Study of nocturnal sleep and the carryover effects of triazolam and brotizolam using neurophysiological and subjective methods.
In the present study, the effects of short-acting benzodiazepines on nocturnal sleep and the carryover effects of these drugs were studied. The study involved 10 young, healthy male subjects who had given their written informed consent to participate. Either a placebo (PLA), 0.125 mg triazolam (TRZ), 0.25 mg TRZ or 0.25 mg brotizolam (BRZ) was administered to the subjects in a double-blind crossover design by randomized allocation with a single oral administration at 23.00 h. A polysomnography (PSG) was recorded for each subject from 23.00 to 07.00 h the following day. Then, the Stanford Sleepiness Scale (SSS) and Kwansei Gakuin Sleepiness Scale (KSS) were checked between 07.55 and 08.00 h, and the sleep latency test (SLT) was performed between 08.00 and 08.20 h. Event-related potentials (ERPs) were then recorded with an oddball paradigm; the reaction time (RT) was measured simultaneously. According to the PSG, treatment with 0.25 mg TRZ resulted in a statistically significant increase in the percentage of stage 2 sleep (p < 0.05) and a reduction in the percentage of rapid eye movement sleep (p < 0.05) compared with PLA. None of the drugs had any effect on the percentage of slow-wave sleep compared with PLA. With regard to carryover effects, although none of the drugs had any effect on SSS, KSS, RT or ERPs, BRZ did cause a statistically significant decrease in sleep latency (p < 0.05) compared with PLA. TRZ (0.125 and 0.25 mg) and 0.25 mg BRZ exerted different effects on SLT. We suggest that these different effects are attributable to differences in the half-life of these hypnotics.
Suzuki
Hideaki
H
Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan. h-suzuki@nms.ac.jp
Yamadera
Hiroshi
H
Asayama
Kentaro
K
Kudo
Yoshihisa
Y
Ito
Takao
T
Tamura
Yoshiatsu
Y
Endo
Shunkichi
S
D000328:Adult; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000502:physiology*; D018592:Cross-Over Studies; D006970:Disorders of Excessive Somnolence / Q000175:diagnosis; D004311:Double-Blind Method; D005071:Evoked Potentials / Q000502:physiology; D005133:Eye Movements / Q000187:drug effects; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017286:Polysomnography; D011930:Reaction Time / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D011795:Surveys and Questionnaires; D014229:Triazolam / Q000008:administration & dosage / Q000494:pharmacology*
D001381:Azepines; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D014229:Triazolam; C020960:brotizolam