cariprazine

General Information

Cariprazine (brand Vraylar) is an second-generation antipsychotic (SGA) that preferentially targets dopamine D3 receptors, supporting efficacy across schizophrenia and bipolar disorder mood states.

This profile emphasizes its role in schizophrenia, bipolar I mania/mixed episodes, bipolar depression, and adjunctive major depressive disorder (MDD; clinical depression) as add-on therapy to antidepressants.

The cariprazine compare view, cariprazine evidence feed, and cariprazine print page can support counseling and shared decision-making around efficacy, akathisia risk, and titration timelines; the schizophrenia hub and bipolar disorder hub link to broader care pathways.

Often chosen for negative-symptom improvement and bipolar depression coverage. Long-lived metabolites mean titration is slow and monitoring for akathisia and GI upset is important; metabolic impact is moderate.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Cariprazine stabilizes dopamine and serotonin activity via partial agonism at D3/D2 and 5-HT1A receptors coupled with 5-HT2 antagonism, balancing mesolimbic and mesocortical pathways.

Preferential D3 occupancy may contribute to negative-symptom gains and cognitive benefits highlighted in clinical trials.

• Partial agonist at dopamine D3>D2 receptors.
• Partial agonist at serotonin 5-HT1A; antagonist at 5-HT2A/5-HT2B receptors.
• Antagonist at adrenergic α1B and histamine H1 receptors.
• Minimal muscarinic receptor binding.

Metabolism and Pharmacokinetics

• Oral bioavailability ~50%; Tmax 3–6 hours; food has negligible effect on exposure.
• Greater than 90% plasma protein bound with extensive tissue distribution.
• Metabolized by CYP3A4 (major) and CYP2D6 (minor) to active metabolites desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR).
• Terminal half-life 2–4 days for parent, 1–2 days for DCAR, and up to 1–3 weeks for DDCAR; effective half-life ~7 days at steady state.
• Eliminated primarily in feces (~70%) with <10% renal excretion.

Dosing and Administration

• Schizophrenia: start 1.5 mg once daily; increase to 3 mg on day 2; adjust by 1.5–3 mg increments at ≥2-week intervals to 1.5–6 mg/day (max 6 mg).
• Bipolar I mania/mixed: initiate 1.5 mg once daily, increase to 3 mg on day 2, then titrate by 1.5 mg increments up to 6 mg/day.
• Bipolar I depression: 1.5 mg once daily for at least 14 days; may increase to 3 mg/day based on response.
• Adjunctive major depressive disorder (clinical depression): start 1.5 mg once daily with an antidepressant; may increase to 3 mg/day (max 3 mg/day).
• Label recommends halving the dose with strong CYP3A4 inhibitors; coadministration with strong CYP3A4 inducers is generally avoided; not recommended in severe hepatic impairment.

Adverse Effects

Interactions

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) increase exposure; label recommends reducing cariprazine dose by half and monitoring for akathisia or sedation.
• Strong CYP3A4 inducers (rifampin, carbamazepine, St. John’s wort) substantially lower exposure; coadministration is generally avoided.
• Moderate CYP3A4 inhibitors often warrant slower titration and closer monitoring.
• Additive CNS depression with alcohol, benzodiazepines, or opioids.
• May blunt efficacy of dopamine agonists (e.g., levodopa); this combination is often avoided when dopaminergic therapy is needed.

Other Useful Information

• Long-lived metabolites mean clinical response to dose changes can be delayed; allowing several weeks before adjusting again is common.
• Patients and caregivers can be advised on early akathisia; clinicians often manage it with dose adjustments, beta-blockers, or benzodiazepines.
• Low impact on QTc, but a baseline ECG is often considered in patients with cardiac risk or polypharmacy.
• Once-daily dosing at a consistent time (with or without food) helps maintain steady exposure.
• Metabolic monitoring typically includes baseline, 12 weeks, then annually.
• Comparing dopamine partial agonists side-by-side using the cariprazine compare view can help select alternatives when akathisia, cost, or residual symptoms prompt a switch.

References

1. VRAYLAR (cariprazine) prescribing information — DailyMed (2025)
2. FDA Vraylar Medr 2015
3. Cariprazine IN Acute Exacerbation OF Schizophrenia: A Randomized, Double Blind, Placebo Controlled Trial — Schizophrenia Research (2015)
4. Nemeth2017 Cariprazine Negative
5. AN 8 Week Randomized, Double Blind, Placebo Controlled Evaluation OF Cariprazine IN Bipolar I Depression — American Journal of Psychiatry (2016)
6. Efficacy OF Adjunctive LOW Dose Cariprazine IN Major Depressive Disorder — International Clinical Psychopharmacology (2018)