title: Medication adherence and tolerability of Alzheimer's disease medications: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  The class of acetylcholinesterase inhibitors (ChEI), including donepezil, rivastigmine, and galantamine, have similar efficacy profiles in patients with mild to moderate Alzheimer's disease (AD). However, few studies have evaluated adherence to these agents. We sought to prospectively capture the rates and reasons for nonadherence to ChEI and determine factors influencing tolerability and adherence.
  
  
  METHODS
  We designed a pragmatic randomized clinical trial to evaluate the adherence to ChEIs among older adults with AD. Participants include AD patients receiving care within memory care practices in the greater Indianapolis area. Participants will be followed at 6-week intervals up to 18 weeks to measure the primary outcome of ChEI discontinuation and adherence rates and secondary outcomes of behavioral and psychological symptoms of dementia. The primary outcome will be assessed through two methods, a telephone interview of an informal caregiver and electronic medical record data captured from each healthcare system through a regional health information exchange. The secondary outcome will be measured by the Healthy Aging Brain Care Monitor and the Neuropsychiatric Inventory. In addition, the trial will conduct an exploratory evaluation of the pharmacogenomic signatures for the efficacy and the adverse effect responses to ChEIs. We hypothesized that patient-specific factors, including pharmacogenomics and pharmacokinetic characteristics, may influence the study outcomes.
  
  
  CONCLUSIONS
  This pragmatic trial will engage a diverse population from multiple memory care practices to evaluate the adherence to and tolerability of ChEIs in a real world setting. Engaging participants from multiple healthcare systems connected through a health information exchange will capture valuable clinical and non-clinical influences on the patterns of utilization and tolerability of a class of medications with a high rate of discontinuation.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT01362686.
authors.affiliation: Department of Pharmacy Practice, Purdue University School of Pharmacy, 410 West 10th Street, West Lafayette, IN, USA. campbenl@iupui.edu
authors.forename: Noll L
authors.initials: NL
authors.lastname: Campbell
authors.forename: Paul
authors.initials: P
authors.lastname: Dexter
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Perkins
authors.forename: Sujuan
authors.initials: S
authors.lastname: Gao
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.forename: Amie
authors.initials: A
authors.lastname: Frame
authors.forename: Hugh C
authors.initials: HC
authors.lastname: Hendrie
authors.forename: Chris M
authors.initials: CM
authors.lastname: Callahan
authors.forename: Malaz A
authors.initials: MA
authors.lastname: Boustani
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000523:psychology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002985:Clinical Protocols; D015897:Comorbidity; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007196:Indiana; D008297:Male; D055118:Medication Adherence; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010597:Pharmacogenetics; D019338:Polypharmacy; D011446:Prospective Studies; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents