What is the recommended use and dosage of Rexulti (brexpiprazole)?

Recommended Use and Dosage of Rexulti (Brexpiprazole)

Brexpiprazole (Rexulti) is indicated for the adjunctive treatment of major depressive disorder (MDD) in adults and for the treatment of schizophrenia in adults, with specific dosing regimens for each condition. 1

Indications and Dosing

Major Depressive Disorder (Adjunctive Treatment)

• Starting dose: 0.5 mg or 1 mg once daily
• Titration: Increase to 1 mg once daily, then to target dose of 2 mg once daily (increase at weekly intervals)
• Maximum dose: 3 mg once daily
• Administration: Take once daily with or without food 1

Schizophrenia

• Starting dose: 1 mg once daily for Days 1-4
• Titration: Increase to 2 mg once daily on Days 5-7
• Target dose: 2-4 mg once daily
• Maximum dose: 4 mg once daily
• Administration: Take once daily with or without food 1

Special Populations

Hepatic Impairment

• Moderate to severe 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 recommended dosage
• Strong CYP3A4 inhibitors: Administer half of recommended dosage
• Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors: Administer quarter of recommended dosage
• Strong CYP3A4 inducers: Double the recommended dosage over 1-2 weeks 1

Efficacy

• Schizophrenia: Pooled responder rates of 46% for brexpiprazole 2-4 mg/day vs. 31% for placebo (NNT of 7) 2
• Relapse prevention: Significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%, NNT of 4) 2
• MDD: When used as adjunctive therapy, brexpiprazole showed significantly higher response rates compared to placebo (23.2% vs. 14.5%, NNT of 12) 3

Adverse Effects

Common Adverse Effects

• MDD: Weight increase, somnolence, and akathisia (≥5% and at least twice the rate for placebo) 1
• Schizophrenia: Weight increase (≥4% and at least twice the rate for placebo) 1

Other Adverse Effects

• Akathisia: 5.5% in schizophrenia trials and 8.6% in MDD trials 3
• Metabolic effects: Modest short-term weight gain; approximately 10% of patients on 1-4 mg/day gained ≥7% body weight from baseline (vs. 4% for placebo) 2
• Minimal effects on prolactin, glucose, lipids, and ECG QTc interval 2, 4

Monitoring Recommendations

• Baseline: Complete blood count (CBC) and comprehensive metabolic panel
• Follow-up: Monitor every 2-4 weeks until doses are stabilized, then as clinically indicated
• Weight monitoring: Regular assessment due to potential for weight gain
• Symptom assessment: Periodic reassessment to determine continued need and appropriate dosage 1

Important Warnings

• Boxed warning: Increased mortality in elderly patients with dementia-related psychosis (not approved for this population)
• Boxed warning: Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients 1

Clinical Pearls

• Brexpiprazole has a unique pharmacological profile as a serotonin-dopamine activity modulator with partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors 4
• Compared to aripiprazole, brexpiprazole has less intrinsic activity at D2 receptors, potentially resulting in fewer activating side effects 4
• The medication can be taken once daily, simplifying the dosing regimen 5
• Titration is important to minimize side effects and optimize tolerability 1

Remember to periodically reassess the continued need for treatment and adjust dosage based on clinical response and tolerability.