title: Zonisamide for weight reduction in obese adults: a 1-year randomized controlled trial.
abstract: BACKGROUND
  Obese individuals who have failed to achieve adequate weight loss with lifestyle changes have limited nonsurgical therapeutic options. We evaluated the efficacy and tolerability of zonisamide, an antiepileptic drug, for enhancing weight loss in obese patients receiving diet and lifestyle guidance.
  
  
  METHODS
  This was a 1-year, randomized, double-blind, placebo-controlled trial conducted from January 9, 2006, through September 20, 2011, at Duke University Medical Center. A total of 225 obese (mean [SD] body mass index, 37.6 [4.9]) participants included 134 women (59.6%) and 91 men (40.4%) without diabetes mellitus. (Body mass index is calculated as weight in kilograms divided by height in meters squared.) Interventions were daily dosing with placebo (n = 74), 200 mg of zonisamide (n = 76), or 400 mg of zonisamide (n = 75), in addition to diet and lifestyle counseling by a dietitian for 1 year. Primary outcome was change in body weight at 1 year.
  
  
  RESULTS
  Of the 225 randomized patients, 218 (96.9%) provided 1-year follow-up assessments. Change in body weight was -4.0 kg (95% CI, -5.8 to -2.3 kg; least squares mean, -3.7%) for placebo, -4.4 kg (-6.1 to -2.6 kg; -3.9%; P = .79 vs placebo) for 200 mg of zonisamide, and -7.3 kg (-9.0 to -5.6 kg; -6.8%; P = .009 vs placebo) for 400 mg of zonisamide. In the categorical analysis, 23 (31.1%) assigned to placebo, 26 (34.2%; P = .72) assigned to 200 mg of zonisamide, and 41 (54.7%; P = .007) assigned to 400 mg of zonisamide achieved 5% or greater weight loss; for 10% or greater weight loss, the corresponding numbers were 6 (8.1%), 17 (22.4%; P = .02), and 24 (32.0%; P < .001). Gastrointestinal, nervous system, and psychiatric adverse events occurred at a higher incidence with zonisamide than with placebo.
  
  
  CONCLUSIONS
  Zonisamide at the daily dose of 400 mg moderately enhanced weight loss achieved with diet and lifestyle counseling but had a high incidence of adverse events.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00275834
authors.affiliation: Obesity Clinical Trials Program, Duke University Medical Center, Durham, NC 27710, USA. kishore.gadde@duke.edu
authors.forename: Kishore M
authors.initials: KM
authors.lastname: Gadde
authors.forename: Mariko F
authors.initials: MF
authors.lastname: Kopping
authors.forename: H Ryan
authors.initials: HR
authors.lastname: Wagner
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Yonish
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects*; D055815:Young Adult; D000078305:Zonisamide
chemical_list: D000975:Antioxidants; D007555:Isoxazoles; D000078305:Zonisamide