title: Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis.
abstract: OBJECTIVE
  The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT).
  
  
  METHODS
  Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18-59 years, clinically definite multiple sclerosis (MS), and performance ≤ ½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participant's impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician's impression of memory change.
  
  
  RESULTS
  A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinician's impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed.
  
  
  CONCLUSIONS
  Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study.
  
  
  METHODS
  This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average.
authors.affiliation: Department of Neurology, State University of New York at Stony Brook, Stony Brook, NY 11794-8121, USA. lauren.krupp@stonybrook.edu
authors.forename: L B
authors.initials: LB
authors.lastname: Krupp
authors.forename: C
authors.initials: C
authors.lastname: Christodoulou
authors.forename: P
authors.initials: P
authors.lastname: Melville
authors.forename: W F
authors.initials: WF
authors.lastname: Scherl
authors.forename: L-Y
authors.initials: LY
authors.lastname: Pai
authors.forename: L R
authors.initials: LR
authors.lastname: Muenz
authors.forename: D
authors.initials: D
authors.lastname: He
authors.forename: R H B
authors.initials: RH
authors.lastname: Benedict
authors.forename: A
authors.initials: A
authors.lastname: Goodman
authors.forename: S
authors.initials: S
authors.lastname: Rizvi
authors.forename: S R
authors.initials: SR
authors.lastname: Schwid
authors.forename: B
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: H J
authors.initials: HJ
authors.lastname: Westervelt
authors.forename: H
authors.initials: H
authors.lastname: Wishart
mesh_terms: D000293:Adolescent; D000328:Adult; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D014706:Verbal Learning / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil