Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial.
ABSTRACT 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 zonisa-mide in the treatment of BED associated with obesity.
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.
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).
Zonisamide was efficacious, but not well tolerated, in the short-term treatment of BED associated with obesity.
ClinicalTrials.gov identifier NCT00221442.
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ABSTRACT: Introduction: This study evaluated controlled treatment studies of pharmacotherapy for binge eating disorder (BED). Areas covered: The primary focus of the review was on Phase II and III controlled trials testing medications for BED. A total of 46 studies were considered and 26 were reviewed in detail. BED outcomes included binge eating remission, binge eating frequency, associated eating disorder psychopathology, associated depression and weight loss. Expert opinion: Data from controlled trials suggest that certain medications are superior to placebo for stopping binge eating and for producing faster reductions in binge eating, and - to varying degrees - for reducing associated eating disorder psychopathology, depression and weight loss over the short term. Almost no data exist regarding longer-term effects of medication for BED. Except for topiramate, which reduces both binge eating and weight, weight loss is minimal with medications tested for BED. Psychological interventions and the combination of medication with psychological interventions produce binge eating outcomes that are superior to medication-only approaches. Combining medications with psychological interventions does not significantly enhance binge eating outcomes, although the addition of certain medications enhances weight losses achieved with cognitive-behavioral therapy and behavioral weight loss, albeit modestly.Expert Opinion on Emerging Drugs 01/2014; DOI:10.1517/14728214.2014.879291 · 3.28 Impact Factor
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ABSTRACT: The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing.Journal of Clinical Psychopharmacology 11/2014; 35(1). DOI:10.1097/JCP.0000000000000246 · 3.76 Impact Factor
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ABSTRACT: The aim of this study was to gain further understanding of placebo response in binge eating disorder. We pooled participant-level data from 10 double-blind, placebo-controlled, randomized trials of medications for binge eating disorder. The primary outcomes were response (75% reduction in binge eating episodes), cessation of binge eating episodes, change in mean weekly binge eating episodes and binge eating episodes per week. Of 234 participants receiving placebo, 89 (38%) were responders and 59 (26%) attained cessation. Placebo-treated participants significantly reduced their binge eating. The mean (SD) binge eating episodes per week at baseline was 5.2 (3.2) and at endpoint was 2.2 (2.6). Lower baseline binge eating episode frequency and longer study participation were significantly associated with response and cessation. Less severe eating pathology at baseline was associated with higher placebo response and cessation rates. Future clinical trials may want to stipulate that participants exceed a threshold of illness severity, which may lead to better placebo and drug separation. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.European Eating Disorders Review 03/2014; 22(2). DOI:10.1002/erv.2277 · 1.38 Impact Factor