What is the recommended dosage of Rexulti (brexpiprazole)?

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Last updated: October 22, 2025View editorial policy

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Recommended Dosage of Rexulti (Brexpiprazole)

For the treatment of schizophrenia in adults, the recommended starting dose of Rexulti is 1 mg once daily for days 1-4, then 2 mg once daily for days 5-7, with a target dose range of 2-4 mg once daily. 1

Dosage Guidelines for Different Indications

Schizophrenia

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

Major Depressive Disorder (Adjunctive Treatment)

  • Start with 0.5 mg or 1 mg once daily 1
  • Titrate to 1 mg once daily, then to target dose of 2 mg once daily based on clinical response and tolerability (increase at weekly intervals) 1
  • Maximum recommended daily dosage is 3 mg 1

Dosage Adjustments for Special Populations

Hepatic Impairment

  • For 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

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

Drug Interactions and Dosage Modifications

Patients Taking CYP Inhibitors

  • Strong CYP2D6 inhibitors: Administer half of the recommended dosage 1
  • Strong CYP3A4 inhibitors: Administer half of the recommended dosage 1
  • Strong/moderate CYP2D6 inhibitors with strong/moderate CYP3A4 inhibitors: Administer a quarter of the recommended dosage 1

Patients Taking CYP3A4 Inducers

  • Double the recommended dosage over 1-2 weeks 1
  • If the CYP3A4 inducer is discontinued, reduce the brexpiprazole dosage to the original level over 1-2 weeks 1

Administration

  • Brexpiprazole can be taken once daily with or without food 1
  • Periodic reassessment is recommended to determine continued need and appropriate dosage for treatment 1

Clinical Considerations

Efficacy

  • In clinical trials for schizophrenia, the response rate was 45.5% vs. 31.0% for placebo, with a Number Needed to Treat (NNT) of 7 2
  • For maintenance treatment, brexpiprazole significantly delayed time to relapse compared with placebo 3
  • For adjunctive treatment of MDD, the response rate was 23.2% vs. 14.5% for placebo, with an NNT of 12 2

Safety and Tolerability

  • Generally well tolerated with relatively low incidence of activating and sedating adverse effects 3
  • Most common adverse effects include akathisia (5.5% in schizophrenia trials, 8.6% in MDD trials), headache, and gastrointestinal effects 2
  • Moderate weight gain may occur, with more significant weight gain (≥7% of body weight) observed in longer-term studies 2
  • Effects on glucose, lipids, and prolactin are generally small 2

Important Warnings

  • Black box warning for increased mortality in elderly patients with dementia-related psychosis 1
  • Black box warning for increased risk of suicidal thoughts and behaviors in pediatric patients and young adults 1
  • Monitor patients closely for clinical worsening and emergence of suicidal thoughts and behaviors 1

Practical Tips

  • Titration to target dose is essential to minimize side effects 4
  • Once-daily dosing is effective and may improve adherence 4
  • For patients experiencing side effects, consider slower titration or dose reduction within the recommended range 2

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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