Efficacy and Safety of Once- versus Twice-Daily Carbamazepine Extended-Release Capsules for the Treatment of Manic Symptoms in Patients with Bipolar I Disorder.

Objective: To compare the efficacy and safety of carbamazepine extended-release capsules (CBZ-ERC) administered twice daily (BID) versus once daily for the treatment of manic symptoms associated with bipolar I disorder in adults.

Design: This was a Phase IIIb, randomized, double-blind, parallel-group, multicenter, 12-week study. Subjects were randomized (1:1) to CBZ-ERC once daily at bedtime (QHS) or BID. Dosing was initiated at CBZ-ERC 200mg/d and titrated to achieve an optimal dose (target dose, 800mg/d; maximum dose, 1600mg/d). The primary efficacy outcome variable was the Young Mania Rating Scale (YMRS). The Hamilton Rating Scale for Depression, 21-item version (HAM-D(21)), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions Scale-Bipolar Version (CGI-BP), and time to remission were secondary outcome variables. Safety measures included recording of adverse events, physical examination, vital signs (blood pressure, pulse rate, and weight), and clinical laboratory and electrocardiogram (ECG) parameters.

Results: BID and QHS dosing were equally effective in improving symptoms of bipolar disorder, as measured with the YMRS, HAM-D(21), MADRS, and CGI-BP. Both BID and QHS dosing significantly improved total scores on the YMRS, HAM-D(21), and MADRS at all time points without statistically significant differences between groups. All three components of the CGI-BP improved during the study, and a large percentage of subjects in both groups achieved remission without significant differences between groups. Both CBZ-ERC regimens appeared to be safe and well tolerated.

Conclusion: These results suggest QHS dosing may be a safe and effective alternative to BID dosing of CBZ-ERC for treating manic episodes for many adults with bipolar I disorder, although additional studies are needed to confirm this finding.