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Clinical Research

What pharmacological interventions are effective in binge-eating disorder? Insights from a critical evaluation of the evidence from clinical trials

Abstract

Binge-eating disorder (BED) is the commonest eating disorder and an important causal factor in obesity. Lisdexamfetamine is the only approved pharmacological treatment. Many drugs have been clinically evaluated and several were described as potentially promising treatments. A comprehensive reassessment of the evidence from these clinical trials has been performed. The questions to be answered were: (1) Does the evidence support claims of efficacy? (2) What pharmacological mechanisms show promise for developing new BED drugs? (3) What are the clinical implications for treating BED? PubMed and internal database searches identified every available published drug trial in BED. The trials and their results were summarised and reviewed to re-evaluate the evidence. Factors taken into consideration included psychiatric diagnosis, primary endpoint, secondary outcome measures, trial size, blinding and controls, drop-out rates, placebo response rates and weight-loss. Drugs were classified according to their pharmacology and therapeutic indication to determine which mechanisms were effective and to provide insights into the psychopathology of BED. For most drugs, robust evidence of efficacy in BED is insubstantial or absent. Some catecholaminergic drugs developed for ADHD are also effective in BED; other pharmacological mechanisms are weakly efficacious at best. Reducing BED severity has little impact on weight. Conversely, weight-loss from anti-obesity therapy is ineffective in ameliorating the psychopathological drivers of BED. (1) BED is a psychiatric not a metabolic disorder. (2) Weight-loss drugs are generally ineffective in BED. (3) Efficacy in BED is restricted to powerful catecholaminergic drugs. (4) Drugs acting via noradrenaline, 5-HT, GABA, carbonic anhydrase inhibition, opioid receptors and various ion channels are generally minimally effective at best. (5) Efficacy in BED is dependent on treating its core psychopathology; reducing impulsivity and compulsivity and increasing cognitive restraint over eating. (6) Obese subjects with BED may benefit from separate treatments for these two disorders.

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Fig. 1: Comparison of the effects of lisdexamfetamine (LDX) and dasotraline on the changes of binge-eating days/week (primary endpoint) and Y-BOCS-BE (Yale-Brown Obsessive Compulsive Scale modified for Binge-Eating) scores (secondary end-point) in subjects with binge-eating disorder.
Fig. 2: Effects of lisdexamfetamine on the mean number of binge days/week and mean weight.
Fig. 3: Lack of an association between change in number of binge-eating days/week and percent change in body weight in subjects taking lisdexamfetamine or placebo.

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DJH and JG both participated in performing the research underpinning the content of the review and both authors contributed to the preparation of the manuscript

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DJ Heal and J Gosden are shareholders and employees of DevelRx Ltd. DevelRx provides consultancy to the pharmaceutical industry in a range of areas including the discovery and development of new drugs to treat binge-eating disorder. The authors received no external financial or logistical support when writing this manuscript. The opinions expressed are those of the authors and have not been influenced by any commercial organisation.

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Heal, D.J., Gosden, J. What pharmacological interventions are effective in binge-eating disorder? Insights from a critical evaluation of the evidence from clinical trials. Int J Obes 46, 677–695 (2022). https://doi.org/10.1038/s41366-021-01032-9

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