenia, yielding NNH of 112), and sedation is minimal 4, 5, 3.