Overactive Bladder Drugs Tied to Increased Dementia Risk in Diabetes

The use of oxybutynin, solifenacin, and tolterodine for overactive bladder (OAB) was tied to an increased risk for dementia in patients with diabetes, according to a paper published in the PLoS One journal.

OAB, characterized by urinary frequency and urgency, is commonly treated with anticholinergics such as oxybutynin, solifenacin, and tolterodine. Anticholinergics not only target bladder smooth muscle muscarinic acetylcholine receptors but also receptors in the brain. Controversy remains regarding the risk of dementia with anticholinergic use, particularly in patients with diabetes who are at a higher risk of dementia.

Yu-Wan Yang, of the department of neurology at China Medical University Hospital in Taichung, Taiwan, and colleagues sought to investigate the risk of dementia in patients with diabetes associated with oxybutynin, solifenacin, and tolterodine use for OAB.

The investigators conducted a cohort study of diabetic patients using data from the Taiwan National Health Insurance Research Database from 2002 through 2013. The study included 10,938 patients who received one of the anticholinergic medications and 564,733 who did not receive any of the medications.

The 6-year event rate for dementia was estimated at 3.9% in the oxybutynin group, 4.3% in the solifenacin group, 2.2% in the tolterodine group, and 1.2% in the control group (P <.001). The dementia event rates decreased in the solifenacin group (4.3% to 3.5%) and the oxybutynin group (3.9% to 3.0%) but increased from 1.2% to 2.4% in the control group. 

Adjusted hazard ratios (HRs) for dementia were 2.30 (95% CI: 1.63-3.23) for oxybutynin use, 2.26 (95% CI: 1.62-3.14) for solifenacin use, and 2.04 (95% CI: 1.41-2.95) for tolterodine use compared with nonuse. Using death as a competing event, the adjusted HR for dementia in patients with diabetes was 2.35 (95% CI: 1.96-2.81) for oxybutynin use, 2.16 (95% CI: 1.81-2.58) for solifenacin use, and 2.24 (95% CI: 1.85-2.73) for tolterodine use compared with nonuse.

The study was limited by unknown severity of OAB symptoms in participants and no comparison with a nondiabetic control group.

“Our research [shows] that long-term use of a particular anticholinergic drug may increase subsequent risk of developing dementia. This is a key finding for clinicians who must keep this potentially increased risk in mind when prescribing long-term use of a specific anticholinergic drug to DM patients suffering from OAB,” the investigators wrote.


Yang Y-W, Liu H-H, Lin T-H, et al. Association between different anticholinergic drugs and subsequent dementia risk in patients with diabetes mellitus. PLoS ONE. 12(4):e0175335. doi:10.1371/journal.pone.0175335