The acute and chronic effects of diazepam on human performance, apart from their theoretical interest, are of considerable practical significance because of the widespread use of this drug. Diazepam effects on performance of elderly individuals are of particular concern, considering the prevailing view that the elderly show increased sensitivity to diazepam effects, and the evidence of age-related increases in diazepam accumulation during multiple dosage. Surprisingly, few studies of benzodiapine effects on task performance have compared effects on elderly and young people. Most such studies, moreover, have involved normal volunteers and have not determined if anxious patients show similar effects. The current study addresses these topics by comparing diazepam effects on performance of normal young, normal elderly, anxious young, and anxious elderly individuals. Using a battery of tasks sensitive to benzodiazepine-induced impairments, effects of administering low and high single diazepam doses will be tested before and after corresponding low-dose or high-dose chronic diazepam regimens. Diazepam and desmethyldiazepam plasma concentrations will be measured in conjunction with all performance tests. This study will provide a clearer answer than is now available to the basic questions: Do young vs. elderly individuals, and anxious vs. normal individuals, differ in the effects of acute and chronic diazepam administration on task performance, and in the development of tolerance to these effects? Additionally, it will determine how acute and chronic diazepam effects and tolerance development vary as a function of diazepam dose, type of task assessment, and time of assessment relative to drug administration; and will determine the relations of diazepam-induced task impairments to diazepam and desmethyldiazepam plasma concentrations, and the influence of age and anxiety on these relations.

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National Institute of Mental Health (NIMH)
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Nathan Kline Institute for Psychiatric Research
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