What is the recommended dose of Rexulti (brexpiprazole) for schizophrenia and major depressive disorder?

Recommended Dosing of Brexpiprazole (Rexulti) for Schizophrenia and Major Depressive Disorder

For schizophrenia, the recommended dose of brexpiprazole is 2-4 mg once daily, starting at 1 mg daily for 4 days, then increasing to 2 mg daily on days 5-7, with potential increase to 4 mg daily on day 8 based on clinical response and tolerability. For major depressive disorder (MDD), the recommended dose is 2 mg once daily as adjunctive therapy, starting at 0.5-1 mg daily and titrating weekly 1.

Dosing for Schizophrenia

Initial Titration Schedule:

• Days 1-4: 1 mg once daily
• Days 5-7: 2 mg once daily
• Day 8 and beyond: Can increase to 4 mg once daily based on clinical response and tolerability

Target Dose Range:

• 2-4 mg once daily 1
• Maintain treatment for at least 4 weeks before determining efficacy 2

Maintenance Therapy:

• Continue effective dose for at least 1-2 years after initial episode of first-episode psychosis 2
• Periodic reassessment to determine continued need and appropriate dosage 1

Dosing for Major Depressive Disorder (Adjunctive Treatment)

Initial Titration Schedule:

• Starting dose: 0.5 mg or 1 mg once daily
• Titrate to 1 mg once daily, then to target dose of 2 mg once daily at weekly intervals

Target Dose:

• 2 mg once daily 1
• Maximum recommended daily dosage: 3 mg 1

Special Dosing Considerations

Hepatic Impairment:

• Moderate to severe hepatic impairment (Child-Pugh score ≥7):
  • MDD: Maximum 2 mg once daily
  • Schizophrenia: Maximum 3 mg once daily 1

Renal Impairment:

• CrCl <60 mL/minute:
  • MDD: Maximum 2 mg once daily
  • Schizophrenia: Maximum 3 mg once daily 1

CYP2D6 Poor Metabolizers and Drug Interactions:

• CYP2D6 poor metabolizers: Administer half of the recommended dosage
• Strong CYP2D6 inhibitors: Administer half of the recommended dosage
• Strong CYP3A4 inhibitors: Administer half of the recommended dosage
• Strong CYP3A4 inducers: Double the recommended dosage over 1-2 weeks 1

Efficacy and Response Rates

In clinical trials for schizophrenia, brexpiprazole showed:

• Response rates of 45.5% vs. 31.0% for placebo (NNT of 7) 3, 4
• In maintenance treatment, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%, NNT of 4) 3

For MDD as adjunctive therapy:

• Response rates of 23.2% vs. 14.5% for placebo (NNT of 12) 4

Monitoring and Side Effects

Common Side Effects:

• Weight gain is the most common adverse event (≥4% and at least twice the rate of placebo)
• Approximately 10% of patients gain ≥7% body weight from baseline (vs. 4% for placebo) 3
• Akathisia rates: 5.5% for schizophrenia and 8.6% for MDD 4

Monitoring Recommendations:

• Before starting: Obtain BMI, waist circumference, blood pressure, HbA1c, glucose, lipids, prolactin, liver function tests, electrolytes, full blood count, and ECG 5
• Recheck fasting glucose 4 weeks after initiation 5
• Monitor for metabolic side effects throughout treatment

Administration

• Administer once daily with or without food 1
• For patients switching from other antipsychotics, consider a gradual cross-titration to minimize risk of withdrawal symptoms

Brexpiprazole offers advantages of relatively low incidence of activating and sedating adverse effects, minimal effects on prolactin, and no clinically relevant effects on ECG QT interval 3, 6.