Brotizolam: studies of effects on sleep and on performance in young adulthood and in middle age.

Effects of brotizolam (0.2, 0.4 and 0.6 mg), on sleep and performance, were studied in young adults. All doses increased total sleep time, improved the sleep efficiency index, and reduced drowsy sleep and number of awakenings. Brotizolam (0.4 and 0.6 mg) also reduced awake activity. There was some evidence of a delay to the first REM period, but only 0.6 mg reduced the total duration of REM sleep. There were no changes in slow wave sleep. Visuomotor coordination was impaired up to 15.0 h after overnight ingestion of 0.6 mg, but there were no residual effects after the overnight ingestion of 0.2 mg, and with 0.4 mg residual effects did not persist beyond 9.5 h. In middle-aged subjects 0.25 and 0.5 mg were studied. The lower dose (0.25 mg) increased total sleep time, and improved the sleep efficiency index, shortened sleep onset latency, and reduced drowsy sleep. The effect of the higher dose (0.5 mg) was more marked. In a performance study using digit symbol substitution, no residual effect was observed after 0.25 mg brotizolam. Brotizolam is a short-acting hypnotic. Doses up to 0.25 mg are likely to prove adequate over the main span of life and be free of adverse effects on sleep and residual effects on performance.