What is the recommended dosage and usage of Vraylar (cariprazine) for treating schizophrenia and bipolar disorder?

Vraylar (Cariprazine) Dosing and Administration

Schizophrenia

For schizophrenia, start cariprazine at 1.5 mg once daily, increase to 3 mg on Day 2, and titrate to a target range of 1.5-6 mg daily based on response and tolerability. 1

• The maximum recommended dose is 6 mg daily, as doses above this do not provide additional benefit but increase dose-related adverse reactions 1
• Dose adjustments can be made in 1.5 mg or 3 mg increments after Day 2 1
• Cariprazine can be taken with or without food 1

Bipolar I Disorder - Manic or Mixed Episodes

For acute bipolar mania, start at 1.5 mg once daily, increase to 3 mg on Day 2, and titrate within the recommended range of 3-6 mg daily. 1

• The maximum recommended dose is 6 mg daily 1
• Further adjustments can be made in 1.5 mg or 3 mg increments based on clinical response 1
• Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions 1

Bipolar I Disorder - Depressive Episodes

For bipolar depression, start at 1.5 mg once daily and increase to 3 mg daily on Day 15 if needed, with a maximum dose of 3 mg daily. 1

• The recommended dosage range is 1.5-3 mg daily 1
• Cariprazine demonstrated efficacy for bipolar depression with NNT of 10 for response and 11 for remission 2
• The 1.5 mg dose may have better tolerability than 3 mg while maintaining efficacy 2

Major Depressive Disorder (Adjunctive Therapy)

As adjunctive therapy to antidepressants for MDD, start at 1.5 mg once daily and increase to 3 mg on Day 15 if needed, with a maximum dose of 3 mg daily. 1

• Dose titration at intervals less than 14 days resulted in higher incidence of adverse reactions 1
• The maximum recommended dose is 3 mg daily 1

Critical Pharmacokinetic Considerations

Due to cariprazine's extremely long half-life (2-5 days for parent compound, 2-3 weeks for active metabolite didesmethyl-cariprazine), full therapeutic effects and side effects may take several weeks to manifest. 3, 4

• Monitor patients for adverse reactions and treatment response for several weeks after starting and after each dosage change 1
• The active metabolite achieves several times higher systemic exposure than the parent compound 3, 4
• Changes in dose will not be fully reflected in plasma for several weeks 1

Drug Interactions and Dose Adjustments

Strong CYP3A4 Inhibitors

When initiating cariprazine with a strong CYP3A4 inhibitor, start at 1.5 mg every 3 days for schizophrenia, bipolar depression, or MDD adjunctive therapy. 1

• For schizophrenia, can increase to 1.5 mg every other day if needed 1
• For patients already on cariprazine 1.5-3 mg daily, reduce to 1.5 mg every 3 days when adding a strong inhibitor 1
• For patients on 4.5-6 mg daily, reduce to 1.5 mg every other day 1

Moderate CYP3A4 Inhibitors

When initiating cariprazine with a moderate CYP3A4 inhibitor, start at 1.5 mg every other day. 1

• For schizophrenia, can increase to 1.5 mg daily if needed 1
• For patients already on cariprazine 1.5-3 mg daily, reduce to 1.5 mg every other day 1
• For patients on 4.5-6 mg daily, reduce to 1.5 mg daily 1

CYP3A4 Inducers

Concomitant use with CYP3A4 inducers is not recommended. 1

Most Common Adverse Reactions

The most common adverse reactions include extrapyramidal symptoms, akathisia, nausea, restlessness, insomnia, and constipation, with specific profiles varying by indication. 1

• Schizophrenia: extrapyramidal symptoms and akathisia (≥5% and twice placebo rate) 1
• Bipolar mania: extrapyramidal symptoms, akathisia, dyspepsia, vomiting, somnolence, and restlessness 1
• Bipolar depression: nausea, akathisia, restlessness, and extrapyramidal symptoms 1
• MDD adjunctive: akathisia, restlessness, fatigue, constipation, nausea, insomnia, increased appetite, dizziness, and extrapyramidal symptoms 1
• Discontinuation due to adverse events: 6.7% vs 4.8% placebo (NNH 51, not significant) 2

Special Populations and Precautions

Female patients of childbearing age should use effective contraception when taking cariprazine. 3

Cariprazine is contraindicated in patients with known hypersensitivity to the medication. 1

Clinical Advantages

Cariprazine may be particularly advantageous for patients with predominant negative symptoms of schizophrenia, as it is recommended as a suitable option for this indication. 5, 6

• The 2025 Lancet Psychiatry guidelines recommend cariprazine or aripiprazole when switching antipsychotics for persistent negative symptoms 5
• Cariprazine's D3-preferring receptor profile contributes to efficacy across multiple symptom domains including negative symptoms, cognitive impairment, and anhedonia 6
• Minimal metabolic changes make it suitable for patients with metabolic concerns 6