What is the recommended dosage and treatment protocol for Rexulti (brexpiprazole) in patients with schizophrenia or major depressive disorder?

Rexulti (Brexpiprazole) Dosing and Treatment Protocol

For schizophrenia, start brexpiprazole at 1 mg daily, increase to 2 mg on days 5-7, then titrate to a target dose of 2-4 mg daily; for major depressive disorder as adjunctive therapy, start at 0.5-1 mg daily and titrate to a target of 2 mg daily (maximum 3 mg). 1

Schizophrenia Treatment Protocol

Initial Dosing

• Begin at 1 mg once daily 1, 2
• Increase to 2 mg daily on Day 5 to Day 7 1, 2
• Further titrate to 4 mg daily on Day 8 if needed 1, 2
• Target maintenance dose: 2-4 mg once daily 1, 3
• Maximum dose: 4 mg daily 1

Treatment Duration and Assessment

• Assess efficacy after 4 weeks at therapeutic dose before determining treatment failure 4
• If inadequate response after 4 weeks with confirmed adherence, switch to an alternative antipsychotic with different pharmacodynamic profile 4
• For maintenance therapy, continue long-term treatment to prevent relapse, as 65% of patients relapse within 1 year without medication 4

Efficacy Data

• Response rate: 45.5% vs 31% for placebo (NNT = 7) 3
• Relapse prevention: 13.5% relapsed on brexpiprazole vs 38.5% on placebo (NNT = 4) 3

Major Depressive Disorder (Adjunctive Therapy)

Initial Dosing

• Start at 0.5 mg or 1 mg once daily 1
• Target dose: 2 mg daily 1, 5
• Maximum dose: 3 mg daily 1
• Titrate gradually based on response and tolerability 1

Efficacy Data

• Response rate: 23.2% vs 14.5% for placebo (NNT = 12) 3
• Lower discontinuation rates due to adverse events compared to schizophrenia trials 3

Administration Details

General Instructions

• Administer once daily with or without food 1
• No food restrictions affect absorption 1

Dose Adjustments for Special Populations

Hepatic Impairment

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

Renal Impairment

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

CYP2D6 Poor Metabolizers

• Administer half the usual dose 1
• When combined with strong/moderate CYP3A4 inhibitors: Administer one-quarter of usual dose 1

Drug Interactions

• Strong CYP2D6 or CYP3A4 inhibitors: Reduce dose by half 1
• Strong CYP2D6 AND strong CYP3A4 inhibitors: Reduce dose to one-quarter 1
• Strong CYP3A4 inducers: Double the dose and adjust based on clinical response 1
• Note: For MDD patients on strong CYP2D6 inhibitors (paroxetine, fluoxetine), no dose adjustment needed 1

Adverse Effects Profile

Common Adverse Events

• Schizophrenia: Weight gain is the most common (≥4% and twice placebo rate) 1
• MDD: Weight gain, somnolence, and akathisia (≥5% and twice placebo rate) 1
• Akathisia rates: 5.5% vs 4.6% placebo in schizophrenia (NNH = 112); 8.6% in MDD trials (NNH = 15) 3, 5

Weight and Metabolic Effects

• Short-term: 10% of patients gained ≥7% body weight vs 4% placebo (NNH = 17) 2
• More prominent weight gain than aripiprazole or cariprazine, but less sedation than aripiprazole 5
• Minimal effects on glucose and lipids 2, 3
• Minimal prolactin elevation 2, 3

Monitoring Requirements

Baseline Assessment

• BMI, waist circumference, blood pressure 4
• HbA1c, fasting glucose, lipid panel 4
• Prolactin, liver function tests, renal function, complete blood count 4
• Electrocardiogram 4

Follow-up Monitoring

• Fasting glucose at 4 weeks 4
• BMI, waist circumference, blood pressure weekly for 6 weeks 4
• Repeat all baseline measures at 3 months, then annually 4
• Monitor for extrapyramidal symptoms to encourage adherence 6

Clinical Considerations

Pharmacological Profile

• Partial agonist at D2 and 5-HT1A receptors 2, 7
• Antagonist at 5-HT2A, alpha1B, and alpha2C receptors 2
• Lower intrinsic activity at D2 receptors compared to aripiprazole, suggesting better akathisia profile 2, 5

Treatment Positioning

• Consider as second-line option after failed trial with D2 partial agonist in schizophrenia 4
• For MDD, use as adjunctive therapy when antidepressant monotherapy inadequate 1, 3

Important Warnings

• Black Box Warning: Increased mortality in elderly with dementia-related psychosis (not approved for this indication) 1
• Black Box Warning: Increased suicidal thoughts in pediatric/young adult patients with MDD (not approved in pediatric MDD) 1
• Monitor for neuroleptic malignant syndrome, tardive dyskinesia, and metabolic changes 1
• Screen for pathological gambling and compulsive behaviors; consider dose reduction if occurs 1

Contraindications

• Known hypersensitivity to brexpiprazole or any component 1