The risk of delirium and falls or fractures with the use of overactive bladder anticholinergic medications

Abstract

Objective: To determine if OAB anticholinergics have an increased risk of delirium or falls/fractures relative to OAB beta-3 agonist medications. Methods: This was a retrospective, cohort study using linked administrative data from the universal healthcare system of Ontario, Canada. Participants were all residents >66 years of age who newly initiated an OAB medication between January 2016 and March 2020. Coprimary outcomes were evidence of a hospital visit with delirium, or for a fall/fracture. We used matching weights to make the three exposure groups (beta-3 agonist, oxybutynin, or newer OAB anticholinergics) comparable across 82 baseline characteristics. We examined both the risk during the first 30 days (logistic regression) and the risk during continuous usage (proportional hazards).Results: We identified 103 024 older adults who started OAB medications. With matching weights, all measured variables were similar. The 30-day incidence of delirium was 0.31%, and fall/fracture was 1.07%; there was no significantly increased risk of either delirium (oxybutynin users OR 1.28 [95% CI 0.84-1.96], newer OAB anticholinergic users OR 0.92 [95% CI 0.58-1.46]) or falls/fractures (oxybutynin users OR 1.19 [95% CI 0.95-1.49], newer OAB anticholinergic users OR 1.14 [95% CI 0.91-1.43]) compared to beta-3 agonist users. With continuous usage, there was an increased HR of delirium among users of newer anticholinergics (HR 1.13, 95% CI 1.02-1.26) and an increased HR for fall/fracture among oxybutynin users (HR 1.13, 95% CI 1.02-1.24).Conclusions: Compared to beta-3 agonists, the continuous use of oxybutynin is associated with a significantly increased risk of fall/fracture, and newer OAB anticholinergics are associated with a significantly increased risk of delirium.

Probing polypharmacy, ageing and sex effects on physical function using different tests

“…53 Additionally, the central effects of oxycodone, oxybutynin and/or citalopram, may reduce balance beam performance through various mechanisms including sedation. [54][55][56] Age and sex differences in pharmacokinetics and pharmacodynamics may contribute to the differences in polypharmacy effects seen between groups. 57 Despite being genetically identical and receiving the same food, water and environmental conditions, there was individual variability in the performance of inbred mice in the same subgroup.…”

“…Beta‐blockers in high doses, compared with low doses and no medication, increase muscle fatiguability in humans 52 and also show no effects on knee extensors and handgrip muscle strength in healthy participants 53 . Additionally, the central effects of oxycodone, oxybutynin and/or citalopram, may reduce balance beam performance through various mechanisms including sedation 54–56 . Age and sex differences in pharmacokinetics and pharmacodynamics may contribute to the differences in polypharmacy effects seen between groups 57 …”

Use of overactive bladder anticholinergic medications associated with falls leading to emergency department visits: results from the ADRED study

“…One might differentiate between selective (solifenacin, darifenacin) and non-selective (oxybutynin, tolterodine, trospium, and fesoterodine) anticholinergics supported by a study indicating a significant risk for non-selective anticholinergic in patients [ 27 , 28 ]. Also, the time of use might be of importance for the individual fall-risk, as some drugs could be expected to increase the fall-risk with continuous use [ 29 ]. The anticholinergic burden of overactive bladder anticholinergic medications is associated with cognitive decline and could be connected with different altered risks for falls in older adults per single drugs [ 30 ].…”

Mirabegron versus vibegron in previously untreated female patients with overactive bladder: A randomized, single‐clinic, open‐label trial

“…The population of Japan is aging at an unprecedented rate, with the percentage of elderly people in Japan exceeding that in all other countries 4 ; in 2021, 28.9% of the Japanese population was 65 years or older, while 14.9% were 75 years or older 4 . Furthermore, OAB is known to have a significant negative impact on quality of life (QoL) 5,6 in elderly individuals and is associated with increased risk of falls, 7 fractures with the use of anticholinergics, 8 depression, 9 and sleep disturbances 10,11 …”