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

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.