The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis

Abstract

Background: Schizophrenia is a chronic and debilitating neuropsychiatric disorder that often requires long-term pharmacotherapy to manage symptoms and prevent relapse. Cariprazine is a potent dopamine D3 and D2 receptor partial agonist that is FDA-approved in the US for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults; the recommended dose range is 1.5-6 mg/d.

Methods: To further characterize the long-term safety of cariprazine, data from two 48-week open-label, flexible-dose extension studies were pooled for post hoc analyses. Outcomes were evaluated in the pooled safety population (patients who received ≥1 dose of cariprazine during an open-label extension period); findings were summarized using descriptive statistics for the overall cariprazine group and in modal daily dose groups (1.5-3, 4.5-6, and 9 mg/d).

Results: Of the 679 patients in the overall cariprazine safety population, 40.1% completed the study. The only adverse events (AEs) leading to discontinuation of ≥2% of patients in any dose group were akathisia, worsening of schizophrenia, and psychotic disorder. Treatment-emergent AEs (TEAEs) of akathisia, insomnia, weight increased, and headache were reported in ≥10% of the overall population. Mean prolactin levels decreased in all dose groups (overall, -15.4 ng/mL). Clinically insignificant changes in aminotransferase levels and alkaline phosphatase were observed; no dose-response relationship was observed across groups. Mean total (-5.3 mg/dL), low-density lipoprotein (-3.5 mg/dL), and high-density lipoprotein (-0.8 mg/dL) cholesterol levels decreased; no dose-response relationship was observed for metabolic parameters. Mean change in body weight was 1.58 kg; body weight increase and decrease ≥7% occurred in 27% and 11% of patients, respectively. Mean changes in cardiovascular parameters, including blood pressure and pulse, were generally not considered clinically significant. EPS-related TEAEs that occurred in ≥5% of patients were akathisia, tremor, restlessness, and extrapyramidal disorder.

Conclusion: In these post hoc pooled analyses of data from 2 long-term open-label studies, treatment with cariprazine was generally safe and well tolerated. Results support the safety and tolerability of cariprazine within the FDA-recommended dose range of 1.5-6 mg/d for schizophrenia.

Clinical trials registration: NCT01104792, NCT00839852.

Keywords: Atypical antipsychotic; Cariprazine; Long-term safety; Open-label; Post hoc analysis; Schizophrenia.

Conflict of interest statement

Ethics approval and consent to participate

The constituent clinical studies were conducted in full compliance with Food and Drug Administration guidelines for good clinical practice and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. The protocol of each study was approved by an institutional review board at sites in the United States or independent ethics committee at sites outside of the United States (Additional file 1). The studies were conducted in compliance with guidelines for good clinical practice; all patients gave informed written consent to participate.

Consent for publication

Not applicable.

Competing interests

HN has been a consultant for Acadia, Alkermes, Allergan, Boehringer Ingelheim, Grünenthal USA, Inc., Janssen Pharmaceuticals, Inc., Lundbeck, Merck Sharp & Dohme Corp., Novartis Corporation, Otsuka Pharmaceutical Co., Ltd., Roche/Genentech, Sunovion Pharmaceuticals, Inc., and Vanda Pharmaceuticals; he has served on speakers’ bureaus for Acadia, Alkermes, Allergan, Janssen Pharmaceuticals, Inc., Otsuka Pharmaceuticals, Sunovion Pharmaceuticals, Inc. and Vanda; he has received grant/research support from Forest Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Ltd., and Roche/Genentech. AC has received research grants and consultant/speaker fees from Acadia, Alkermes, Allergan, AstraZeneca, Braeburn Pharmaceuticals, Forum Pharmaceuticals, Janssen (Johnson & Johnson), Eli Lilly, Lundbeck, Neurocrine, Novartis, Otsuka, Reckitt Benckiser, Sunovion, Takeda, Teva, and Vanda. SD, WE, YW, and KL acknowledge a potential conflict of interest as employees of Allergan. IL and GN acknowledge a potential conflict of interest as employees of Gedeon Richter Plc.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.