What is the recommended dosage and treatment guidelines for Rexulti (brexpiprazole)?

Recommended Dosage and Treatment Guidelines for Rexulti (Brexpiprazole)

For the treatment of schizophrenia and as adjunctive therapy for major depressive disorder (MDD), the recommended dosage of Rexulti (brexpiprazole) varies by indication, with specific titration schedules required to optimize efficacy and minimize side effects.

Dosage Recommendations by Indication

For Schizophrenia in Adults:

• Start with 1 mg once daily for days 1-4 1
• Increase to 2 mg once daily on days 5-7 1
• On day 8, may increase to a maximum of 4 mg once daily based on clinical response and tolerability 1
• The recommended target dosage range is 2-4 mg once daily 1, 2

For Adjunctive Treatment of Major Depressive Disorder (MDD) in Adults:

• Start with 0.5 mg or 1 mg once daily 1
• Titrate to 1 mg once daily, then to the target dosage of 2 mg once daily (increase at weekly intervals based on clinical response and tolerability) 1
• The maximum recommended daily dosage is 3 mg 1, 3
• Periodically reassess to determine continued need and appropriate dosage 1

Administration Guidelines

• Administer orally once daily with or without food 1
• For optimal tolerability, follow the recommended titration schedule for each indication 1, 2
• Medication should be taken at the same time each day to maintain consistent blood levels 2

Special Population Considerations

Hepatic Impairment:

• For patients with moderate to severe hepatic impairment (Child-Pugh score ≥7): 1
  • Maximum 2 mg once daily for MDD
  • Maximum 3 mg once daily for schizophrenia

Renal Impairment:

• For patients with creatinine clearance <60 mL/minute: 1
  • Maximum 2 mg once daily for MDD
  • Maximum 3 mg once daily for schizophrenia

CYP2D6 Poor Metabolizers and Drug Interactions:

• For known CYP2D6 poor metabolizers: administer half of the recommended dosage 1
• For patients taking strong CYP3A4 inhibitors: administer half of the recommended dosage 1
• For patients taking strong CYP3A4 inducers: double the recommended dosage over 1-2 weeks 1
• For patients taking both strong/moderate CYP2D6 inhibitors and strong/moderate CYP3A4 inhibitors: administer a quarter of the recommended dosage 1
• Note: In MDD studies, dosage was not adjusted for strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine), so brexpiprazole may be administered without dosage adjustment in MDD patients taking these medications 1

Efficacy and Clinical Outcomes

• In schizophrenia trials, pooled responder rates were 46% for brexpiprazole 2-4 mg/day vs. 31% for placebo (NNT of 7) 2, 4
• In a 52-week maintenance study, significantly fewer patients relapsed with brexpiprazole compared to placebo (13.5% vs. 38.5%, NNT of 4) 2, 4
• As adjunctive therapy in MDD, response rates were 23.2% for brexpiprazole vs. 14.5% for placebo (NNT of 12) 4, 3

Common Adverse Effects and Monitoring

• Most common adverse effects include: 2, 4

  • Weight gain (most common adverse event with incidence ≥4% and at least twice the rate of placebo)
  • Akathisia (5.5% in schizophrenia trials, 8.6% in MDD trials)
  • Somnolence

• Monitor for: 1, 2

  • Weight gain (approximately 10% of patients gained ≥7% body weight in short-term trials)
  • Metabolic changes (effects on glucose and lipids are generally small)
  • Akathisia and extrapyramidal symptoms
  • Orthostatic hypotension and syncope

Important Warnings and Contraindications

• Contraindicated in patients with known hypersensitivity to brexpiprazole or any of its components 1
• Not approved for treatment of dementia-related psychosis due to increased mortality risk in elderly patients 1
• Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients when used as an antidepressant 1
• Use caution in patients with cardiovascular or cerebrovascular disease due to risk of orthostatic hypotension 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 2, 5
• Compared to aripiprazole, brexpiprazole has less intrinsic activity at D2 receptors, potentially resulting in fewer activation-like adverse effects 5, 3
• The gradual titration schedule is designed to minimize side effects, particularly akathisia 2, 6
• Once-daily dosing enhances convenience and may improve adherence 2, 6

Remember that individual response to brexpiprazole may vary, and close monitoring during initiation and dose adjustments is essential to optimize outcomes and minimize adverse effects.