A 6-month, multicenter, open-label evaluation of beaded, extended-release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes.

BACKGROUND

Carbamazepine is frequently used for treating bipolar disorder, but few large trials have assessed its efficacy in preventing relapse. We evaluated open-label monotherapy with beaded extended-release carbamazepine capsules (ERC-CBZ; SPD417) as continuation and short-term maintenance therapy in bipolar disorder patients with manic and mixed episodes.

METHOD: A 6-month, open-label study enrolled 92 patients with DSM-IV bipolar disorder (most recent episode: 67% [N = 62] mixed, 33% [N = 30] manic) who had participated in 2 previous 3-week, double-blind, placebo-controlled studies. Subjects received beaded ERC-CBZ (200-1600 mg/day), titrated at investigators' discretion to a final mean dose of 938 mg/day and serum carbamazepine concentration of 6.6 microg/mL. The primary efficacy measure was time to relapse, and secondary efficacy measures included Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and Hamilton Rating Scale for Depression (HAM-D) scores. Data were gathered from January 2000 to January 2002.

RESULTS

Of 77 patients analyzed in the intent-to-treat population, 11 (14.3%) relapsed. Fifty-three patients (68.8%) discontinued early, including 18 (23.4%) due to adverse events. Observed mean time to relapse was 61.1 days, while estimated mean time to relapse based on the Kaplan-Meier model was 141.8 days. Improvements on the YMRS, CGI, and HAM-D from the beginning of prior double-blind treatment were maintained. The most common adverse events were headache, dizziness, and rash. No significant weight gain was noted.

CONCLUSION

We noted a low relapse rate with beaded ERC-CBZ in this 6-month trial. Adverse events were generally mild to moderate and were typical of those associated with carbamazepine. Controlled studies are warranted to further explore the efficacy of beaded ERC-CBZ in preventing relapse in bipolar disorder.