Identification of medications that cause cognitive impairment in older people: The case of oxybutynin chloride

OBJECTIVES: To evaluate the cognitive effects of acute challenges with the antispasmodic agent oxybutynin hydrochloride in normal older volunteers and to compare these effects with those attributable to diphenhydramine, another commonly used medication with anticholinergic (muscarinic-blocking) activity. DESIGN: A double-blind, placebo-controlled cross-over study. SETTING: Laboratory evaluations of community subjects. PARTICIPANTS: A convenience sample of 12 volunteers, average age 69.17 years. INTERVENTION: Baseline assessment was followed by randomized administration of a placebo, oxybutynin hydrochloride (5 and 10 mg), and diphenhydramine hydrochloride (50 mg) in test sessions separated by 1 week. MEASUREMENTS: Evaluation of cognitive performance with a 1-hour battery of pencil and paper, interviewer-administered, and computer-administered tests beginning 90 minutes after drug (or placebo) administration. RESULTS: Random regression analyses demonstrated that oxybutynin caused significant cognitive decrements on seven of 15 cognitive measures, and diphenhydramine caused decrements on five measures. The most sensitive measures for detecting the effects of oxybutynin hydrochloride were the Buschke Selective Reminding Test and Reaction Time. CONCLUSIONS: These findings demonstrate that oxybutynin can cause cognitive impairment and suggest that physicians prescribing it should monitor their patients to facilitate the early recognition of those who experience drug-related cognitive deficits. More generally, the findings demonstrate that systematic research with normal volunteers can identify cognitive toxicity not recognized during the process of drug development or postmarketing surveillance.