Background: Although observations have shown that half a tablet (0.125 mg) of brotizolam develops an adequate sedative effect in patients who cannot get to sleep, confirmatory pharmacodynamic studies are lacking.
Method: In a comparative double-blind, randomized, placebo-controlled study, the hypnotic effects of 0.125 mg and 0.250 mg brotizolam, a short-acting benzodiazepine-like hetrazepine, were investigated. The concept underlying the study was that both doses are equally rapid in action onset, but differ in duration of effect. The study included 49 healthy women aged between 23 and 44 years. The nocturnal tests lasted until 2.30 am, and a concluding examination took place after breakfast. The test subjects were asked to estimate their state of well-being on visual analog scales at half-hour intervals, while concentration was tested hourly using the digit symbol substitution test (DSST) tried and tested in numerous studies on benzodiazepines.
Results: Both doses proved to be equally effective after 0.5, 1.5 and 2.5 hours. While the hypnotic effect of the lower dose no longer differed from that of placebo after 3.5 hours, the larger dose still had a greater effect than both placebo and the lower dose after 4.5 hours. A hangover effect in the morning was not observed with either dose. The pharmacodynamic results indicate that the effect of the substance is readily controllable, and that half a tablet of brotizolam is an effective treatment of difficulty in getting to sleep initially or after waking prematurely.
Conclusion: The results of the present study demonstrate for the first time that a half-tablet of brotizolam is an effective treatment of difficulty in getting to sleep initially or after premature wakening.