title: Lisdexamfetamine in the treatment of moderate-to-severe binge eating disorder in adults: systematic review and exploratory meta-analysis of publicly available placebo-controlled, randomized clinical trials.
abstract: BACKGROUND
  Preliminary placebo-controlled evidence paved the ground to the US Food and Drug Administration approval extension of lisdexamfetamine for the treatment of moderate-to-severe binge eating disorder (BED) in adults.
  
  
  OBJECTIVE
  To provide a preliminary qualitative and quantitative synthesis of the placebo-controlled, randomized clinical trials (RCTs) considering the efficacy and tolerability of lisdexamfetamine in the acute and/or maintenance treatment of moderate-to-severe BED in adults.
  
  
  METHODS
  A preliminary, yet comprehensive, systematic review was performed by accessing a broad range of resources providing publicly available data about lisdexamfetamine at the time of inquiry (March 2016). Study eligibility criteria, participants, and interventions were considered focusing on major clinical and functional outcomes of either efficacy or tolerability of lisdexamfetamine in the treatment of moderate-to-severe BED in adults.
  
  
  RESULTS
  Meta-analysis of data pooled from three acute RCTs significantly favored lisdexamfetamine over placebo in the reduction of binge eating days/week, Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating total score, weight, response, and remission rates (all, P≤0.01). In contrast, discontinuation rates due to treatment-emergent adverse events were significantly higher among patients in receipt of lisdexamfetamine (relative risk 2.19, P=0.04) versus placebo.
  
  
  CONCLUSIONS
  Publication, selection, performance, attrition, reporting, sponsorship, and "diagnostic shift" biases. Lack of inclusion of adverse event effects other than those requiring discontinuation of the trial(s), as well as lack of information about clinically relevant psychiatric or other medical comorbidities, limits the overall generalizability of pooled results.
  
  
  CONCLUSIONS
  Across the included acute phase RCTs, lisdexamfetamine (at 30, 50, or 70 mg/day) led to significant reduction in a number of clinically relevant outcomes compared to placebo. Moreover, safety concerns related to adverse events, high discontinuation rates, and the need for additional long-term maintenance of RCTs solicit careful monitoring of the drug in terms of overall safety and tolerability by further RCTs.
authors.affiliation: New York State Psychiatric Institute, Columbia University, New York City, NY, USA; Polyedra Research Group, Ascoli.
authors.forename: Michele
authors.initials: M
authors.lastname: Fornaro
authors.affiliation: Department of Neurosciences, University of Padua; Department of Mental Health, National Health Service, Padova; IREM Institute for Clinical Research and Education in Medicine, Padova.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Polyedra Research Group, Ascoli; Department of Clinical Neurosciences, Hermanas Hospitalarias - Villa San Benedetto Menni Hospital, FoRiPsi, Albese con Cassano, Como.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Perna
authors.affiliation: Polyedra Research Group, Ascoli; Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, National Health Service, Hospital "G Mazzini", Teramo.
authors.forename: Domenico
authors.initials: D
authors.lastname: De Berardis
authors.affiliation: IREM Institute for Clinical Research and Education in Medicine, Padova; Department of Medicine (DIMED), University of Padua, Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Polyedra Research Group, Ascoli; Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Orsolini
authors.affiliation: New York State Psychiatric Institute, Columbia University, New York City, NY, USA; Department of Psychiatry, School of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Licinia
authors.initials: L
authors.lastname: Ganança
authors.affiliation: Department of Health Service and Population Research, Institute of Psychiatry, King's College London; Department of Physiotherapy, South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
keywords: binge eating disorder; lisdexamfetamine; meta-analysis; systematic review