Combination Therapy of Zonisamide and Bupropion for Weight Reduction in Obese Women: A Preliminary, Randomized, Open-Label Study

Kishore M. Gadde, M.D.; Gretchen M. Yonish, R.D.; Mariko S. Foust, R.D.; and H. Ryan Wagner II, Ph.D.

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/m²) 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.

(J Clin Psychiatry 2007;68:1226-1229)

Received July 15, 2006; accepted Nov. 27, 2006. From the Obesity Clinical Trials Program, Duke University Medical Center, Durham, N.C.

There was no external funding for this research.

Dr. Gadde has received research support from the National Institute of Diabetes and Digestive and Kidney Diseases, GlaxoSmithKline, Elan, Johnson & Johnson, Eli Lilly, and Vivus; has served as a consultant for Orexigen, GlaxoSmithKline, and Vivus; and owns stock in Orexigen Therapeutics. Duke University was awarded U.S. patent 7,109,198 for this combination therapy in September 2006 titled "Method for Treating Obesity" with Dr. Gadde as an inventor; Duke University has licensed this invention to Orexigen. Ms. Yonish, Ms. Foust, and Dr. Wagner report no additional financial affiliations or other relationships relevant to the subject of this article.

Corresponding author and reprints: Kishore M. Gadde, M.D., Box 3292, Duke University Medical Center, Durham, NC 27710 (e-mail: gadde001@mc.duke.edu).