Extended-release carbamazepine capsules as monotherapy in bipolar disorder : pooled results from two randomised, double-blind, placebo-controlled trials.
OBJECTIVE
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.
Weisler
Richard H
RH
Department of Psychiatry and Behavioral Science, Duke University, Raleigh, North Carolina 27609, USA. rweisler@aol.com
Hirschfeld
Robert
R
Cutler
Andrew J
AJ
Gazda
Thomas
T
Ketter
Terence A
TA
Keck
Paul E
PE
Swann
Alan
A
Kalali
Amir
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D002214:Capsules / Q000627:therapeutic use; D002220:Carbamazepine / Q000627:therapeutic use*; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
D000927:Anticonvulsants; D002214:Capsules; D003692:Delayed-Action Preparations; D002220:Carbamazepine