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
Y1 - 2004/4
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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U2 - 10.4088/JCP.v65n0405
DO - 10.4088/JCP.v65n0405
M3 - Article
C2 - 15119909
AN - SCOPUS:2442534824
SN - 0160-6689
VL - 65
SP - 478
EP - 484
JO - Diseases of the Nervous System
JF - Diseases of the Nervous System
IS - 4
ER -
