Prescribing cascades occur when cholinesterase inhibitor (ChEI)-induced urinary incontinence is misinterpreted as a new condition, leading to overactive bladder (OAB) antimuscarinic initiation. We evaluated whether the ChEI-OAB antimuscarinic prescribing cascade was associated with delirium or falls compared with mirabegron in older adults living with dementia.
We conducted a retrospective cohort study using the Anlitiks All-Payor Claims database (2015-2020). Participants were adults aged ≥ 65 years with dementia newly prescribed a ChEI with no prior ChEI or OAB therapy (180 days). A 60-day window identified OAB treatment initiation after ChEI therapy. Exposures were OAB antimuscarinics or mirabegron. Outcomes were incident delirium and falls identified using diagnosis codes. Propensity score-based weighting balanced baseline characteristics.
Among 2693 patients (mean age 80 years; 66.3% female), 201 (7.5%) initiated antimuscarinics and 2492 (92.5%) started mirabegron. Over 1 year, 8 (4.0%) antimuscarinic users developed delirium versus 95 (3.8%) mirabegron users (adjusted HR 1.35; 95% CI, 0.64-2.86). Falls occurred in 3 (1.5%) antimuscarinic users and 63 (2.5%) mirabegron users (adjusted HR 0.66; 95% CI, 0.20-2.15).
In older adults living with dementia, the estimated association between initiation of OAB antimuscarinics following ChEIs and the risks of delirium or falls, compared with mirabegron, was statistically compatible with benefit, harm, or no clinically meaningful difference. These findings highlight the need to evaluate whether OAB antimuscarinics are prescribed in response to true clinical need or as part of a prescribing cascade. Given the limited number of outcome events and resulting wide 95% CIs, future studies are needed to more precisely estimate the risk.
Key points ○ This study used an administrative claims database to evaluate, for the first time, the real‐world outcomes of the specific cholinesterase inhibitor–antimuscarinic prescribing cascade. ○ Among older adults (≥ 65 years) living with dementia newly prescribed cholinesterase inhibitors (ChEIs), a subset developed potential prescribing cascades, receiving overactive bladder (OAB) antimuscarinics soon after ChEI initiation. ○ Within 1 year of follow‐up, our study estimates suggested no clear association between the prescribing cascade and the risk of delirium and falls. ○ Larger studies with greater statistical power are needed to improve precision, better characterize these associations, and inform safer prescribing practices in this population. Why does this paper matter? ○ Prescribing cascades represent an important challenge in primary care and geriatric practice, particularly among patients with dementia who are highly vulnerable to adverse drug events. ○ This study addresses the clinical relevance of a well‐recognized prescribing cascade due to ChEI‐induced incontinence, leading to antimuscarinic therapy in a real‐world dementia population. ○ Findings were inconclusive, with effect estimates compatible with benefit, harm, or no clinically meaningful difference in the risk of delirium or fall. ○ However, given the modest effect estimates and associated uncertainty, additional research utilizing larger datasets to provide more stable estimates and corroborate our findings are warranted. ○ In addition, careful clinical assessment remains essential to ensure OAB antimuscarinics are prescribed for true therapeutic need rather than as a reactive prescribing cascade.
Journal of the American Geriatrics Society. 2026 Mar 15 [Epub ahead of print]
Sarah Beth Tucker, Bryan L Love, Chijioke M Okeke, Erin D Zwick, Chengwen Teng, Jingkai Wei, Ibraheem M Karaye, Saud Alsahali, Krithika Rajagopalan, Ismaeel Yunusa
Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina, Columbia, South Carolina, USA., Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, Texas, USA., Anlitiks Inc., Windermere, Florida, USA., Department of Family and Community Medicine, University of Texas Health Science Center, Houston, Texas, USA., Department of Anesthesiology, Montefiore Medical Canter/Albert Einstein College of Medicine, Bronx, New York, USA., Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraidah, Qassim, Saudi Arabia.