Examination of the cognitive effects of cimetidine in normal elderly volunteers.

The authors evaluated the cognitive effects of acute challenges with the H2 receptor-antagonist cimetidine in normal older volunteers. The study was a double-blind, placebo-controlled, crossover study of 12 volunteers, average age 71.25 years. Baseline assessment was followed by randomized administration of a placebo or ascending doses of cimetidine (400 mg, 800 mg, or 1,600 mg) in test sessions separated by 1 week. Cognitive performance was evaluated with a 1-hour battery of tests beginning 90 minutes after administration of a single dose of drug (or placebo). There were no significant cognitive decrements associated with cimetidine. Despite numerous case reports of cognitive toxicity, this study found no observable decrements in cognitive performance in a group of healthy elderly subjects; therefore, case reports in the literature may be reporting effects for patients with specific impairments or sensitivities.

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.

Identification of drug-related cognitive impairment in older individuals. Challenge studies with diphenhydramine.

The authors tested the use of repeated cognitive measures to identify those older individuals who experience cognitive decline after administration of a centrally acting medication. Subjects were 30 medically stable, older volunteers, mean age 71.4. Administration was a double-blind, placebo-controlled, crossover "challenge" from baseline to placebo, 50 mg, or 75 mg of diphenhydramine. More patients exhibited significant cognitive decrements after 75 mg of diphenhydramine than after placebo on the Buschke Selective Reminding Test Total Recall and the Trails B test. Data were consistent with models based on prediction intervals. Quantitative algorithms using prediction equations can characterize the normal limits of within-subject variability and define excessive cognitive change in elderly subjects, showing promise for use in monitoring patients to identify those who experience mild cognitive toxicity from prescribed medications.