Anticholinergic use for 3 months or longer increases dementia risk by about 46%

Anticholinergic use for 3 months or longer increases dementia risk by about 46% compared with nonuse, according to a recent review and meta-analysis published in Neurourology and Urodynamics.¹ The investigators of the review saw a similar relationship with drugs many urologists use to treat overactive bladder.

According to study author Roger R. Dmochowski, MD, MMHC, professor of urologic surgery at Vanderbilt University Medical Center, the increased risk of incident dementia following anticholinergic agent use is not well known or understood. But he said that urologists and other prescribers, as well as patients, are becoming more aware of the risk. This paper sheds light on the significant separation in cognition and other central nervous system risks in patients taking anticholinergic medications versus those who are not, he said.

In the main analysis, the investigators did a systematic literature review and meta-analysis assessing the impact of 3 months or longer anticholinergic use on the risk of multiple subtypes of incident dementia. It also evaluated the association between drugs used to treat overactive bladder and dementia risk.

Although the electronic search revealed more than 2100 articles for the main analysis, only 6 studies met the inclusion criteria. These 6 papers assessed anticholinergic agent impact, reflecting outcomes for dementia subtypes, including Alzheimer disease, Lewy body dementia, vascular dementia, and others.

Across the 6 studies, the estimate of the average rate ratio for incident dementia ranged from 1.05 to 2.63. All but 1 of the studies reported an association.

Two studies in the meta-analysis looked specifically at the impact of overactive bladder medicines on dementia. Bladder antimuscarinics have high anticholinergic activity.

“The nested case-control studies by Coupland et al and Richardson et al reported an increased risk of dementia with [3 or more] months of use of bladder antimuscarinics (eg, darifenacin, fesoterodine, flavoxate, oxybutynin, propiverine, solifenacin, tolterodine, and trospium),” the investigators wrote. Adjusted odds ratios ranged from 1.35 to 1.65 and 1.21 to 1.35. The risk tended to be greater in higher exposure categories.^2,3 Dementia risk from overactive bladder medications was higher than the overall risk across anticholinergic agents for all total standardized daily doses and defined daily doses, the study authors continued.

According to Dmochowski, urologists most commonly use anticholinergics as a formulary-covered prescription, although increasingly, mail orders play a role.

“Patient access to these drugs is facilitated by a tiering system which places this class as first tier for most formularies,” he said.

According to the investigators, given the substantial increase in dementia risk associated with anticholinergic use, urologists and other prescribers should weigh potential risks and benefits before recommending these medications.

Dmochowski anticipates increasing concern among urologists and others when prescribing anticholinergics for overactive bladder and other indications. Prescribers already are thinking twice, he said.

“The risk appears to be summative, and again, urologists really need to be aware of this patient concern,” he said. “The drugs are used chronically; therefore, other drug classes such as the beta-3 agonists are the best pharmacologic option and should be used in conjunction with treatment guidelines as accepted by national societies.”

Disclosures: Urovant Sciences provided funding for the study. Roger R. Dmochowski, MD, MMHC, is a consultant for Urovant Sciences.

References

1. Dmochowski RR, Thai S, Iglay K, et al. Increased risk of incident dementia following use of anticholinergic agents: A systematic literature review and meta‐analysis. Neurourol Urodyn. Published online October 23, 2020. doi:10.1002/nau.24536

2. Coupland CA, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;179(8):1084-1093. doi:10.1001/jamainternmed.2019.0677

3. Richardson K, Fox C, Maidment I, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315. doi:10.1136/bmj.k1315