A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes

Richard H. Weisler, Amir H. Kalali, Terence A. Ketter, Mohammed Bari, Stanley Cheren, Andrew Cutler, Louis Fabre, Joseph Goldberg, Alan Jacobson, Gregory Bishop, Saaid Khojasteh, Mary Ann Knesevich, Mark Lerman, Joseph Patrick McEvoy, William Privitera, Rakesh Ranjan, Robert Riesenberg, Craig Risch, David Sack, Rainder ShiwachAlan Swann, Richard Weisler, Adam Lowy, Michael Plopper, John Gilliam, David Walling, Alia Karim, Jeffrey Borenstein

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176 Scopus citations

Abstract

Background: Carbamazepine has been used to treat mania for over 2 decades. Most evaluations of carbamazepine have had important limitations, such as absence of a parallel placebo group, small sample size, or the confounding influence of concomitant treatment. All studies have used conventional, immediate-release carbamazepine formulations. We assessed the efficacy and safety of monotherapy with beaded, extended-release carbamazepine capsules (ERC-CBZ; SPD417) in bipolar disorder patients with manic or mixed episodes. Method: Following a single-blind placebo lead-in, DSM-IV-defined bipolar disorder patients with manic or mixed episodes were randomly assigned to receive ERC-CBZ (N = 101) or placebo (N = 103) for 3 weeks. Patients were hospitalized through the first 7 days of the double-blind period. ERC-CBZ was initiated at 400 mg/day and increased, as necessary and tolerated, up to 1600 mg/day. Efficacy was assessed weekly with the Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and Hamilton Rating Scale for Depression (HAM-D). Data were gathered from December 1999 to June 2001. Results: Ninety-six (47.1%) of 204 patients completed the study. The mean ± SD final ERC-CBZ dose was 756.44 ± 413.38 mg/day with a mean plasma drug level of 8.9 μg/mL. Starting at week 2, ERC-CBZ was associated with significantly greater improvements in YMRS (p = .032) using last-observation-carried-forward analyses. At end point, the responder rate (patients with at least a 50% decrease in YMRS score) also favored ERC-CBZ (41.5% vs. 22.4%; p = .0074). In a post hoc analysis of mixed patients, HAM-D score was significantly improved in patients remaining on ERC-CBZ treatment on day 21 (p = .01). Adverse events occurring more frequently in the ERC-CBZ group than in the placebo group included dizziness, nausea, and somnolence. Conclusion: We found ERC-CBZ to be effective in the first large, randomized, double-blind, placebo-controlled parallel trial of carbamazepine monotherapy in acute mania. This trial provides important additional evidence supporting the use of carbamazepine in acute mania.

Original languageEnglish (US)
Pages (from-to)478-484
Number of pages7
JournalJournal of Clinical Psychiatry
Volume65
Issue number4
DOIs
StatePublished - Apr 1 2004

ASJC Scopus subject areas

  • Psychiatry and Mental health

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    Weisler, R. H., Kalali, A. H., Ketter, T. A., Bari, M., Cheren, S., Cutler, A., Fabre, L., Goldberg, J., Jacobson, A., Bishop, G., Khojasteh, S., Knesevich, M. A., Lerman, M., McEvoy, J. P., Privitera, W., Ranjan, R., Riesenberg, R., Risch, C., Sack, D., ... Borenstein, J. (2004). A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. Journal of Clinical Psychiatry, 65(4), 478-484. https://doi.org/10.4088/JCP.v65n0405