Zonegran in the Treatment of Binge Eating Disorder Associated With Obesity
Condition: Binge Eating Disorder Associated With Obesity
MeSH terms: Obesity; Bulimia; Feeding and Eating Disorders; Binge-Eating Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      The specific aim of this study is to examine the efficacy and safety of zonisamide compared
      with placebo in outpatients with binge eating disorder associated with obesity.
    

Detailed description: 
      Binge eating disorder (BED) is characterized by recurrent, uncontrollable, and distressing
      episodes of excessive food consumption (binge eating) without compensatory weight loss
      behaviors.1,2 Its prevalence in the general population of the United States is conservatively
      estimated to be 1.5% to 2%,1-6 making it more common than anorexia nervosa and bulimia
      nervosa combined. BED is associated with being overweight and obesity.1-7 Approximately 8% to
      30% of those seeking standard weight loss treatments, 1-4 up to 50% of those seeking
      bariatric surgery,8,9 and 70% of those participating in Overeaters Annonymous3 are estimated
      to have BED.

      Zonisamide is a structurally and pharmacologically novel antiepileptic drug - a
      sulfamate-substituted monosaccharide - with proven anticonvulsant efficacy when used
      adjunctively in refractory partial epilepsy.10-12 Mechanisms hypothesized to account for
      zonisamide's antiepileptic properties include antagonism of voltage-gated sodium and T-type
      calcium channels, blockade of potassium-evoked glutamate release, modulation of central
      dopaminergic and serotonergic function, and carbonic anhydrase inhibition.10-16 Several lines
      of evidence suggest that zonisamide might be a useful treatment for BED. First, like the
      anticonvulsant topiramate,17-19 zonisamide has been associated with anorexia and weight loss
      in clinical trials in epilepsy patients10,11,20 and in patients with obesity.20 Topiramate
      has also been shown to reduce binge eating and weight in patients with binge eating disorder
      associated with obesity. 21 Although zonisamide and topiramate have distinct pharmacologic
      profiles, both drugs share several pharmacologic actions. These include sodium channel
      blockade, carbonic anhydrase inhibition, and reduction of glutamate neurotransmission.
      10,11,13,16,17 Regarding the latter property, animal studies have shown that stimulation of
      the lateral hypothalamus by glutamate and glutamate agonists causes an intense, rapid,
      dose-dependent increase in food intake,22 whereas glutamate antagonism of the nucleus tractus
      solitarius reduces food intake.23 Second, unlike topiramate, zonisamide also modulates the
      function of serotonin and dopamine14, 15 --two neurotransmitters involved in the regulation
      of feeding behavior24 and the mechanisms of some medications with efficacy in either binge
      eating (SSRIs, d-fenfluramine) 25-29 or obesity (sibutramine, stimulants).30 Third, a broad
      range of antidepressants have been reported to reduce binge eating in both bulimia nervosa31
      and binge eating disorder25-28,32 and preliminary observations suggest zonisamide may have
      thymoleptic properties.33,34 Fourth, in an open-label trial of zonisamide in 15 patients with
      BED conducted by our group, zonisamide was effective in reducing binge eating frequency,
      severity of illness, and weight (S.L. McElroy, J Clin Psychiatry, under review).35 We
      therefore propose to conduct a double-blind, placebo-controlled, randomized, parallel group,
      16-week study of zonisamide in 60 outpatients with binge eating disorder and obesity.
    

Intervention name(s): Zonegran; sugar pill
Intervention type(s): Drug; Drug
Intervention description(s): zonegran (zonisamide); fake pill
Intervention MeSH terms: Zonisamide
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Adults; Binge eating disorder; Blood draw; E.Coli enterprotoxin; Eating disorders; Electrocardiogram; Females; Males; Physical exam; Psychiatric evaluation; Questionnaire