Co-Prescribing of Medications with Anticholinergic Properties to Those Using Cholinesterase Inhibitors for Dementia

Abstract

Background: Medications with anticholinergic (AC) propertieshave adverse effects on cognition and many guidelines recommend avoiding them in older adults. Theoretically they could negate benefits of cholinesterase inhibitor (CI) treatment in patients dementia patients, although there is inadequate evidence to date. Objectives: To determine the frequency of AC medicine use in patients treated with a CI and to assess whether such use is associated with early CI discontinuation. Methods: A retrospective cohort study was carried out using the General Practice Research Database. Subjectswere all patients aged 18+ with a new CI prescription after January 2000. All medicines were classified as to their AC properties according to the Rudolph Anticholinergic Risk Scale. AC medication use in patients prescribed CI was determined as well as CI discontinuation rates in those with and without AC medicines. Cox regression survival analysis with time dependent covariates was carried out to determine risk factors for CI discontinuation. Results: 7523 patients newly prescribed CIs were identified. On average, CIs were prescribed for 536 days; 50% of users had discontinued treatment 383 days after CI initiation;75% had discontinued by day 777. 3556 (47%) patients used CIs and AC medicines concomitantly; 1946 (26%) for over 90 days. Being underweight and frail were associated with a 12–15% higher risk of CI discontinuation. An association was found between concomitant AC use (especially antipsychotics) and discontinuation of CI but no association with the strength of AC action or cumulative exposure. Patients aged 80+ were significantly more likely to discontinue their CI early: HRadj 1.27 (CI951.13–1.43) in 80–84 year olds and 1.72 (CI951.53–1.93) in those aged 85+. Conclusions: Further work is needed to evaluate any association between CI discontinuation and cumulative AC exposure. Very elderly and underweight patients discontinued CIs earlier.