An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine in Patients With Bipolar I Depression
Publication: American Journal of Psychiatry
Abstract
Objective:
The authors evaluated the efficacy, safety, and tolerability of cariprazine, an atypical antipsychotic candidate, in adult patients with acute bipolar I depression.
Method:
This was an 8-week multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in adult patients with bipolar I disorder experiencing a current major depressive episode. Patients were randomly assigned (1:1:1:1) to receive placebo or cariprazine at 0.75, 1.5, or 3.0 mg/day. The primary and secondary efficacy parameters were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions severity subscale (CGI-S), respectively, analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population.
Results:
The intent-to-treat population comprised 571 patients (141 in the placebo group and 140, 145, and 145 in the cariprazine 0.75-, 1.5-, and 3.0-mg/day groups). Cariprazine at 1.5 mg/day showed significantly greater improvement on MADRS total score change from baseline to week 6 compared with placebo; the least squares mean difference was −4.0 (95% CI=−6.3, −1.6; significant after adjustment for multiple comparisons). Cariprazine at 3.0 mg/day showed greater MADRS score reduction than placebo (−2.5, 95% CI=−4.9, −0.1; not significant when adjusted for multiple comparisons). The 0.75 mg/day dosage was similar to placebo. A similar pattern for significance was observed on the CGI-S (1.5 mg/day: least squares mean difference=−0.4, 95% CI=−0.6, −0.1; 3.0 mg/day: −0.3, 95% CI=−0.5, −0.0). The most common adverse events (≥10%) in cariprazine-treated patients were akathisia and insomnia; weight gain was slightly higher with cariprazine than with placebo.
Conclusions:
Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated, suggesting efficacy for the treatment of bipolar I depression.
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Information & Authors
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Published In
History
Received: 4 February 2015
Revision received: 29 May 2015
Revision received: 29 July 2015
Accepted: 14 August 2015
Published online: 6 November 2015
Published in print: March 01, 2016
Authors
Funding Information
Dr. Durgam is an employee and stockholder in Allergan. Dr. Earley is an employee of Allergan and owns stock in Allergan, AstraZeneca, and Eli Lilly. Dr. Lipschitz is a former employee of Forest Research Institute. Dr. Guo is an employee of Allergan. Dr. Laszlovszky is an employee of Gedeon Richter. Dr. Németh is an employee of Gedeon Richter. Dr. Vieta has received grants from or served as consultant, adviser, or speaker for Alexza, Almirall, AstraZeneca, Bristol-Myers Squibb, Cephalon, Elan, Eli Lilly, Ferrer, Forest Research Institute, Gedeon Richter, GlaxoSmithKline, Janssen-Cilag, Jazz, Johnson & Johnson, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, Schering-Plough, the Seventh European Framework Programme, Shire, the Spanish Ministry of Science and Innovation, the Stanley Medical Research Institute, Sunovion, Takeda, Teva, United BioSource Corporation, and Wyeth. Dr. Calabrese has received funding from the Department of Defense, the Health Resources Services Administration, and NIMH; research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, the Cleveland Foundation, Eli Lilly, GlaxoSmithKline, Janssen, NARSAD, Repligen, the Stanley Medical Research Institute, Takeda, and Wyeth; served on advisory boards for Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo, EPI Q, Forest Laboratories, the France Foundation, Gedeon Richter, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, Merck, Neurosearch, Ortho-McNeil, Otsuka, Pfizer, Repligen, Schering-Plough, Servier, Solvay, Supernus, Synosia, Takeda, and Wyeth; and provided CME lectures supported by AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson & Johnson, Merck, Sanofi-Aventis, Schering-Plough, Pfizer, Solvay, and Wyeth. Dr. Yatham has received research support from or served as a consultant or speaker for AstraZeneca, Bristol-Myers Squibb, the Canadian Psychiatric Foundation, Canadian Institutes of Health Research, Dainippon Sumitomo, Forest, GlaxoSmithKline, Johnson & Johnson, Lilly, Lundbeck, NARSAD, Novartis, Pfizer, Servier, the Stanley Foundation, Sunovion, Valeant, and Wyeth.
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