title: Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial.
abstract: OBJECTIVE
  Binge-eating disorder (BED), a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome, lacks approved pharmacotherapies.
  
  
  OBJECTIVE
  To examine the efficacy and safety of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to severe BED.
  
  
  METHODS
  We performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively.
  
  
  METHODS
  Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2) days after the last dose.
  
  
  METHODS
  We assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1. Secondary measures included BE cessation for 4 weeks. Safety assessments included treatment-emergent adverse events, vital signs, and change in weight.
  
  
  RESULTS
  At week 11, log-transformed BE days per week decreased with the 50-mg/d (least squares [LS] mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change, -1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group. Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively. The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3%) compared with the 50-mg/d (42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence of any treatment-emergent adverse events was 58.7% for the placebo group and 84.7% for the combined treatment group. In the treatment groups, 1.5% of participants had serious treatment-emergent adverse effects. Events with a frequency of at least 5% and changes in heart rate were generally consistent with the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups, respectively (P < .001 for each dose vs placebo group comparison in post hoc analysis).
  
  
  CONCLUSIONS
  The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement. The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. Further investigation of lisdexamfetamine in BED is ongoing.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01291173.
authors.affiliation: Research Institute, Lindner Center of HOPE, Mason, Ohio2Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: Department of Psychiatry, McLean Hospital/Harvard Medical School, Belmont, Massachusetts.
authors.forename: James I
authors.initials: JI
authors.lastname: Hudson
authors.affiliation: Neuropsychiatric Research Institute, Fargo, North Dakota5Department of Neuroscience, University of North Dakota School of Medicine, Fargo.
authors.forename: James E
authors.initials: JE
authors.lastname: Mitchell
authors.affiliation: Department of Psychology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Denise
authors.initials: D
authors.lastname: Wilfley
authors.affiliation: Shire, Wayne, Pennsylvania.
authors.forename: M Celeste
authors.initials: MC
authors.lastname: Ferreira-Cornwell
authors.affiliation: Shire, Wayne, Pennsylvania.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gao
authors.affiliation: Shire, Wayne, Pennsylvania8currently with CSL Behring, King of Prussia, Pennsylvania.
authors.forename: Jiannong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shire, Wayne, Pennsylvania.
authors.forename: Timothy
authors.initials: T
authors.lastname: Whitaker
authors.affiliation: Shire, Wayne, Pennsylvania9currently with Sage Therapeutics, Cambridge, Massachusetts.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jonas
authors.affiliation: Shire, Wayne, Pennsylvania.
authors.forename: Maria
authors.initials: M
authors.lastname: Gasior
mesh_terms: D000328:Adult; D056912:Binge-Eating Disorder / Q000188:drug therapy*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018765:Dopamine Uptake Inhibitors; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine