Extended-release carbamazepine capsules as monotherapy in bipolar disorder

Pooled results from two randomised, double-blind, placebo-controlled trials

Richard H. Weisler, Robert Hirschfeld, Andrew J. Cutler, Thomas Gazda, Terence A. Ketter, Paul E. Keck, Alan Swann, Amir Kalali

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)219-321
Number of pages103
JournalCNS Drugs
Volume20
Issue number3
DOIs
StatePublished - 2006

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Carbamazepine
Bipolar Disorder
Capsules
Placebos
Depression
Meta-Analysis

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Neuropsychology and Physiological Psychology
  • Pharmacology

Cite this

Extended-release carbamazepine capsules as monotherapy in bipolar disorder : Pooled results from two randomised, double-blind, placebo-controlled trials. / Weisler, Richard H.; Hirschfeld, Robert; Cutler, Andrew J.; Gazda, Thomas; Ketter, Terence A.; Keck, Paul E.; Swann, Alan; Kalali, Amir.

In: CNS Drugs, Vol. 20, No. 3, 2006, p. 219-321.

Research output: Contribution to journalArticle

Weisler, Richard H. ; Hirschfeld, Robert ; Cutler, Andrew J. ; Gazda, Thomas ; Ketter, Terence A. ; Keck, Paul E. ; Swann, Alan ; Kalali, Amir. / Extended-release carbamazepine capsules as monotherapy in bipolar disorder : Pooled results from two randomised, double-blind, placebo-controlled trials. In: CNS Drugs. 2006 ; Vol. 20, No. 3. pp. 219-321.
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AU - Gazda, Thomas

AU - Ketter, Terence A.

AU - Keck, Paul E.

AU - Swann, Alan

AU - Kalali, Amir

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N2 - 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.

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