title: A 2-year prospective cohort study of antidementia drug non-persistency in mild-to-moderate Alzheimer's disease in Europe : predictors of discontinuation and switch in the ICTUS study.
abstract: BACKGROUND
  There is no consensus on when and how to discontinue cholinesterase inhibitors (ChEI). Predictors of non-persistency of antidementia drugs have been poorly investigated, mostly during short-term periods and using administrative data.
  
  
  OBJECTIVE
  The aim of this study was to investigate the incidence and predictors of ChEI switch and discontinuation among subjects with ascertained Alzheimer's disease (AD).
  
  
  METHODS
  A total of 557 community-dwelling, mild-to-moderate AD subjects initiating ChEIs in 29 European clinic centres were assessed twice-yearly for 2 years. Antidementia drug exposure was recorded through a physician-administered structured questionnaire to document any change in drug therapy (start and stop dates, reasons). Discontinuation was defined as >35 days without any antidementia drug. Switch was defined as a change for any antidementia drug strategy within 35 days after ChEI cessation. Two separate time-dependent multivariate Cox survival analyses were conducted to identify predictors of discontinuation and switch.
  
  
  RESULTS
  The incidences of discontinuation and switch were 9.65 and 12.47/100 person-years, respectively. Behavioural disturbances, low body mass index, falls, decline in Mini-Mental State Examination (MMSE) score, and AD-related hospitalization predicted discontinuation. MMSE score, decline in activities of daily living score, aberrant motor behaviour, shorter AD duration and higher nurse resource use predicted a switch. An ineffective ChEI dose and clinic specialty predicted both outcomes. Sensitivity analyses using a 60-day cut-off provided stable results.
  
  
  CONCLUSIONS
  Several predictors were identified: adverse drug events and their predisposing factors, perceived loss of efficacy or disease progression on cognitive or functional scales, behavioural disturbances, hospitalization and professional practices. The latter implies a need for harmonization in AD drug prescription practice.
authors.affiliation: INSERM UMR1027, 31073, Toulouse, France, virginie.gardette@univ-tlse3.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Gardette
authors.forename: Maryse
authors.initials: M
authors.lastname: Lapeyre-Mestre
authors.forename: Antoine
authors.initials: A
authors.lastname: Piau
authors.forename: Adeline
authors.initials: A
authors.lastname: Gallini
authors.forename: Christelle
authors.initials: C
authors.lastname: Cantet
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.forename: Sandrine
authors.initials: S
authors.lastname: Andrieu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000453:epidemiology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009483:Neuropsychological Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012720:Severity of Illness Index; D016903:Drug Monitoring
chemical_list: D002800:Cholinesterase Inhibitors