Combination therapy of zonisamide and bupropion for weight reduction in obese women: a preliminary, randomized, open-label study.

OBJECTIVE Zonisamide and bupropion have been investigated for weight reduction in obese adults. We conducted a preliminary study comparing the effect on body weight of the combination of these 2 drugs versus zonisamide monotherapy. METHOD This was a 12-week, randomized, open-label, parallel-group comparison of 2 active interventions conducted from October 2003 to June 2004. Eighteen obese women (mean [SE] body mass index of 36.8 [1.2] kg/m(2)) were randomly assigned to receive the combination of zonisamide and bupropion (N = 9) or zonisamide alone (N = 9). All subjects were prescribed a balanced hypocaloric diet (500 kcal/day deficit) and compliance was monitored with self-rated food diaries. Zonisamide therapy was started at 100 mg/day, with a gradual increase to 400 mg/day over 4 weeks for both groups. In addition, the group assigned to combination therapy received bupropion, which was started at 100 mg/day, with an increase to 200 mg/day after 2 weeks. Zonisamide was administered at night and bupropion in the morning. Body weight in kilograms was the primary outcome measure. RESULTS In an intent-to-treat analysis, carrying the last observation forward for all randomly assigned participants with at least 1 postbaseline assessment, the combination group lost more body weight than the zonisamide group (mean [SE] = 7.2 [1.2] kg [7.5%] vs. 2.9 [0.7] kg [3.1%]; F = 4.7, df = 4,56; p = .003) during the 12-week period. For the subset of 12 patients (combination, N = 7; zonisamide, N = 5) that completed the full 12-week treatment, the mean (SE) weight loss was 8.1 (1.4) kg (8.5%) for the combination group versus 3.0 (0.9) kg (3.3%) for the zonisamide group (F = 4.6, df = 4,40; p = .004). Six subjects in the combination group and 2 in the zonisamide group lost at least 5% of body weight. CONCLUSION In this short-term, open-label, preliminary trial, combination treatment of zonisamide and bupropion resulted in more weight loss than treatment with zonisamide alone.