HOLLYWOOD, FLA. – Not a single medication is approved for treatment of binge-eating disorder, but that could change if the favorable results of an ongoing phase III randomized trial of lisdexamfetamine mirror those of a recently completed phase II study.
Binge-eating disorder (BED) is the most common eating disorder. It is characterized by excessive food intake accompanied by psychological distress, but without the purging or fasting that are the hallmarks of bulimia nervosa and anorexia nervosa, respectively. Patients with BED are often severely obese, depressed, and have metabolic disorders.
Dr. Susan L. McElroy
BED is "gaining increasing recognition as a very significant public health problem, but it remains underdiagnosed," Dr. Susan L. McElroy observed at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
She presented the results of a 31-site, randomized, double-blind, placebo-controlled clinical trial of lisdexamfetamine (Vyvanse) in 213 patients with moderate or severe BED as defined by DSM-IV-TR. The study, in which participants recorded their binge-eating episodes in a daily diary, entailed a 2-week baseline period, 11 weeks of double-blind therapy, and a 1-week follow-up phase.
Patients were assigned to placebo or to lisdexamfetamine at 30, 50, or 70 mg/day. This was a forced-dose titration study. Everyone assigned to lisdexamfetamine started at 30 mg/day. After week 1, patients assigned to 50 or 70 mg/day increased their daily dose by 20 mg/wk until reaching their target.
Subjects assigned to lisdexamfetamine at 50 mg/day had a mean baseline of 4.54 binge-eating days/wk. By week 11 on the drug, this had improved to 0.31 days/wk.
This was a significantly better result than in placebo-treated controls, who went from 4.29 binge-eating days per week at baseline to 1.13 per week after 11 weeks. Patients assigned to lisdexamfetamine at 70 mg/day did best of all, improving from 4.47 binge-eating days/wk at baseline to 0.11 after 11 weeks.
In addition, 67% of patients in the 70-mg/day group had been free of any binge-eating episodes for 1 week at week 11, compared with 56% of subjects on lisdexamfetamine at 50 mg/day and 34% on placebo. These differences were statistically significant.
This was a dose-ranging study, and indeed a linear dose-response relationship was found. The 30-mg/day dose was not more effective than placebo. Using statistical analysis, the minimum effective dose of lisdexamfetamine for treatment of BED was estimated at 34 mg/day, said Dr. McElroy, chief research officer at the Lindner Center of HOPE in Mason, Ohio, and professor of psychiatry and behavioral neuroscience at the University of Cincinnati.
Lisdexamfetamine is a d-amphetamine prodrug that inhibits dopamine reuptake and stimulates release of monoamine neurotransmitters. The therapeutic rationale for its use in BED lies in the observation that BED is associated with abnormal signaling by the dopamine and norepinephrine neurotransmitter systems, she explained.
The drug’s approved indication is for treatment of attention-deficit/hyperactivity disorder, for which the recommended starting dose is 30 mg/day, with adjustments up to 70 mg/day permitted.
The side effects noted in the phase II BED study were typical of those seen when lisdexamfetamine is prescribed for ADHD.
This study was sponsored by Shire. Dr. McElroy is a consultant to or a member of the scientific advisory boards of Shire and a half-dozen other pharmaceutical companies.