Is Vraylar (cariprazine) used to treat bipolar 2 disorder?

Vraylar (Cariprazine) for Bipolar II Disorder Treatment

Vraylar (cariprazine) is not specifically FDA-approved for bipolar II disorder, though it may be considered as an off-label treatment option for bipolar II depression based on its efficacy in bipolar I depression. While cariprazine has demonstrated efficacy for both manic and depressive episodes in bipolar I disorder, the evidence specifically for bipolar II disorder is limited.

Approved Indications for Vraylar in Bipolar Disorder

Cariprazine has established FDA approval for:

• Acute manic and mixed episodes in bipolar I disorder
• Depressive episodes in bipolar I disorder 1

Mechanism and Pharmacological Properties

Cariprazine has unique pharmacological properties that may explain its efficacy across the bipolar spectrum:

• D3-preferring dopamine D2/D3 partial agonist with 10-fold higher affinity for D3 receptors 2
• Long half-life (1-3 weeks) for its active metabolite didesmethyl-cariprazine (DDCAR) 3
• May improve both anhedonia and cognitive dysfunction, which are prominent features in bipolar depression 4

Evidence for Bipolar Depression

For bipolar I depression:

• Cariprazine 1.5-3 mg/day has demonstrated efficacy as monotherapy 5
• Response rates (≥50% reduction in MADRS scores) were 46.3% vs 35.9% for placebo (NNT=10) 3
• Remission rates (MADRS ≤10) were 30.2% vs 20.9% for placebo (NNT=11) 3

Treatment Considerations for Bipolar II

The American Academy of Child and Adolescent Psychiatry guidelines suggest:

• Lamotrigine is a preferred mood stabilizer for bipolar II depression due to its efficacy and metabolically neutral profile 6
• Combination therapy with an atypical antipsychotic and mood stabilizer may be beneficial for managing both affective and psychotic symptoms 6

Dosing and Monitoring

If considering cariprazine for bipolar II depression:

• Lower doses (1.5-3 mg/day) appear most effective for bipolar depression 5, 3
• Regular monitoring should include:
  • Weight, BMI, blood pressure
  • Fasting glucose and lipid panel
  • Assessment for akathisia and extrapyramidal symptoms 6

Side Effect Profile

Common side effects of cariprazine include:

• Akathisia (most common adverse effect)
• Extrapyramidal symptoms
• Nausea
• Restlessness 3

Importantly, cariprazine appears to have a favorable metabolic profile compared to some other atypical antipsychotics 5.

Clinical Approach for Bipolar II Disorder

1. Consider first-line options with stronger evidence for bipolar II (lamotrigine)
2. For patients with prominent depressive symptoms not responding to first-line treatments, cariprazine may be considered as an off-label option
3. Start with lower doses (1.5 mg/day) and titrate slowly based on response and tolerability
4. Monitor closely for akathisia, which is the most common adverse effect leading to discontinuation

Important Caveats

• Direct studies specifically in bipolar II disorder populations are lacking
• The decision to use cariprazine off-label should be made after careful consideration of other evidence-based options
• Higher doses (3-12 mg/day) used for bipolar mania are likely inappropriate for bipolar II patients who do not experience full mania 5