CNS Drugs

, Volume 28, Issue 2, pp 157–170 | Cite as

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
  • Virginie GardetteEmail author
  • Maryse Lapeyre-Mestre
  • Antoine Piau
  • Adeline Gallini
  • Christelle Cantet
  • Jean-Louis Montastruc
  • Bruno Vellas
  • Sandrine Andrieu
  • The ICTUS Group
Original Research Article



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.


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).


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.


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.


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.


Memantine Rivastigmine Galantamine Unacceptable Adverse Event Stop Date 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank Nicola Coley for her revision of the manuscript.


The ICTUS study was partially supported by a grant from the European Commission within the 5th framework program (QLK6-CT-2002-02645) and partially from an unrestricted equal grant from each of Eisai, Janssen, Lundbeck and Novartis pharmaceutical companies. The pharmaceutical companies had no role in study design, data collection, data analysis, data interpretation or writing of the report.

Conflicts of interests

All the authors declare that they have no conflict of interest relevant to the content of this study. Prof. Andrieu has received grants from Beaufour, Ipsen, Lundbeck, Nestlé and Lilly; has consulted for Beaufour, Lundbeck, Lilly, Pfizer, Esai, Nestlé, Novartis, Roche, Sanofi, Pierre Fabre, Servier and Chiesi; has performed lectures for Beaufour, Esai, Pierre Fabre, Servier, Janssen, Pfizer, Lundbeck, Nestlé, Novartis and Chiesi; and has received fees for participation in review activities for Cure Huntington's Disease foundation. Prof. Vellas has received grants from BMS, Elan, Lilly, Medivation, Pfizer, Roche, GlaxoSmithKline and Wyeth, and is board member of Eisai, Elan, Exhonit, GlaxoSmithKline, Lilly, Medication, Nestlé, Nutricia, Pfizer, Pierre Fabre, Roche, Sanofi, Servier, Tau Rx Therapeutics, Wyeth and Astra. All other authors declare that they have no conflict of interest.

Supplementary material

40263_2013_133_MOESM1_ESM.docx (40 kb)
Supplementary Table 1 (DOCX 39 kb)


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Virginie Gardette
    • 1
    • 2
    • 3
    • 4
    • 7
    Email author
  • Maryse Lapeyre-Mestre
    • 1
    • 2
    • 3
    • 5
  • Antoine Piau
    • 3
    • 6
  • Adeline Gallini
    • 1
    • 2
    • 4
  • Christelle Cantet
    • 1
    • 2
    • 6
  • Jean-Louis Montastruc
    • 1
    • 2
    • 3
    • 5
  • Bruno Vellas
    • 1
    • 2
    • 3
    • 6
  • Sandrine Andrieu
    • 1
    • 2
    • 3
    • 4
  • The ICTUS Group
  1. 1.INSERM UMR1027ToulouseFrance
  2. 2.Faculté de Médecine Univ Toulouse IIIToulouseFrance
  3. 3.Gérontopôle, CHU ToulouseToulouseFrance
  4. 4.Epidemiology and Public Health DepartmentCHU ToulouseToulouseFrance
  5. 5.Pharmacology DepartmentCHU ToulouseToulouseFrance
  6. 6.Department of Internal Medicine and GeriatricsCHU ToulouseToulouseFrance
  7. 7.INSERM UMR1027, Faculté de Medecine, Université Paul SabatierToulouseFrance

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