Vraylar (Cariprazine) Dosing for Schizophrenia and Bipolar Disorder
For schizophrenia, start Vraylar at 1.5 mg once daily and titrate to a target range of 1.5-6 mg daily; for bipolar mania, start at 1.5 mg and increase to 3 mg on Day 2 with a target range of 3-6 mg daily; for bipolar depression, start at 1.5 mg daily with a maximum of 3 mg daily. 1
Schizophrenia Dosing
Starting dose: 1.5 mg orally once daily 1
Titration schedule:
- May increase to 3 mg on Day 2 1
- Further adjustments can be made in 1.5 mg or 3 mg increments based on clinical response and tolerability 1
Target dose range: 1.5-6 mg once daily 1
Maximum dose: 6 mg once daily—doses above 6 mg daily do not provide increased effectiveness sufficient to outweigh dose-related adverse reactions 1
The 2025 INTEGRATE guidelines support cariprazine as a suitable option for switching in cases of persistent negative symptoms when positive symptoms are well controlled 2
Bipolar I Disorder - Manic or Mixed Episodes
Starting dose: 1.5 mg orally once daily 1
Titration schedule:
- Increase to 3 mg once daily on Day 2 1
- Further adjustments can be made in 1.5 mg or 3 mg increments based on response and tolerability 1
Target dose range: 3-6 mg once daily 1
Maximum dose: 6 mg once daily—doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions 1
Bipolar I Disorder - Depressive Episodes
Starting dose: 1.5 mg orally once daily 1
Titration schedule:
- May increase to 3 mg once daily on Day 15 based on clinical response and tolerability 1
Target dose range: 1.5-3 mg once daily 1
Maximum dose: 3 mg once daily 1
Administration Guidelines
Timing: Once daily, can be taken with or without food 1
Critical pharmacokinetic consideration: Due to the long half-life of cariprazine (2-5 days) and its active metabolite didesmethyl-cariprazine (2-3 weeks), changes in dose will not be fully reflected in plasma for several weeks 3, 1, 4, 5
Monitoring requirement: Prescribers must monitor patients for adverse reactions and treatment response for several weeks after starting Vraylar and after each dosage change 1
Dose Modifications with CYP3A4 Inhibitors
When Starting Vraylar While Taking CYP3A4 Inhibitors:
Strong CYP3A4 inhibitors:
- For schizophrenia: Start at 1.5 mg every 3 days; may increase to 1.5 mg every other day if needed 1
- For bipolar mania, bipolar depression: 1.5 mg every 3 days 1
Moderate CYP3A4 inhibitors:
- For schizophrenia: Start at 1.5 mg every other day; may increase to 1.5 mg daily if needed 1
- For bipolar mania, bipolar depression: 1.5 mg every other day 1
When Adding CYP3A4 Inhibitors to Stable Vraylar Dose:
If currently on 1.5 or 3 mg daily:
- With strong inhibitor: Reduce to 1.5 mg every 3 days 1
- With moderate inhibitor: Reduce to 1.5 mg every other day 1
If currently on 4.5 or 6 mg daily:
- With strong inhibitor: Reduce to 1.5 mg every other day 1
- With moderate inhibitor: Reduce to 1.5 mg daily 1
Safety and Tolerability Profile
Common adverse events (≥10% in long-term studies): akathisia, insomnia, weight increase, and headache 6
Extrapyramidal symptoms: Akathisia, tremor, restlessness, and extrapyramidal disorder occurred in ≥5% of patients in long-term studies 6
Metabolic effects: Cariprazine does not appear to adversely impact metabolic variables, with mean decreases in total cholesterol (-5.3 mg/dL), LDL (-3.5 mg/dL), and HDL (-0.8 mg/dL) observed 6
Weight changes: Mean weight increase of 1.58 kg in long-term studies; 27% experienced ≥7% weight increase while 11% experienced ≥7% weight decrease 6
Prolactin: Mean prolactin levels decreased by 15.4 ng/mL across all dose groups 6
Cardiovascular: No clinically significant changes in blood pressure, pulse, or QT interval 7, 6
Special Populations
Women of childbearing age: The American College of Psychiatry recommends effective contraception when taking cariprazine 3