What is Rexalti (brexpiprazole) used for and what are its dosing recommendations?

Rexulti (Brexpiprazole): Indications and Dosing

Rexulti (brexpiprazole) is FDA-approved for two indications: as adjunctive therapy to antidepressants for major depressive disorder (MDD) in adults, and as monotherapy for schizophrenia in adults. 1

Approved Indications

Brexpiprazole is indicated for:

• Adjunctive treatment of major depressive disorder (MDD) in adults who have had inadequate response to standard antidepressant therapy 1, 2
• Treatment of schizophrenia in adults as monotherapy 1, 2

Mechanism of Action

Brexpiprazole is a serotonin-dopamine activity modulator that acts as:

• Partial agonist at dopamine D2 and serotonin 5-HT1A receptors 3, 4
• Antagonist at serotonin 5-HT2A receptors 3, 4
• Antagonist at noradrenergic alpha-1B and alpha-2C receptors 3, 4

Compared to aripiprazole, brexpiprazole displays less intrinsic activity at D2 receptors and more potency at 5-HT1A receptors 3

Dosing Recommendations

For Major Depressive Disorder (Adjunctive Therapy)

• Starting dose: 0.5 mg or 1 mg once daily 1
• Target dose: 2 mg once daily 1, 5
• Maximum dose: 3 mg once daily 1
• Administration: Once daily with or without food 1

For Schizophrenia

• Starting dose: 1 mg once daily 1, 3
• Titration schedule: Increase to 2 mg on Day 5-7, then to 4 mg on Day 8 3
• Target dose range: 2-4 mg once daily 1, 3
• Maximum dose: 4 mg once daily 1
• Administration: Once daily with or without food 1

Dose Adjustments for Special Populations

Hepatic Impairment

• Moderate to severe hepatic impairment: Maximum 2 mg daily for MDD; maximum 3 mg daily for schizophrenia 1

Renal Impairment

• CrCl < 60 mL/minute: Maximum 2 mg daily for MDD; maximum 3 mg daily for schizophrenia 1

CYP2D6 Poor Metabolizers and Drug Interactions

• Strong CYP2D6 or CYP3A4 inhibitors: Administer half the recommended dosage 1
• Strong/moderate CYP2D6 with strong/moderate CYP3A4 inhibitors: Administer one-quarter of the recommended dosage 1
• CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors: Administer one-quarter of the recommended dosage 1
• Strong CYP3A4 inducers: Double the recommended dosage and adjust based on clinical response 1

Efficacy Data

Schizophrenia

• Pooled responder rates: 45.5% for brexpiprazole 2-4 mg/day vs. 31% for placebo (NNT = 7) 3, 5
• Relapse prevention at 52 weeks: 13.5% relapsed on brexpiprazole vs. 38.5% on placebo (NNT = 4) 3, 5

Major Depressive Disorder

• Pooled responder rates: 23.2% for brexpiprazole vs. 14.5% for placebo (NNT = 12) 5

Common Adverse Effects

Schizophrenia

• Most common adverse event (≥4% and twice placebo rate): Weight gain 1, 3
• Akathisia: 5.5% vs. 4.6% for placebo (NNH = 112) 3, 5
• Weight gain ≥7%: 10% of patients vs. 4% for placebo (NNH = 17) 3

Major Depressive Disorder

• Common adverse events (≥5% and twice placebo rate): Weight gain, somnolence, akathisia 1
• Akathisia: 8.6% (NNH = 15) 5
• Discontinuation due to adverse events: 3% vs. 1% for placebo (NNH = 53) 5

Critical Safety Warnings

Boxed Warning: Brexpiprazole carries two black box warnings 1:

1. Increased mortality in elderly patients with dementia-related psychosis - brexpiprazole is NOT approved for this indication 1
2. Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients - close monitoring required for all antidepressant-treated patients 1

Other Important Warnings

• Cerebrovascular adverse reactions in elderly patients with dementia 1
• Neuroleptic malignant syndrome: Requires immediate discontinuation 1
• Tardive dyskinesia: Consider discontinuation if clinically appropriate 1
• Metabolic changes: Monitor for hyperglycemia, diabetes, dyslipidemia, and weight gain 1
• Pathological gambling and compulsive behaviors: Consider dose reduction or discontinuation 1
• Orthostatic hypotension and syncope: Monitor blood pressure in at-risk patients 1

Contraindications

Known hypersensitivity to brexpiprazole or any component of the formulation 1