Midazolam: Dose-response studies of effectiveness and rebound insomnia

Midazolam, an investigational hypnotic, was evaluated for effectiveness, side effects, and withdrawal phenomena in doses of 10, 20, and 30 mg in three separate sleep laboratory studies, each including 4 placebo-baseline nights, 7 drug nights, and 3 placebo-withdrawal nights. Only a slight to moderate degree of effectiveness was shown across the three doses; this effectiveness was much more pronounced during the first third of the night. There was no dose-response effect for effectiveness with either initial or continued drug administration. In general, there was less effectiveness on the last 3 drug nights, indicating a potential for the development of tolerance over a relatively short period of time. Following withdrawal there was a marked dose-related worsening of sleep above baseline levels (rebound insomnia).