Cariprazine Treatment of Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Phase 3 Study
Publication: American Journal of Psychiatry
Abstract
Objective:
Cariprazine, a dopamine D3/D2 and 5-HT1A receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression.
Methods:
In a double-blind placebo-controlled study, adult participants (18–65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity.
Results:
Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were −2.5 (95% CI=−4.6, −0.4) for cariprazine at 1.5 mg/day and −3.0 (95% CI=−5.1, −0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, −0.2 [95% CI=−0.5, 0.0] for the 1.5 mg/day group and −0.3 [95% CI=−0.5, 0.0] for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups.
Conclusions:
Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression.
Formats available
You can view the full content in the following formats:
Supplementary Material
File (appi.ajp.2018.18070824.ds001.pdf)
- Download
- 148.76 KB
Information & Authors
Information
Published In
History
Received: 13 July 2018
Revision received: 19 November 2018
Accepted: 31 December 2018
Published online: 8 March 2019
Published in print: June 01, 2019
Keywords
Authors
Funding Information
Dr. Earley is an employee of Allergan and a former employee of Forest Laboratories, and he owns stock in Allergan, AstraZeneca, and Eli Lilly. Drs. Burgess and Rekeda are employees of Allergan and own stock in the company. Ms. Dickinson is an employee of Allergan. Drs. Szatmári and Németh are employees of Gedeon Richter. Dr. McIntyre has served as a consultant for, has received speaking fees from, sits on the advisory board of, and/or receives research funding from Allergan, AstraZeneca, Eli Lilly, Forest, Janssen Ortho, Lundbeck, Merck, Minerva, Otsuka, Pfizer, Purdue, Shire, Sunovion, and Takeda. Dr. Sachs is a founder, employee, and shareholder of Concordant Rater Systems; he has served as a consultant for Allergan, Astellas, AstraZeneca, Blackthorn, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Intracellular Therapies, Otsuka, Pfizer, Repligen, Sepracor, Sunovion, Takeda, and Wyeth; and he has served on speakers or advisory boards for Astellas, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Sanofi, Sepracor, Takeda, and Wyeth. Dr. Yatham has received research support from or served as a consultant or speaker for Alkermes, AstraZeneca, Bristol-Myers Squibb, the Canadian Psychiatric Foundation, the Canadian Institutes of Health Research, Dainippon Sumitomo, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Lundbeck, NARSAD, Novartis, Otsuka, Pfizer, Servier, the Stanley Foundation, Sunovion, Valeant, and Wyeth.
Metrics & Citations
Metrics
Citations
Export Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
There are no citations for this item
View Options
Get Access
Login options
Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.
Personal login Institutional Login Open Athens loginNot a subscriber?
PsychiatryOnline subscription options offer access to the DSM-5-TR® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.
Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).