Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial

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11 Scopus citations


Background/Objectives: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). Design: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. Setting: Four memory care practices within four healthcare systems in the greater Indianapolis area. Participants: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. Intervention: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. Measurements: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. Results: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P =.063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. Conclusions: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. Trial Registration: NCT01362686 (

Original languageEnglish (US)
Pages (from-to)1497-1504
Number of pages8
JournalJournal of the American Geriatrics Society
Issue number7
StatePublished - Jul 2017


  • Alzheimer's
  • clinical care
  • dementia

ASJC Scopus subject areas

  • Geriatrics and Gerontology

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