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 volu nteers and to compare these effects with those attributable to diphenh ydramine, another commonly used medication with anticholinergic (musca rinic-blocking) activity. DESIGN: A double-blind, placebo-controlled c ross-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 b y 1 week. MEASUREMENTS: Evaluation of cognitive performance with a 1-h our battery of pencil and paper, interviewer-administered, and compute r-administered tests beginning 90 minutes after drug (or placebo) admi nistration. RESULTS: Random regression analyses demonstrated that oxyb utynin caused significant cognitive decrements on seven of 15 cognitiv e measures, and diphenhydramine caused decrements on five measures. Th e most sensitive measures for detecting the effects of oxybutynin hydr ochloride were the Buschke Selective Reminding Test and Reaction Time. CONCLUSIONS: These findings demonstrate that oxybutynin can cause cog nitive impairment and suggest that physicians prescribing it should mo nitor their patients to facilitate the early recognition of those who experience drug-related cognitive deficits. More generally, the findin gs demonstrate that systematic research with normal volunteers can ide ntify cognitive toxicity not recognized during the process of drug dev elopment or postmarketing surveillance.