Extended-Release Carbamazepine Capsules as Monotherapy in Bipolar Disorder
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Objectives: Recently, two large, 3-week, randomised, double-blind, placebo-controlled trials using nearly identical protocols demonstrated that monotherapy with carbamazepine extended-release capsules (CBZ-ERC) was effective for the treatment of acute mania in patients with bipolar I disorder. By pooling data from these two trials, a more highly powered analysis of the efficacy and safety of CBZ-ERC in bipolar I disorder could be conducted.
Methods: Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Clinical Global Impression (CGI)-Severity (CGI-S) scale, the CGI-Improvement (CGI-I) scale and the Hamilton Depression Rating Scale (HDRS). A sub-analysis of the data based on manic versus mixed presentation was performed, as well as sub-analyses by age, sex and ethnicity.
Results: Of the 443 randomised patients in the pooled population, 240 completed the studies. Forty-two percent of CBZ-ERC-treated patients did not complete the studies, compared with 50% of placebo-treated patients (p = 0.087). Ten percent of patients given CBZ-ERC withdrew because of lack of efficacy, compared with 22% of patients given placebo (p < 0.001). At endpoint, CBZ-ERC compared with placebo was associated with significant improvements in mean YMRS total scores in patients experiencing both manic (p < 0.0001) and mixed (p < 0.01) episodes, using last-observation-carried-forward analyses. CGI-I and CGI-S scores also showed significant improvements from baseline for both manic and mixed patients at endpoint. In patients with mixed episodes, at endpoint there was a mean improvement in HDRS total score of 4.8 points with CBZ-ERC, compared with 2.3 points with placebo (p < 0.05). Ninety percent of patients given CBZ-ERC experienced an adverse event, compared with 64% of those patients given placebo. Discontinuation because of adverse events occurred in 10.8% of patients taking CBZ-ERC, compared with 5.5% of patients taking placebo.
Conclusions: These results confirm previous findings that CBZ-ERC is effective in the treatment of bipolar I disorder patients with either acute manic or mixed episodes. These data suggest that further randomised controlled studies are warranted to delineate the effect of CBZ-ERC on depressive symptoms in patients with bipolar disorder.
KeywordsBipolar Disorder Carbamazepine Hamilton Depression Rate Scale Manic Episode Young Mania Rate Scale
This work was supported by a grant from Shire, Wayne, PA, USA. Editorial support for the preparation of this manuscript was provided by David Danese, MA, from Precept Educational Sciences, Berkeley Heights, NJ, USA.
SPD417 Study Group: Anne Anndorn, Galveston, TX, USA; Mohammed Bari, Chula Vista, CA, USA; Louise Beckett, Oklahoma City, OK, USA; Gregory Bishop, San Diego, CA, USA; Jeffrey Borenstein, Holliswood, CA, USA; David Brown, Austin, TX, USA; Stanley Cheren, Natick, MA, USA; Andrew Cutler, Winter Park, FL, USA; Louis Fabre Jr, Houston, TX, USA; Shiv Gautam, Jaipur, India; Thomas Gazda, Phoenix, AZ, USA; John H. Gilliam, Richmond, VA, USA; Joseph Goldberg, New York, NY, USA; Alan Jacobson, North Miami, FL, USA; Arifulla Khan, Bellevue, WA, USA; Saaid Khojasteh, St Charles, MO, USA; Mary Ann Knesevich, Dallas, TX, USA; Mark Lerman, Hoffman Estates, IL, USA; H. Edward Logue, Birmingham, AL, USA; Adam Lowy, Washington, DC, USA; David Marks, La Mesa, CA, USA; Joseph McEvoy, Butner, NC, USA; Denis Mee-Lee, Honolulu, HI, USA; Jitendra Nagpal, Nehru Nagar, New Delhi, India; Teresa Pigott, Gainesville, FL, USA; Michael Plopper, San Diego, CA, USA; William Privitera, Austin, TX, USA; Nadukuru Nooka Raju, Visakhapatnam, India; Rakesh Ranjan, Medina, OH, USA; Robert Riesenberg, Atlanta, GA, USA; Craig Risch, Charleston, SC, USA; David Sack, Cerritos, CA, USA; P.S.V.N. Sharma, Karnataka, India; Rajinder Shiwach, Terrell, TX, USA; Krishnamachari Srinivasan, Bangalore, India; Alan Swann, Houston, TX, USA; Tram Tran-Johnson, San Diego, CA, USA; Jitendra Kumar Trivedi, Lucknow, India; Richard Weisler, Raleigh, NC, USA; Craig Wronski, Pico Rivera, CA, USA.
Financial disclosure: Dr Weisler has received grant/research support from, is a consultant to, and/or is a speaker for Abbott Laboratories, AstraZeneca, Biovail, Bristol-Myers Squibb, Cephalon, Corcept, Eisai, Eli Lilly & Company, Forest Pharmaceuticals, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, Medicinova, Merck, Novartis, Organon, Pfizer, Saegis, Sanofi-Synthelabo, Schwabe, Shire, Solvay, Synaptic, TAP Pharmaceuticals, UCB Pharma, Vela and Wyeth Pharmaceuticals. Dr Weisler is a stockholder in Bristol-Myers Squibb, Merck and Pfizer. Dr Hirschfeld is a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Eli Lilly & Company, Novartis, Organon, Inc., Pfizer, Shire, UCB Pharma and Wyeth Pharmaceuticals. Dr Cutler has received grant/research support from, is a speaker for, and/or is a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Otsuka, Pfizer, Shire, GlaxoSmithKline, Solvay Pharmaceuticals, Eli Lilly & Company, Sanofi-Aventis, Wyeth Pharmaceuticals, Organon, Johnson & Johnson, Cephalon, Forest Pharmaceuticals, Jazz Pharmaceuticals, Medicinova and Merck. Dr Gazda is a speaker for AstraZeneca, Bristol-Myers Squibb, Janssen, Pfizer, Sanofi-Aventis and Shire. Dr Ketter has received grant/research support from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eisai Inc., Elan Pharmaceuticals, Eli Lilly & Company, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Shire, Solvay Pharmaceuticals and Wyeth Pharmaceuticals; is a consultant to Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Corcept Therapeutics, Elan Pharmaceuticals, Eli Lilly & Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Jazz Pharmaceuticals, Novartis, Pfizer, Shire, Solvay Pharmaceuticals, UCB Pharmaceuticals and Wyeth Pharmaceuticals; and has received lecture honoraria from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Pfizer and Shire. Dr Keck is a consultant to and/or a member of scientific advisory boards of Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutica, Eli Lilly & Company, Ortho-McNeil, Pfizer and Shire. Dr Swann has received grant/research support from Abbott Laboratories, Pfizer, Janssen, CIBA, Eli Lilly & Company, GlaxoSmithKline, Shire, Novartis, and UCB-Pharma; is a consultant to GlaxoSmithKline, Abbott Laboratories, Janssen, Shire, Novartis, Ortho McNeil and AstraZeneca; and is a speaker for Abbott Laboratories, Eli Lilly & Company, Pfizer, GlaxoSmithKline, Parke Davis and Ortho McNeil. Dr Kalali is a consultant to and speaker for Shire.
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