Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial.
BACKGROUND
Although carbamazepine has long been used for the treatment of acute mania, only recently was its efficacy confirmed in a large, multicenter, parallel-group, placebo-controlled, randomized trial. In the present study, we further evaluated the efficacy and safety of monotherapy with beaded, extended-release carbamazepine capsules (ERC-CBZ) in patients with bipolar I disorder experiencing manic or mixed episodes.


METHODS
Hospitalized bipolar I disorder (DSM-IV criteria) patients (N = 239) with manic or mixed episodes were randomly assigned on a double-blind basis to receive ERC-CBZ or placebo for 3 weeks, following a single-blind placebo lead-in. Treatment with ERC-CBZ was initiated at 200 mg twice daily, and investigators were encouraged to increase doses, as necessary and tolerated, by 200 mg/day 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. The study was conducted from July 23, 2002, to April 1, 2003.


RESULTS
144 patients (60.3%) completed the study, with a significant number of placebo patients discontinuing due to lack of efficacy (p < .001). Extended-release carbamazepine treatment was associated with significant improvements in mean YMRS total and CGI total scores, using last-observation-carried-forward analyses, beginning at day 7 (p < .05). Adverse events occurring more frequently in the ERC-CBZ-treated group included dizziness (39.3%), somnolence (30.3%), and nausea (23.8%) [corrected] Patients taking ERC-CBZ experienced a significant increase in total cholesterol, composed of increases in both high-density and low-density lipoproteins.


CONCLUSIONS
Extended-release carbamazepine monotherapy had significantly greater efficacy compared with placebo in the treatment of acute mania in this large, randomized, double-blind, placebo-controlled trial.
Weisler
Richard H
RH
Department of Psychiatry and Behavioral Sciences, Duke University, 700 Spring Forest, Suite 125, Raleigh, NC 27609, USA. rweisler@aol.com
Keck
Paul E
PE
Swann
Alan C
AC
Cutler
Andrew J
AJ
Ketter
Terence A
TA
Kalali
Amir H
AH
D000208:Acute Disease; D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001259:Ataxia / Q000139:chemically induced; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D015990:Placebo Effect; D011569:Psychiatric Status Rating Scales; D012893:Sleep Wake Disorders / Q000139:chemically induced; D016896:Treatment Outcome
D018692:Antimanic Agents; D003692:Delayed-Action Preparations; D002220:Carbamazepine