Recommended Dosage and Treatment Protocol for Vraylar (Cariprazine) in Schizophrenia and Bipolar Disorder
For schizophrenia, Vraylar should be started at 1.5 mg once daily, titrated to 3 mg on day 2, with a recommended dosage range of 1.5-6 mg once daily; for bipolar disorder, start at 1.5 mg once daily, increase to 3 mg on day 2 for mania/mixed episodes (range 3-6 mg daily), or maintain at 1.5 mg with possible increase to 3 mg on day 15 for bipolar depression (maximum 3 mg daily). 1
Dosing Protocol for Schizophrenia
- Starting dose: 1.5 mg orally once daily
- Day 2: Can increase to 3 mg once daily
- Subsequent adjustments: Can be made in 1.5 mg or 3 mg increments based on clinical response and tolerability
- Recommended range: 1.5-6 mg once daily
- Maximum dose: 6 mg once daily (doses above 6 mg do not provide additional benefit but increase side effects) 1
Dosing Protocol for Bipolar I Disorder
For Manic or Mixed Episodes:
- Starting dose: 1.5 mg orally once daily
- Day 2: Increase to 3 mg once daily
- Recommended range: 3-6 mg once daily
- Subsequent adjustments: Can be made in 1.5 mg or 3 mg increments
- Maximum dose: 6 mg once daily 1
For Depressive Episodes (Bipolar Depression):
- Starting dose: 1.5 mg orally once daily
- Day 15: Can increase to 3 mg once daily based on response and tolerability
- Maximum dose: 3 mg once daily 1
Administration Guidelines
- Vraylar can be taken with or without food
- Administer once daily
- Due to the long half-life of cariprazine and its active metabolites (particularly didesmethyl-cariprazine), changes in dose will not be fully reflected in plasma for several weeks 1, 2
- Patients should be monitored for adverse reactions and treatment response for several weeks after starting Vraylar and after each dosage change 1
Dosage Modifications
For Patients Taking CYP3A4 Inhibitors:
With strong CYP3A4 inhibitors:
- Schizophrenia: Start at 1.5 mg every 3 days
- Bipolar disorder: 1.5 mg every 3 days 1
With moderate CYP3A4 inhibitors:
- Schizophrenia: Start at 1.5 mg every other day
- Bipolar disorder: 1.5 mg every other day 1
Monitoring Protocol
- Initial assessment: Evaluate baseline weight, BMI, blood pressure, fasting glucose, and lipid profile 3
- Regular monitoring:
- Long-term monitoring: Reassess dosage needs depending on stage of illness; higher doses may be required during acute phases, with lower doses during residual phases 5
Treatment Duration and Efficacy Assessment
- Initial efficacy assessment: After 4 weeks of treatment at therapeutic dose 5
- Inadequate response: If significant symptoms persist after 4 weeks at therapeutic dose, consider switching to an alternative antipsychotic 5
- Long-term treatment: Generally required for schizophrenia; attempt to find the lowest effective dose 3
Common Side Effects and Management
Most common adverse events (≥5% and at least twice rate of placebo):
Weight and metabolic effects:
Special Considerations
- Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist, which differentiates it from other antipsychotics 2
- The active metabolite didesmethyl-cariprazine (DDCAR) has a half-life of 1-3 weeks and becomes the predominant circulating moiety at steady state 7
- Due to this long half-life, steady state may not be reached for several weeks, requiring careful monitoring during dose adjustments 1
- Effective contraception is required if prescribed to female patients of childbearing age 5
Clinical Pearls
- Cariprazine may be particularly useful for patients with predominant negative symptoms in schizophrenia 5
- For bipolar depression, response rates (≥50% reduction in MADRS) for approved doses (1.5 and 3.0 mg/d) are 46.3% vs 35.9% for placebo (NNT 10) 7
- The 3.0 mg/d dose has higher rates of adverse events than the 1.5 mg/d dose in bipolar depression 7
- Cariprazine has not been established as safe and effective in pediatric patients, though pharmacokinetic parameters in adolescents appear consistent with those in adults 8