Cariprazine

(Vraylar®)

Vraylar®

Drug updated on 10/31/2024

Dosage FormCapsules (oral; 1.5 mg, 3 mg, 4.5 mg, 6 mg)
Drug ClassAtypical antipsychotics
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated for treatment of schizophrenia in adults
  • Indicated for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults
  • Indicated for treatment of depressive episodes associated with bipolar I disorder (bipolar depression) in adults
  • Indicated for adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults.

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Summary
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  • This summary is based on the review of 19 systematic review(s)/meta-analysis(es). [1-19]
  • Schizophrenia and Bipolar Disorder: Cariprazine effectively reduced global clinical severity and psychotic symptoms in schizophrenia and bipolar disorder patients, with higher doses yielding stronger improvements. Reductions included effect sizes for global clinical severity ranging from -0.25 (≤1.5 mg/day) to -0.45 (≥3 mg/day) and a mean difference (MD) in psychotic symptom scores of -6.74. Cariprazine also reduced depression (MD = -1.78), mania (MD = -5.72), and anxiety symptoms (MD = -1.24).
  • Major Depressive Disorder (MDD) and Bipolar I Disorder (BDI): Cariprazine was associated with reductions in depression severity on the MADRS (Montgomery-Asberg Depression Rating Scale) scale (MD = -1.49) and showed increased response (RR (relative risk) = 1.21) and remission rates (RR = 1.19) compared to placebo. In BDI, the reduction in MADRS scores was more pronounced (MD = -2.53) than in MDD (MD = -1.15), with BDI patients experiencing higher response (RR = 1.27) and remission rates (RR = 1.41).
  • Treatment-Resistant Depression (TRD): Cariprazine demonstrated limited effectiveness for TRD, with its maximum effective dose being 1.5 mg; lower doses of 0.5 to 1 mg were less effective, and both aripiprazole and brexpiprazole showed superior efficacy in TRD.
  • Acute Mania in Bipolar Disorder: Cariprazine reduced manic symptoms, as measured by the YMRS score (SMD = -0.52), with significant response (OR = 2.31) and remission rates (OR = 2.05), indicating its effectiveness in managing acute manic and mixed episodes in bipolar disorder.
  • Discontinuation and Common Adverse Effects: Cariprazine was associated with higher treatment discontinuation rates due to adverse events compared to placebo in MDD and bipolar disorder studies, with common adverse effects including somnolence, weight gain, and metabolic disturbances.
  • Extrapyramidal Side Effects (EPS): Cariprazine presented dose-dependent risks for EPS, with lower risk levels than haloperidol at high doses (maximum OR for haloperidol EPS = 7.56) but notable EPS risks relative to other antipsychotics, such as quetiapine and sertindole, which demonstrated lower EPS occurrence.
  • Specific Adverse Events in Bipolar Disorder: Cariprazine had a lower rate of somnolence compared to quetiapine and caused moderate weight gain, less than olanzapine but higher than lurasidone and aripiprazole.
  • The reviewed studies on cariprazine primarily involved adult populations with a median age of 31, covering both male and female participants with conditions including schizophrenia, bipolar I disorder, and major depressive disorder. In subgroup findings, cariprazine showed greater efficacy in bipolar I disorder compared to MDD, and real-world settings highlighted the impact of non-adherence in managing schizophrenia. Limited data were available for youth and geriatric populations, with recommendations for further study in these groups.

Product Monograph / Prescribing Information

Document TitleYearSource
Vraylar (cariprazine) Prescribing Information.2024AbbVie Inc., North Chicago, IL

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Efficacy of Cariprazine in the Psychosis Spectrum: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials in Schizophrenia and Bipolar Disorder2024CNS Drugs
Real-World Effectiveness, Economic, and Humanistic Outcomes of Selected Oral Antipsychotics in Patients with Schizophrenia: A Systematic Review Evaluating Global Evidence2024ClinicoEconomics and Outcomes Research
Cariprazine in the acute treatment of unipolar and bipolar depression: A systematic review and meta-analysis2024Journal of Affective Disorders
Comparative Efficacy of Dopamine Partial Agonists by Doses for Treatment-Resistant Depression: A Systematic Review and Dose-Response Model-Based Network Meta-analysis2024Journal of Clinical Psychopharmacology
Adjunctive cariprazine for major depressive disorder: a systematic review and meta-analysis2024CNS Spectrums
Efficacy and tolerability of FDA-approved atypical antipsychotics for the treatment of bipolar depression: a systematic review and network meta-analysis2024European Psychiatry
Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis2023Molecular Psychiatry
Comparison of antipsychotic dose equivalents for acute bipolar mania and schizophrenia2023BMJ Mental Health
Efficacy and safety/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder: a systematic review and meta-analysis2023Psychological Medicine
Real-Life Clinical Experience With Cariprazine: A Systematic Review of Case Studies2022Frontiers in Psychiatry
Comparative efficacy and tolerability of 32 oral and long-acting injectable antipsychotics for the maintenance treatment of adults with schizophrenia: a systematic review and network meta-analysis2022Lancet (London, England)
Augmentation strategies for treatment resistant major depression: A systematic review and network meta-analysis2022Journal of Affective Disorders
Efficacy and Tolerability of Combination Treatments for Major Depression: Antidepressants plus Second-Generation Antipsychotics vs. Esketamine vs. Lithium2021Journal of Psychopharmacology
Efficacy and tolerability of atypical antipsychotics for acute bipolar depression: a network meta-analysis2021BMC Psychiatry
New Developments in the Use of Atypical Antipsychotics in the Treatment of Bipolar Disorder: a Systematic Review of Recent Randomized Controlled Trials2021Current Psychiatry Reports
Real-World Data on the Adverse Metabolic Effects of Second-Generation Antipsychotics and Their Potential Determinants in Adult Patients: A Systematic Review of Population-Based Studies2021Advances in Therapy
Acceptability of Acute and Maintenance Pharmacotherapy of Bipolar Disorder: A Systematic Review of Randomized, Double-Blind, Placebo-Controlled Clinical Trials2020Journal of Clinical Psychopharmacology
Cariprazine in the treatment of Bipolar Disorder: A systematic review and meta-analysis2020Bipolar Disorders
Pharmacological interventions for treatment-resistant depression in adults2019The Cochrane Database of Systematic Reviews

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