Indications for Vraylar (Cariprazine)
Vraylar (cariprazine) is FDA-approved for the treatment of schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults, and as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults. 1
FDA-Approved Indications
Vraylar is an atypical antipsychotic with the following specific indications:
Schizophrenia in adults
- Recommended dose: 1.5-6 mg daily
- Starting dose: 1.5 mg daily
Bipolar I disorder (manic or mixed episodes)
- Recommended dose: 3-6 mg daily
- Starting dose: 1.5 mg daily
Bipolar I disorder (depressive episodes)
- Recommended dose: 1.5-3 mg daily
- Starting dose: 1.5 mg daily
Adjunctive therapy for Major Depressive Disorder (MDD)
- Recommended dose: 1.5-3 mg daily
- Starting dose: 1.5 mg daily
Pharmacological Properties
Vraylar has a unique pharmacological profile that distinguishes it from other antipsychotics:
- Acts as a dopamine D3 and D2 receptor partial agonist with a 10-fold higher affinity for D3 receptors than D2 receptors 2
- Partial agonist activity at serotonin 5-HT1A receptors
- Antagonist activity at 5-HT2B and 5-HT2A receptors 3
- Long half-life through its active metabolite didesmethyl-cariprazine (DDCAR), which has a half-life of 1-3 weeks 2
Clinical Efficacy
Schizophrenia
- Demonstrated superiority over placebo in three 6-week randomized controlled trials
- Pooled responder rates: 31% for cariprazine 1.5-6 mg/day vs. 21% for placebo 3
- Particularly effective for negative symptoms, which are typically difficult to treat with other antipsychotics 4
Bipolar Mania
- Effective for acute manic or mixed episodes
- Common adverse events include extrapyramidal symptoms, akathisia, dyspepsia, vomiting, somnolence, and restlessness 1
Bipolar Depression
- Response rates (≥50% reduction in MADRS score): 46.3% for cariprazine 1.5-3 mg/day vs. 35.9% for placebo
- Remission rates (MADRS score ≤10): 30.2% for cariprazine vs. 20.9% for placebo 2
Adjunctive Treatment for MDD
- Most recent FDA-approved indication
- Effective as an add-on therapy to antidepressants for patients with inadequate response to antidepressant monotherapy 1
Important Monitoring Considerations
When prescribing Vraylar, clinicians should:
- Monitor for extrapyramidal symptoms and akathisia, which are the most common adverse effects 1
- Be aware of the long half-life of the active metabolite, which means that adverse effects may appear or persist for several weeks after discontinuation 1
- Monitor for metabolic changes, although weight gain appears to be less significant than with some other antipsychotics 3
- Perform baseline and follow-up laboratory monitoring including complete blood counts, as recommended for antipsychotic medications 5
- Be vigilant for suicidal thoughts in young adults under 24 years of age 6
Special Warnings and Precautions
- Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis (Vraylar is not approved for this population) 1
- Black Box Warning: Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients 1
- Cariprazine is not approved for use in pediatric patients 1
- Due to its long half-life, adverse reactions may appear or persist for several weeks after discontinuation 1
Dosing Considerations
- Administer once daily with or without food
- Dose adjustments are required with strong CYP3A4 inhibitors
- Concomitant use with CYP3A4 inducers is not recommended 1
- Slow titration is recommended to minimize side effects, particularly in young adults 6
Vraylar represents an important treatment option for multiple psychiatric conditions, with its unique receptor profile potentially offering advantages for treating negative symptoms in schizophrenia and for patients with bipolar depression.