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

Recommended Use and Dosage of Rexulti (Brexpiprazole)

Rexulti (brexpiprazole) is indicated for the treatment of schizophrenia in adults (1-4 mg/day) and as adjunctive therapy for major depressive disorder (0.5-3 mg/day), with specific dosing recommendations based on indication, hepatic/renal function, and CYP2D6 metabolizer status. 1

Indications and Starting Dosage

For Schizophrenia (Adults):

• 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 1

For Major Depressive Disorder (Adults) - 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 (at weekly intervals)
• Maximum dose: 3 mg once daily 1

Administration

• Take once daily with or without food 1
• Periodically reassess to determine continued need and appropriate dosage 1

Dosage Adjustments for 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:

• Administer half of the recommended dosage 1
• For known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors: Administer quarter of the recommended dosage 1

Drug Interactions

Dosage Modifications:

• Strong CYP2D6 inhibitors: Administer half of recommended dosage (except in MDD where no adjustment needed) 1
• Strong CYP3A4 inhibitors: Administer half of recommended dosage 1
• Combined strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors: Administer quarter of recommended dosage 1
• Strong CYP3A4 inducers: Double the recommended dosage over 1-2 weeks 1

Efficacy

Schizophrenia:

• Pooled responder rates: 46% for brexpiprazole 2-4 mg/day vs. 31% for placebo (NNT = 7) 2
• In maintenance treatment, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%, NNT = 4) 2

Major Depressive Disorder:

• As adjunctive therapy: NNT = 12 for response and 17-31 for remission vs. placebo 3

Common Adverse Effects

Most Common Side Effects:

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

Other Notable Adverse Effects:

• Akathisia: Rates of 5.5% for brexpiprazole 1-4 mg/day vs. 4.6% for placebo (NNH = 112) 2
• Weight gain: Approximately 10% of patients on brexpiprazole 1-4 mg/day gained ≥7% body weight (vs. 4% on placebo, NNH = 17) 2
• Metabolic effects: Small effects on glucose and lipids 2
• Prolactin: Minimal effects 2
• QTc interval: No clinically relevant effects 2

Warnings and Precautions

• Boxed warning: Increased mortality in elderly patients with dementia-related psychosis; not approved for this indication 1
• Boxed warning: Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants 1
• Cerebrovascular adverse reactions in elderly patients with dementia-related psychosis 1
• Neuroleptic malignant syndrome: Requires immediate discontinuation and close monitoring 1
• Tardive dyskinesia: Consider discontinuation if clinically appropriate 1
• Metabolic changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain 1
• Pathological gambling and compulsive behaviors: Consider dose reduction or discontinuation 1
• Orthostatic hypotension and syncope: Monitor vital signs in at-risk patients 1

Clinical Pearls

• Brexpiprazole has less intrinsic activity at D2 receptors compared to aripiprazole, potentially resulting in lower rates of activating side effects like akathisia 4
• The pharmacological profile suggests a more tolerable side effect profile regarding akathisia, extrapyramidal symptoms, and sedation compared to some other antipsychotics 3
• When discontinuing or interrupting therapy for reasons other than hematologic toxicities, consider tapering the dose gradually to prevent symptom recurrence 1
• Regular monitoring of weight, metabolic parameters, and emergence of movement disorders is recommended

Remember that brexpiprazole represents a newer generation of antipsychotics with a unique receptor profile that may offer advantages in terms of tolerability for some patients, but direct head-to-head comparisons with other agents are still needed to fully establish its place in treatment algorithms 5.