title: Efficacy of memantine, donepezil, or their association in moderate-severe Alzheimer's disease: a review of clinical trials.
abstract: BACKGROUND
  Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild-moderate and moderate-severe forms of Alzheimer's disease (AD), respectively. High doses of the AChE-I donepezil were licensed in the USA for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage.
  
  
  OBJECTIVE
  This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD.
  
  
  METHODS
  Double-blind, placebo-controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate-severe AD were reviewed. Analysis done in January 2013 considered the years 2007-2012.
  
  
  CONCLUSIONS
  Only 83 of the 941 papers selected were considered relevant, and only 13 met the criterion of "adequacy and representativeness." Memantine and donepezil lead to improvements in moderate-to-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine-donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24-52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials.
authors.affiliation: Centro Ricerche Cliniche, Telemedicina e Telefarmacia, Università di Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Molino
authors.forename: Luisa
authors.initials: L
authors.lastname: Colucci
authors.forename: Angiola M
authors.initials: AM
authors.lastname: Fasanaro
authors.forename: Enea
authors.initials: E
authors.lastname: Traini
authors.forename: Francesco
authors.initials: F
authors.lastname: Amenta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy*; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D008559:Memantine