Vraylar (Cariprazine) Dosage and Use for Schizophrenia and Bipolar Disorder
Vraylar (cariprazine) is an atypical antipsychotic with FDA approval for schizophrenia (1.5-6 mg daily) and bipolar disorder (3-6 mg daily for mania, 1.5-3 mg daily for depression), administered once daily with or without food. 1
Mechanism of Action
Vraylar is a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, distinguishing it from other antipsychotics. It also acts as:
- Partial agonist at serotonin 5-HT1A receptors
- Antagonist at 5-HT2B and 5-HT2A receptors 2
This unique receptor profile contributes to its efficacy in both schizophrenia and bipolar disorder.
Dosing Guidelines
Schizophrenia
- Starting dose: 1.5 mg once daily
- Recommended range: 1.5-6 mg once daily
- Day 2: Can increase to 3 mg
- Further adjustments: In 1.5 mg or 3 mg increments
- Maximum dose: 6 mg daily 1
Bipolar I Disorder - Manic/Mixed Episodes
- Starting dose: 1.5 mg once daily
- Day 2: Increase to 3 mg once daily
- Recommended range: 3-6 mg once daily
- Further adjustments: In 1.5 mg or 3 mg increments
- Maximum dose: 6 mg daily 1
Bipolar I Disorder - Depression
- Starting dose: 1.5 mg once daily
- Day 15: Can increase to 3 mg once daily if needed
- Maximum dose: 3 mg daily 1
Major Depressive Disorder (Adjunctive Therapy)
- Starting dose: 1.5 mg once daily
- Day 15: Can increase to 3 mg once daily if needed
- Maximum dose: 3 mg daily 1
Important Pharmacokinetic Considerations
Vraylar has a uniquely long half-life compared to other antipsychotics:
- Parent compound half-life: 2-5 days
- Active metabolite (didesmethyl-cariprazine) half-life: 2-3 weeks 3
This extended half-life means:
- Changes in dose will not be fully reflected in plasma for several weeks
- Patients should be monitored for adverse reactions and treatment response for several weeks after starting or changing doses 1
- Steady state may not be reached for 2-3 weeks 3
Dosage Adjustments
CYP3A4 Inhibitors
When taking Vraylar with CYP3A4 inhibitors, dose adjustments are required:
Strong CYP3A4 Inhibitors:
- Schizophrenia: Start at 1.5 mg every 3 days
- Bipolar disorders: 1.5 mg every 3 days 1
Moderate CYP3A4 Inhibitors:
- Schizophrenia: Start at 1.5 mg every other day
- Bipolar disorders: 1.5 mg every other day 1
Efficacy
Schizophrenia
- Pooled responder rates: 31% for cariprazine 1.5-6 mg/day vs. 21% for placebo (NNT = 10)
- In relapse prevention: 24.8% vs. 47.5% relapse rates (NNT = 5) 2
Bipolar Depression
- Response rates (≥50% reduction in MADRS): 46.3% vs. 35.9% for placebo (NNT = 10)
- Remission rates (MADRS ≤10): 30.2% vs. 20.9% for placebo (NNT = 11) 4
Common Adverse Effects
The most common adverse events (≥5% and at least twice placebo rate):
Schizophrenia
- Extrapyramidal symptoms (NNH 15 for 1.5-3 mg/day)
- Akathisia (NNH 20 for 1.5-3 mg/day) 2
Bipolar Mania
- Extrapyramidal symptoms
- Akathisia
- Dyspepsia
- Vomiting
- Somnolence
- Restlessness 1
Bipolar Depression
- Nausea
- Akathisia
- Restlessness
- Extrapyramidal symptoms 1
Metabolic Profile
Vraylar has a favorable metabolic profile compared to many other antipsychotics:
- Minimal weight gain (NNH 34 for ≥7% weight gain)
- No clinically meaningful alterations in metabolic variables
- No significant impact on prolactin levels
- No QT interval prolongation 2
Clinical Pearls
- Titration is important: Start with 1.5 mg and titrate gradually to minimize side effects
- Long half-life: Effects of dose changes may take weeks to fully manifest
- Monitoring period: Due to the long half-life, monitor patients for several weeks after starting or changing doses
- Higher doses = more side effects: Doses above 6 mg daily do not provide additional benefit but increase adverse effects 1
- Bipolar depression dosing: Maximum dose is 3 mg daily, lower than for mania or schizophrenia
Warning
Vraylar carries a boxed warning for:
- Increased mortality in elderly patients with dementia-related psychosis
- Suicidal thoughts and behaviors when used as an antidepressant 1