title: Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States.
  
  
  METHODS
  Four memory care practices within four healthcare systems in the greater Indianapolis area.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686).
authors.affiliation: Department of Pharmacy Practice, Purdue University School of Pharmacy, West Lafayette, Indiana.|Indiana University Center for Aging Research, Indianapolis, Indiana.|Regenstrief Institute, Inc., Indianapolis, Indiana.|Eskenazi Health, Indianapolis, Indiana.
authors.forename: Noll L
authors.initials: NL
authors.lastname: Campbell
authors.affiliation: Center for Healthcare Innovation and Implementation Science, Indianapolis, Indiana.|Indiana Clinical and Translational Sciences Institute, Indianapolis, Indiana.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Perkins
authors.affiliation: Indiana University Center for Aging Research, Indianapolis, Indiana.|Regenstrief Institute, Inc., Indianapolis, Indiana.|Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.affiliation: Indiana University Center for Aging Research, Indianapolis, Indiana.|Regenstrief Institute, Inc., Indianapolis, Indiana.|Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Hugh C
authors.initials: HC
authors.lastname: Hendrie
authors.affiliation: Indiana University Center for Aging Research, Indianapolis, Indiana.|Regenstrief Institute, Inc., Indianapolis, Indiana.|Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Nicole
authors.initials: N
authors.lastname: Fowler
authors.affiliation: Indiana University Center for Aging Research, Indianapolis, Indiana.|Regenstrief Institute, Inc., Indianapolis, Indiana.|Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Callahan
authors.affiliation: Indiana University Center for Aging Research, Indianapolis, Indiana.|Regenstrief Institute, Inc., Indianapolis, Indiana.|Center for Healthcare Innovation and Implementation Science, Indianapolis, Indiana.|Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Malaz A
authors.initials: MA
authors.lastname: Boustani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000208:ethnology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D000077265:Donepezil; D016527:Drug Costs; D064420:Drug-Related Side Effects and Adverse Reactions; D005006:Ethnicity; D005260:Female; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D007196:Indiana; D008297:Male; D055118:Medication Adherence; D010880:Piperidines / Q000627:therapeutic use; D000068836:Rivastigmine / Q000627:therapeutic use
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine
keywords: Alzheimer's; clinical care; dementia