Dose-related effects of flurazepam on human sleep-waking patterns

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Abstract
Two consecutive nights of flurazepam at each of 15, 26, and 45 mg were compared to placebo in a Latin-square double-blind crossover design using 24 healthy young-adult males. Flurazepam had significant hypnotic effects on objective and subjective measures of efficacy: shorter sleep latency, longer sleep time, and fewer awakenings. It also induced morning sedation along with decrements in cognitive performance. Flurazepam had dose-related impacts on both human and computer-scored EEG-EOG parameters: less stages 3+4 and decreased EEG δ, less stage 1 REM and decreased REM density, more stage 2 and increased EEG spindling. Also, EEG α and movement artifact were decreased and EEG β was increased. Only a few of the EEG-EOG variables and none of the subjective indices had cumulative changes on the two drug nights. Stage shifting was unaffected at the two lower doses on the first night but decreased at all three dose levels on the second night; percent stages 3+4 was unaffected on the first night but decreased at all dose levels on the second night. The rate of δ waveform activity was also diminished by a greater amount on the second night. This study conclusively established that flurazepam affects the EEG-EOG architecture of sleep on each of the first two nights of administration.