Zonisamide in the Treatment of Binge Eating Disorder With Obesity: A Randomized Controlled Trial

Susan L. McElroy, M.D.; Renu Kotwal, M.D.; Anna I. Guerdjikova, Ph.D.; Jeffrey A. Welge, Ph.D.; Erik B. Nelson, M.D.; Kathleen A. Lake, M.S.W.; David A. D'Alessio, M.D.; Paul E. Keck, Jr., M.D.; and James I. Hudson, M.D., Sc.D.

Objective: Binge eating disorder (BED) is associated with obesity. Zonisamide is a novel antiepileptic drug associated with weight loss. The purpose of this study was to evaluate zonisamide in the treatment of BED associated with obesity.

Method: In this 16-week, single-center, randomized, double-blind, placebo-controlled, flexible-dose (100-600 mg/day) trial, 60 outpatients with DSM-IV-TR BED received zonisamide (N = 30) or placebo (N = 30). The primary outcome measure was weekly frequency of binge eating episodes. The primary analysis of efficacy was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time interaction as the effect measure. Patients were enrolled from September 5, 2003, through October 1, 2004.

Results: Compared with placebo, zonisamide was associated with a significantly greater rate of reduction in binge eating episode frequency (p = .021), body weight (p < .001), BMI (p = .001), and scores on the Clinical Global Impressions-Severity scale (p < .001), Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating (p < .001), and Three Factor Eating Questionnaire disinhibition scales (p < .001). Plasma ghrelin concentrations increased with zonisamide but decreased with placebo (p = .001). The mean (SD) zonisamide daily dose at endpoint evaluation was 436 (159) mg/day. Twelve patients (N = 8 receiving zonisamide, N = 4 receiving placebo) discontinued because of adverse events. The most common reasons for discontinuing zonisamide were accidental injury with bone fracture (N = 2), psychological complaints (N = 2), and cognitive complaints (N = 2).

Conclusion: Zonisamide was efficacious, but not well tolerated, in the short-term treatment of BED associated with obesity.

Clinical Trials Registration: ClinicalTrials.gov identifier NCT00221442

(J Clin Psychiatry 2006;67:1897-1906)

Received April 6, 2006; accepted May 24, 2006. From the Psychopharmacology Research Program, Department of Psychiatry (Drs. McElroy, Kotwal, Guerdjikova, Welge, Nelson, and Keck and Ms. Lake) and the Division of Endocrinology, Department of Internal Medicine (Dr. D'Alessio), University of Cincinnati College of Medicine; and the General Clinical Research Center (Drs. D'Alessio and Keck) and the Mental Health Service Line (Dr. Keck), Cincinnati Veteran Affairs Medical Center, Cincinnati, Ohio; and the Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Mass. (Dr. Hudson).

This study was supported in part by a grant from Eisai Pharmaceuticals, Inc.

Financial disclosure appears at the end of this article.

Corresponding author and reprints: Susan L. McElroy, M.D., Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, P.O. Box 670559, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0559 (e-mail: susan.mcelroy@uc.edu).