title: The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease: a Bayesian network meta-analysis.
abstract: BACKGROUND
  Comparative evidence for efficacy and safety of second-generation cholinesterase inhibitors (ChEIs) is still sparse.
  
  
  OBJECTIVE
  The purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild-to-moderate Alzheimer's disease (AD).
  
  
  METHODS
  We conducted a systematic review for published articles and included randomised, double-blind, placebo-controlled trials and head-to-head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta-analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions.
  
  
  RESULTS
  Among the 21 trials included, network meta-analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS-Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety.
  
  
  CONCLUSIONS
  Our analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild-to-moderate AD.
authors.affiliation: Evidence Generation Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Evidence Generation Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Evidence Generation Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Nakagawa
authors.affiliation: Evidence Generation Department, Medical Affairs Division, Janssen Pharmaceutical K.K., Tokyo, Japan.
authors.forename: Kazutake
authors.initials: K
authors.lastname: Yoshizawa
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000544:Alzheimer Disease / Q000188:drug therapy; D001499:Bayes Theorem; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects; D000077265:Donepezil; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068836:Rivastigmine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D002800:Cholinesterase Inhibitors; D000077265:Donepezil; D005702:Galantamine; D007189:Indans; D010880:Piperidines; D000068836:Rivastigmine
keywords: Alzheimer's disease; cholinesterase inhibitors; meta-analysis