Is Rexulti (brexpiprazole) effective for treating hypomania or mania?

Rexulti (Brexpiprazole) for Hypomania/Mania Treatment

Rexulti (brexpiprazole) is not recommended as a first-line treatment for hypomania or mania, as it is not FDA-approved for bipolar disorder and lacks specific evidence for efficacy in manic episodes. 1

Treatment Recommendations for Hypomania/Mania

First-Line Treatment Options

• For acute mania or hypomania in bipolar disorder, FDA-approved medications should be used as first-line treatments 1:
  • Lithium (approved down to age 12 for acute mania and maintenance therapy)
  • Aripiprazole, valproate, olanzapine, risperidone, quetiapine, and ziprasidone (approved for acute mania in adults)

Evidence for Atypical Antipsychotics in Mania/Hypomania

• Atypical antipsychotics with the strongest evidence for efficacy in acute mixed mania/hypomania include aripiprazole, asenapine, olanzapine, and ziprasidone 2
• Quetiapine and divalproex/valproate are also efficacious for treating mixed states 2
• Risperidone has shown efficacy in an open-label study for hypomania in bipolar II disorder, suggesting potential benefit 3

Brexpiprazole (Rexulti) Considerations

• Brexpiprazole is currently only FDA-approved for schizophrenia and as adjunctive therapy for major depressive disorder 4, 5
• Like aripiprazole, brexpiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors 4
• Brexpiprazole displays less intrinsic activity at D2 receptors compared to aripiprazole, which may result in lower propensity for activating adverse events 4
• No specific clinical trials have evaluated brexpiprazole for bipolar mania or hypomania

Treatment Algorithm for Hypomania/Mania

1. Initial Assessment: Determine if the presentation is bipolar I mania, bipolar II hypomania, or mixed features 1

2. First-Line Treatment:

   • For well-defined bipolar I mania: Lithium, valproate, or an FDA-approved atypical antipsychotic (aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone) 1
   • For hypomania: Similar approach but may use lower doses 3

3. Combination Therapy:

   • For severe cases or inadequate response to monotherapy, consider combinations of atypical antipsychotics with mood stabilizers 2

4. Treatment-Resistant Cases:

   • Consider alternative agents or combinations not used in first-line treatment
   • For severely impaired adolescents with manic episodes unresponsive to medications, ECT may be considered 1

Monitoring and Safety Considerations

• For atypical antipsychotics, monitor for:

  • Weight gain and metabolic issues (diabetes, hyperlipidemia) 1
  • Baseline and follow-up assessments of BMI, waist circumference, blood pressure, fasting glucose, and lipid panel 1
  • Extrapyramidal symptoms and tardive dyskinesia 1

• Caution with antidepressants in bipolar disorder:

  • Antidepressants may destabilize mood or trigger manic episodes 1
  • SSRIs should be avoided in patients with bipolar disorder due to risk of mania 1

Clinical Caveat

While brexpiprazole shares some pharmacological properties with aripiprazole (which is FDA-approved for mania), it cannot be automatically assumed to have the same clinical efficacy for hypomania or mania without specific clinical trial evidence. If considering off-label use of brexpiprazole, it would be more appropriate after failure of established treatments with proven efficacy for mania/hypomania 1, 4.