Tadaaki Nagoya

Residual Effects of Repeated Administration of Triazolam and Nitrazepam in Healthy Volunteers

The residual effects of hypnotics were investigated with a long-acting (nitrazepam) and a short-acting (triazolam) benzodiazepine hypnotic in 8 male volunteers. Subjects received placebo, nitrazepam 5 mg, or triazolam 0.25 mg for 7 consecutive nights in a random-order, double-blind crossover design. Daytime sleepiness, psychomotor performance, EEG activity and standing steadiness were assessed in the morning after 1, 4, and 7 days of drug treatment. Plasma concentrations of nitrazepam and triazolam were also assayed. The concentration of nitrazepam increased gradually during the course of treatment and was associated with residual sedative effects on days 4 and 7. Nitrazepam produced no apparent psychomotor impairments in these studies. On the other hand, there was no evidence of drug accumulation after triazolam administration and triazolam showed no residual sedative effects or residual impairment of psychomotor performance during the experiment. Thus, short-acting hypnotics may have an advantage over long-acting hypnotics in terms of producing less residual sedative effects during chronic treatment.