Differential Effects of the Antimuscarinic Agents Darifenacin and Oxybutynin ER on Memory in Older Subjects

• Published in: European urology Vol. 50; no. 2; pp. 317 - 326
• Main Authors: Kay, Gary, Crook, Thomas, Rekeda, Ludmyla, Lima, Raul, Ebinger, Ursula, Arguinzoniz, Miguel, Steel, Michael
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.08.2006; Elsevier
• Subjects: Aged; Analysis of Variance; Antimuscarinic; Attention; Benzofurans - adverse effects; Biological and medical sciences; Cognitive function; Darifenacin; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mandelic Acids - adverse effects; Medical sciences; Memory Disorders - chemically induced; Memory Disorders - diagnosis; Middle Aged; Muscarinic Antagonists - adverse effects; Nephrology. Urinary tract diseases; Neuropsychological Tests; Older subjects; Oxybutynin ER; Psychomotor Performance; Pyrrolidines - adverse effects; Reaction Time; Urinary Bladder, Overactive - drug therapy; Oxybutynin ER; Antimuscarinic; Darifenacin; Older subjects; Cognitive function; M3 Muscarinic receptor; Human; Nephrology; Memory; Cognition; Urology; Cholinergic receptor; Antispasmodic agent; Muscarinic receptor; Oxybutynin; Antagonist; Parasympatholytic; Age
• DOI: 10.1016/j.eururo.2006.03.057
• ISSN: 0302-2838

To investigate the effects of darifenacin controlled-release (CR) and oxybutynin extended-release (ER) on cognitive function (particularly memory) in older subjects. Healthy subjects (n=150) ≥60 years were randomised to darifenacin, oxybutynin ER or placebo in a multicentre, double-blind, double-dummy, parallel-group, 3-week study. Doses were administered according to US labels: oxybutynin ER 10mg once daily (od), increasing to 15mg od then 20mg od by week 3; darifenacin 7.5mg od in weeks 1 and 2, then 15mg od in week 3. The primary end point was accuracy on the Name–Face Association Test (delayed recall) at week 3. Results of the Name–Face Association Test at week 3 showed no significant difference between darifenacin and placebo on delayed recall (mean difference, −0.06, p=0.908). In contrast, oxybutynin ER resulted in memory impairment, with significantly lower scores than placebo and darifenacin (mean differences, −1.30, p=0.011 and −1.24, p=0.022, respectively) for delayed recall on the Name–Face Association Test at week 3. Additional tests of delayed recall indicated significant memory impairment with oxybutynin ER versus placebo at certain time points, whereas darifenacin was similar to placebo. No between-treatment differences were detected in self-rated memory, demonstrating that subjects were unaware of memory deterioration. While darifenacin had no significant effects on memory versus placebo, oxybutynin ER caused significant memory deterioration (magnitude of effect comparable to brain aging of 10 years). The results also demonstrate that subjects may not recognise/report memory deterioration.