Safety of carbamazepine extended-release capsules used in combination with other psychotropic medications for the treatment of bipolar I disorder.
OBJECTIVE
To evaluate the safety and efficacy of carbamazepine extended-release capsules (CBZ-ERC) in combination with other psychotropic medications for the treatment of bipolar I disorder.


METHODS
In this Phase IIIb, open-label, eight-week, observational, polypharmacy study, adult subjects were started on CBZ-ERC 200mg and titrated over four weeks to optimal dose (1600mg/d maximum). Concomitant lithium and atypical antipsychotics (olanzapine, risperidone, quetiapine, aripiprazole) were permitted. Safety assessments included adverse events, laboratory parameters, physical examination, medication history, vital signs, and electrocardiogram. Efficacy measures included the Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impressions Scale-Bipolar Version (CGI-BP). All data were summarized using descriptive statistics.


RESULTS
Overall, 45 (84.9%) subjects reported treatment-emergent adverse events (TEAEs); most were mild or moderate in severity. The most commonly reported TEAEs were somnolence (n=14, 26.4%), sedation (n=12, 22.6%), dizziness (n=11, 20.8%), headache (n=9, 17.0%), and nausea (n=7, 13.2%). There were no clinically significant changes in vital signs, including weight. Mean changes in laboratory parameters were small, with values that were within the normal range for the majority of subjects. Few changes relative to screening for other safety parameters occurred. Mean total YMRS score decreased from baseline at each study visit. HAM-D and MADRS scores decreased from baseline at Weeks 4 and 8, and all three CGI-BP components (overall bipolar disorder, mania, and depression) improved during the study.


CONCLUSIONS
CBZ-ERC appears to be safe and effective for use in combination with atypical antipsychotics and lithium for treatment of bipolar I disorder.
Weisler
Richard H
RH
Dr. Weisler is from Duke University Medical Center, Durham, North Carolina, and University of North Carolina at Chapel Hill Departments of Psychiatry, Raleigh, North Carolina.
Kalali
Amir H
AH
Cutler
Andrew J
AJ
Gazda
Thomas D
TD
Ginsberg
Lawrence
L