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

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: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686).