What is Rexulti (brexpiprazole) used for?

Rexulti (Brexpiprazole) Indications

Rexulti (brexpiprazole) is FDA-approved for the treatment of schizophrenia in adults and as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults. 1

Primary Indications

Brexpiprazole is a third-generation atypical antipsychotic that serves two main therapeutic purposes:

1. Treatment of Schizophrenia

   • Used as monotherapy for adults with schizophrenia
   • Effective for reducing positive symptoms of psychosis
   • Helps prevent relapse in maintenance treatment

2. Adjunctive Treatment for Major Depression

   • Added to antidepressant therapy when patients show inadequate response to antidepressant treatment alone
   • Not indicated as a first-line treatment for depression

Pharmacological Profile

Brexpiprazole works as a serotonin-dopamine activity modulator with a unique receptor binding profile:

• Partial agonist at dopamine D2 receptors (with less intrinsic activity than aripiprazole) 2
• Partial agonist at serotonin 5-HT1A receptors
• Antagonist at 5-HT2A receptors
• Antagonist at noradrenergic α1B and α2C receptors 3

This receptor profile contributes to its therapeutic effects while potentially offering a more favorable side effect profile compared to some other antipsychotics.

Efficacy

For Schizophrenia:

• Response rates of approximately 45.5% vs. 31.0% for placebo (NNT of 7) 4
• Significantly fewer relapses in maintenance treatment compared to placebo (13.5% vs. 38.5%, NNT of 4) 4
• Recommended dose: 2-4 mg/day 1

For Major Depressive Disorder:

• Response rates of 23.2% vs. 14.5% for placebo when added to antidepressants (NNT of 12) 4
• Recommended dose: 2 mg/day as adjunctive therapy 1

Safety and Tolerability

Brexpiprazole has a generally favorable side effect profile:

• Common adverse effects:

  • Akathisia (5.5% in schizophrenia trials, 8.6% in MDD trials) 4
  • Gastrointestinal side effects 5
  • Moderate weight gain 2

• Advantages compared to some other antipsychotics:

  • Lower rates of akathisia compared to aripiprazole and cariprazine 2
  • Less sedation than aripiprazole 2
  • Minimal effects on prolactin levels 4
  • No clinically relevant effects on ECG QT interval 4

Dosing Considerations

• Schizophrenia: Target dose of 2-4 mg once daily 2
• MDD adjunctive therapy: Target dose of 2 mg once daily 2
• Requires titration over 1-2 weeks to reach target dose 5
• Dose adjustments needed for:
  • Hepatic or renal dysfunction
  • Poor CYP2D6 metabolizers 2

Clinical Pearls and Caveats

• Brexpiprazole is not indicated for the treatment of patients with dementia-related psychosis
• It should be titrated gradually to minimize side effects
• As with other antipsychotics, metabolic monitoring is recommended
• While brexpiprazole has shown efficacy in clinical trials, real-world comparative effectiveness data with other antipsychotics is still limited 5
• The drug reaches steady state after approximately 10 days of treatment 6

Brexpiprazole represents an important option in the antipsychotic armamentarium, with its dual indications for schizophrenia and as adjunctive therapy for MDD providing clinicians with a versatile treatment option that may be particularly useful for patients who cannot tolerate other antipsychotic medications.