title: Cholinesterase inhibitor discontinuation in patients with Alzheimer's disease: a meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  This meta-analysis examined the effects of cholinesterase inhibitor (ChEI) discontinuation in patients with Alzheimer's disease (AD).
  
  
  METHODS
  Electronic records up to March 2014 were searched from MEDLINE, Embase, PsycINFO, Cochrane Library, Allied and Complementary Medicine Database, and Cumulative Index to Nursing and Allied Health Literature. Search terms included Alzheimer's disease and cholinesterase inhibitors, plus discontinuation or cessation or tapering or withdrawal. There were no language limits.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled studies investigating the effect of ChEI discontinuation on patients with AD according to standardized criteria (eg, National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association, DSM-IV) and presenting measurable results of neuropsychological testing were included.
  
  
  METHODS
  Demographics, setting, ChEI treatment length, discontinuation protocol, follow-up duration, study outcomes, and dropouts during the double-blind phase were extracted.
  
  
  RESULTS
  Of 1,430 records returned, 18 were reviewed. Five ChEI discontinuation randomized controlled trials (N = 321 continued and N = 332 discontinued, following patients for 1.5-24 months) were analyzed. Discontinued patients demonstrated a significant worsening of cognition (standard mean Mini-Mental State Examination difference: -0.29 [95% CI, -0.45 to -0.13], N = 300 continued/307 discontinued, P < .001), a significant worsening of neuropsychiatric symptoms (standard mean Neuropsychiatric Inventory difference: -0.32 [-0.51 to -0.12], N = 199/211, P = .001), and significantly higher dropout rates (risk ratio [RR] = 1.33 [1.11-1.59], N = 321/332, P = .002) compared to those who continued. No difference in adverse events was observed (RR = 1.01 [0.85-1.20], N = 314/326, P = .92).
  
  
  CONCLUSIONS
  ChEI discontinuation may have negative effects on cognition and neuropsychiatric symptoms, a finding corroborated by a higher incidence of trial dropout.
authors.affiliation: Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.|Departments of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jordana
authors.initials: J
authors.lastname: O'Regan
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
authors.forename: Graham
authors.initials: G
authors.lastname: Mazereeuw
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D016032:Randomized Controlled Trials as Topic
chemical_list: D002800:Cholinesterase Inhibitors