Aripiprazole in bipolar depression: a pooled, post-hoc analysis by severity of core depressive symptoms

Abstract

Objective. This post-hoc analysis of pooled data from two similarly designed trials assessed the impact of aripiprazole monotherapy vs. placebo on treatment outcomes based on baseline severity of core depressive symptoms in patients with bipolar I disorder. Methods. Patients were classified as severely depressed (Bech-6 Total score > 15) or less severely depressed (Bech-6 Total score < 15). Efficacy was assessed by mean changes in Montgomery–Åsberg Depression Rating Scale (MADRS) Total and MADRS-6 subscale scores from baseline to endpoint using a mixed model repeated measures analysis. Results. A total of 133 patients (n = 62 on active aripiprazole) were classified as severely depressed and 612 patients (n = 309 aripiprazole) as less severely depressed. At endpoint, the mean MADRS Total score reduction for severely depressed patients receiving aripiprazole compared with placebo was –19.4 vs. –15.4 (P = 0.14), whereas MADRS-6 subscale score reduction for patients receiving aripiprazole compared with placebo was –13.8 vs. –10.3 (P = 0.07). Adverse event profiles were similar between the two severity groups. Conclusions. Symptomatic improvements assessed here suggest that aripiprazole monotherapy at the doses studied may provide some improvements in core symptoms of depression in patients with bipolar I disorder who were more severely depressed.

Key Words::

• Aripiprazole
• bipolar disorder
• bipolar depression
• efficacy
• tolerability

Acknowledgements

This study was supported by Bristol-Myers Squibb (Princeton, NJ, USA) and Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). Editorial support for the preparation of this manuscript was provided by Ogilvy Healthworld; funding was provided by Bristol-Myers Squibb. The authors would like to acknowledge the contributions of Andrei Pikalov, MD, PhD – a former employee of Otsuka America Pharmaceutical Inc.

Statement of Interests

Michael Thase has been an advisory/consultant for AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly & Co., Dey Pharma, L.P., Forest Laboratories, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Inc., Merck and Co. Inc., Neuronetics, Inc., Novartis, Otsuka, Ortho-McNeil Pharmaceuticals, Pamlab, L.L.C., Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Schering-Plough, Shire US Inc., Supernus Pharmaceuticals, Takeda and Transcept Pharmaceuticals. He has received grant support from the Agency for Healthcare Research and Quality, Eli Lilly and Company, GlaxoSmithKline, National Institute of Mental Health and Sepracor, Inc. He is on the speaker's bureau of AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly & Co., Merck and Co. Inc., Pfizer (formerly Wyeth Ayerst Pharmaceuticals). He has equity holdings in MedAvante, Inc. and receives royalties from the American Psychiatric Publishing, Inc., Guilford Publications, Herald House W.W. Norton & Company, Inc. His spouse is an employee of Embryon (Formerly Advogent; Embryon does business with Bristol-Myers Squibb and Pfizer/Wyeth).

Charles Bowden has received research grants from Janssen, Repligen, Pamlab, National Institutes of Mental Health, and National Institutes of Health Agency for Healthcare Research and Quality. He has also served as a consultant for Sanofi Aventis, BMS, Merck and Pfizer.

Michael Nashat is a registered Community Pharmacist. He is vice President of Pharmacy Affairs for the Prince Theodore Group of Pharmacies, is CEO of Health Synapse Inc., is a consultant with the Ministry of Health and Long Term Care of Ontario and is on the board of directors for the Canadian association of chain drug stores.

James M Eudicone, Berit X Carlson and Ronald Marcus are employees of Bristol-Myers Squibb.

Robert D McQuade is an employee of Otsuka Pharmaceutical Development & Commercialization.