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 Shiwach & 8 others Alan Swann, Richard Weisler, Adam Lowy, Michael Plopper, John Gilliam, David Walling, Alia Karim, Jeffrey Borenstein

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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

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Carbamazepine
Bipolar Disorder
Capsules
Placebos
Dizziness
Diagnostic and Statistical Manual of Mental Disorders
Sample Size
Nausea
Observation
Depression
Safety
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Psychiatry and Mental health

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A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. / Weisler, Richard H.; Kalali, Amir H.; Ketter, Terence A.; Bari, Mohammed; Cheren, Stanley; Cutler, Andrew; Fabre, Louis; Goldberg, Joseph; Jacobson, Alan; Bishop, Gregory; Khojasteh, Saaid; Knesevich, Mary Ann; Lerman, Mark; McEvoy, Joseph Patrick; Privitera, William; Ranjan, Rakesh; Riesenberg, Robert; Risch, Craig; Sack, David; Shiwach, Rainder; Swann, Alan; Weisler, Richard; Lowy, Adam; Plopper, Michael; Gilliam, John; Walling, David; Karim, Alia; Borenstein, Jeffrey.

In: Journal of Clinical Psychiatry, Vol. 65, No. 4, 01.04.2004, p. 478-484.

Research output: Contribution to journalArticle

Weisler, RH, Kalali, AH, Ketter, TA, Bari, M, Cheren, S, Cutler, A, Fabre, L, Goldberg, J, Jacobson, A, Bishop, G, Khojasteh, S, Knesevich, MA, Lerman, M, McEvoy, JP, Privitera, W, Ranjan, R, Riesenberg, R, Risch, C, Sack, D, Shiwach, R, Swann, A, Weisler, R, Lowy, A, Plopper, M, Gilliam, J, Walling, D, Karim, A & 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, vol. 65, no. 4, pp. 478-484. https://doi.org/10.4088/JCP.v65n0405
Weisler, Richard H. ; Kalali, Amir H. ; Ketter, Terence A. ; Bari, Mohammed ; Cheren, Stanley ; Cutler, Andrew ; Fabre, Louis ; Goldberg, Joseph ; Jacobson, Alan ; Bishop, Gregory ; Khojasteh, Saaid ; Knesevich, Mary Ann ; Lerman, Mark ; McEvoy, Joseph Patrick ; Privitera, William ; Ranjan, Rakesh ; Riesenberg, Robert ; Risch, Craig ; Sack, David ; Shiwach, Rainder ; Swann, Alan ; Weisler, Richard ; Lowy, Adam ; Plopper, Michael ; Gilliam, John ; Walling, David ; Karim, Alia ; Borenstein, Jeffrey. / A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. In: Journal of Clinical Psychiatry. 2004 ; Vol. 65, No. 4. pp. 478-484.
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TY - JOUR

T1 - A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes

AU - Weisler, Richard H.

AU - Kalali, Amir H.

AU - Ketter, Terence A.

AU - Bari, Mohammed

AU - Cheren, Stanley

AU - Cutler, Andrew

AU - Fabre, Louis

AU - Goldberg, Joseph

AU - Jacobson, Alan

AU - Bishop, Gregory

AU - Khojasteh, Saaid

AU - Knesevich, Mary Ann

AU - Lerman, Mark

AU - McEvoy, Joseph Patrick

AU - Privitera, William

AU - Ranjan, Rakesh

AU - Riesenberg, Robert

AU - Risch, Craig

AU - Sack, David

AU - Shiwach, Rainder

AU - Swann, Alan

AU - Weisler, Richard

AU - Lowy, Adam

AU - Plopper, Michael

AU - Gilliam, John

AU - Walling, David

AU - Karim, Alia

AU - Borenstein, Jeffrey

PY - 2004/4/1

Y1 - 2004/4/1

N2 - 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.

AB - 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.

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