Age-related increase in CNS sensitivity to benzodiazepines as assessed by task difficulty.

The differential sensitivity of young and elderly healthy adults to the impairment effects of benzodiazepines was assessed by tasks with several levels of difficulty. Using a double-blind procedure, single doses of placebo, alprazolam (0.75 and 1.5 mg) and triazolam (0.25 and 0.5 mg) were ingested orally by 10 young men, 9 young women, 7 elderly men, and 10 elderly women. Order of drug administration was determined by a random Latin square design. Different versions of the subcritical tracking and digit symbol substitution tasks were characterized by three difficulty levels. Assessments of task performance were conducted at varying intervals for 7 h after drug administration. Both drugs induced a rapid initial onset of impairment in the two age groups. Evidence of increased drug sensitivity in the elderly was provided by the more prolonged duration of the pharmacologic effect in the older than young subjects, especially for the harder versions of the SCT and DSS tasks. In summary, the data provide support for the hypothesis of an age-related decline in the adaptive capacity to inhibit adverse drug effects.