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

Recommended Use and Dosage of Rexulti (Brexpiprazole)

Brexpiprazole (Rexulti) is indicated for the treatment of schizophrenia in adults (recommended dose 2-4 mg once daily) and as adjunctive therapy for major depressive disorder (MDD) in adults (recommended dose 2 mg once daily). 1

Indications and Dosing

Schizophrenia Treatment

• Starting dose: 1 mg once daily on days 1-4
• Titration: Increase to 2 mg once daily on days 5-7
• Target dose: 2-4 mg once daily (can increase to 4 mg on day 8 based on clinical response)
• Maximum dose: 4 mg once daily 1

Adjunctive Treatment for Major Depressive Disorder

• Starting dose: 0.5 mg or 1 mg once daily
• Titration: Increase to 1 mg once daily, then to target dose at weekly intervals
• Target dose: 2 mg once daily
• Maximum dose: 3 mg once daily 1

Administration

• Take once daily with or without food
• Periodic reassessment is recommended to determine continued need and appropriate dosage 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

• Creatinine clearance <60 mL/min:
  • 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 CYP3A4 inducers: Double the recommended dosage over 1-2 weeks
• Combined CYP2D6 inhibitors and CYP3A4 inhibitors: Administer quarter of recommended dosage 1

Efficacy

• Schizophrenia: Pooled responder rates of 45.5% vs 31% for placebo (NNT of 7)
• Relapse prevention: 13.5% relapse rate vs 38.5% for placebo (NNT of 4)
• MDD (adjunctive): Response rates of 23.2% vs 14.5% for placebo (NNT of 12) 2

Adverse Effects

Common Adverse Effects

• Weight gain: Most common adverse effect (≥4% and at least twice the rate of placebo) 3
  • Approximately 10% of patients gain ≥7% body weight (vs 4% on placebo)
• Akathisia: 5.5% in schizophrenia trials, 8.6% in MDD trials 2
• Other common effects: headache, somnolence, gastrointestinal effects 3, 4

Monitoring

• Baseline and periodic monitoring:
  • Weight and metabolic parameters
  • Blood pressure and heart rate (risk of orthostatic hypotension)
  • Mental status for emergence of suicidal thoughts (especially in MDD patients)
  • Extrapyramidal symptoms 1

Contraindications and Warnings

• Boxed warning: Increased mortality in elderly patients with dementia-related psychosis (not approved for this indication)
• Boxed warning: Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients 1
• Known hypersensitivity to brexpiprazole or any components 1

Pharmacology

• Brexpiprazole is a serotonin-dopamine activity modulator that acts as:
  • Partial agonist at dopamine D2 and serotonin 5-HT1A receptors
  • Antagonist at serotonin 5-HT2A, adrenergic alpha1B and alpha2C receptors 3
• Compared to aripiprazole, brexpiprazole has:
  • More potent activity at 5-HT1A receptors
  • Less intrinsic activity at D2 receptors
  • Potentially lower risk of akathisia and extrapyramidal symptoms 3, 4

Clinical Pearls

• Brexpiprazole has a long half-life (52-92 hours), allowing for once-daily dosing 5
• Steady state is reached after approximately 10 days of treatment 5
• Dose adjustments are not required for CYP2D6 inhibitors in MDD patients as this was accounted for in clinical trials 1
• Monitor for weight gain, which may be more prominent than with some other antipsychotics 4
• Effects on glucose, lipids, and prolactin appear minimal in clinical trials 2

Brexpiprazole represents an important treatment option with a unique pharmacological profile that may offer advantages in terms of tolerability compared to some other antipsychotic medications, particularly regarding akathisia and extrapyramidal symptoms.