Lisdexamfetamine for binge eating disorder in adults: a systematic review of the efficacy and safety profile for this newly approved indication - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

Objective: To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED).

Data sources: The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrials.gov and http://www.clinicaltrialsregister.eu for the search terms 'lisdexamfetamine' and 'binge', and by also querying the Web of Science (Thomson Reuters) and Embase (Elsevier) commercial databases, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.

Study selection: All available clinical reports of studies were identified.

Data extraction: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.

Data synthesis: LDX is a central nervous system stimulant indicated for the treatment of moderate to severe BED. The recommended dose range is 50-70 mg/day. Approval for the treatment of BED was based on a clinical development programme that included an 11-week Phase II proof-of-concept, placebo-controlled study, testing fixed doses of LDX 30, 50 and 70 mg/day, and two 12-week Phase III placebo-controlled studies examining LDX 50-70 mg/day. Statistically significant reductions in binge eating days/week, the primary outcome measure, were observed for LDX doses of 50 and 70 mg/day, with effect sizes in the Phase III trials ranging from 0.83 to 0.97. The pooled NNT for response across all trials (as defined by a Clinical Global Impressions-Improvement score of 'very much improved' or 'much improved') for LDX vs. placebo was 3 (95% CI 3-4), and NNT for remission (as defined by 4-week cessation of binge eating) for LDX vs. placebo was 4 (95% CI 4-6). Reductions in weight ranged between 5.2% and 6.25% for LDX 50 or 70 mg/day. Discontinuation rates because of adverse events (AEs) were low; NNH for discontinuation because of an AE for LDX vs. placebo was 44 (95% CI 23-1971). The most commonly encountered AEs (incidence ≥ 10% and greater than the rate for placebo) were dry mouth, decreased appetite, insomnia and headache, with NNH values vs. placebo of 4 (95% CI 3-5), 11 (95% CI 8-17), 11 (95% CI 8-18) and 19 (95% CI 11-75), respectively.

Conclusions: LDX is the first pharmacological agent that has received regulatory approval for the treatment of BED. LDX 50 or 70 mg/day significantly reduced BED symptoms as measured by the number of binge eating days per week. Effect sizes were highly robust. Pending clinical trials include a long-term study examining maintenance of efficacy.