Brain Over Bladder: A Systematic Review of Dual Cholinesterase Inhibitor and Urinary Anticholinergic Use

Case reports have demonstrated that dual use of cholinesterase inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be associated with delusions, aggression, changes in cognition, and anxiety, which typically resolve on drug discontinuation. Despite opposing mechanisms of action, these drugs continue to be co-prescribed.

This systematic review evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and describes its prevalence.

A literature search using terms related to ChIs and UAChs was conducted. Observational or interventional studies evaluating cognitive or functional outcomes in subjects receiving dual therapy were included for the primary aim. Articles describing prevalence of dual use were included for the secondary aim.

Of 1340 unique results, five studies met the inclusion criteria for the primary aim. Four of the studies assessed cognitive outcomes-three failed to identify a significant difference in cognitive function with dual use and the fourth study observed a statistically significant improvement in cognition with dual use of high-dose donepezil and solifenacin when compared with baseline. Three studies assessed functional outcomes-one revealed a 50% greater quarterly decline in activities of daily living (p = 0.01) among dual users functioning in the top quartile, another revealed significant functional improvement in dual users, and the final study did not demonstrate a significant difference. Seventeen articles were included for the secondary aim. Prevalence of dual use ranged from 1.2 to 40.5%.

This systematic review revealed a high prevalence of dual use of ChIs and UAChs; however, there are mixed results for cognitive and functional outcomes. Results were limited by methodological flaws. Observational or interventional studies assessing dual users are lacking and further study of cognitive and functional risks of dual ChI and UACh use is needed.