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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.

The hypnotic activity of acute doses of 0.125 mg and 0.250 mg brotizolam (CAS 57801-81-7, Lendormin) was compared in a double-blind randomised placebo-controlled study. Forty-nine healthy female volunteers aged between 23 and 44 years were enrolled. Trial medication was administered sublingually at 9:15 p.m. and 9:30 p.m., respectively. The nocturnal investigations continued until 2:30 a.m. A final examination was performed in the morning after breakfast. Every 30 min mood was measured by visual analogue scales. A computerised psychometric test (CDT) over 8 min was undertaken in order to measure continuous attention under short-term memory load. The Digit Symbol Substitution Test (DSST) was performed every hour. The CDT was not evaluable due to significant baseline differences. A statistically significant sedative effect in the DSST was already found 30 min after administration of 0.250 mg brotizolam, while the effect of 0.125 mg brotizolam just failed to reach the threshold of significance. Both treatments showed equivalent efficacy at 0.5, 1.5 and 2.5 h after administration. After 3.5 and 4.5 h there was no statistically significant difference between placebo and 0.125 mg brotizolam. After 4.5 h 0.250 mg brotizolam still showed significant hypnotic activity compared to placebo and 0.125 mg brotizolam. No treatment effects on mood were apparent according to the visual analogue scales. Furthermore, no hangover effects were detected for any of the parameters measured. The pharmacodynamic results confirmed the duration of action of more than 4.5 of h 0.250 mg brotizolam found in earlier studies and suggest that 0.125 mg is as effective as 0.250 mg with regard to sleep onset disturbances but has a shorter duration of action.