Hughes R J, Sack R L, Lewy A J
Department of Psychiatry, School of Medicine, Oregon Health Sciences University, Portland, USA.
Sleep. 1998;21(1):52-68.
The present investigation used a placebo-controlled, double-blind, crossover design to assess the sleep-promoting effect of three melatonin replacement delivery strategies in a group of patients with age-related sleep-maintenance insomnia. Subjects alternated between treatment and "washout" conditions in 2-week trials. The specific treatment strategies for a high physiological dose (0.5 mg) of melatonin were: (1) EARLY: An immediate-release dose taken 30 minutes before bedtime; (2) CONTINUOUS: A controlled-release dose taken 30 minutes before bedtime; (3) LATE: An immediate-release dose taken 4 hours after bedtime. The EARLY and LATE treatments yielded significant and unambiguous reductions in core body temperature. All three melatonin treatments shortened latencies to persistent sleep, demonstrating that high physiological doses of melatonin can promote sleep in this population. Despite this effect on sleep latency, however, melatonin was not effective in sustaining sleep. No treatment improved total sleep time, sleep efficiency, or wake after sleep onset. Likewise, melatonin did not improve subjective self-reports of nighttime sleep and daytime alertness. Correlational analyses comparing sleep in the placebo condition with melatonin production revealed that melatonin levels were not correlated with sleep. Furthermore, low melatonin producers were not preferentially responsive to melatonin replacement. Total sleep time and sleep efficiency were correlated with the timing of the endogenous melatonin rhythm, and particularly with the phase-relationship between habitual bedtime and the phase of the circadian timing system.
本研究采用安慰剂对照、双盲、交叉设计，以评估三种褪黑素替代给药策略对一组患有与年龄相关的睡眠维持性失眠患者的促睡眠效果。在为期2周的试验中，受试者在治疗和“洗脱”条件之间交替。高生理剂量（0.5毫克）褪黑素的具体治疗策略为：（1）早期：睡前30分钟服用速释剂量；（2）持续：睡前30分钟服用控释剂量；（3）晚期：睡后4小时服用速释剂量。早期和晚期治疗均使核心体温显著且明确降低。所有三种褪黑素治疗均缩短了进入持续睡眠的潜伏期，表明高生理剂量的褪黑素可促进该人群的睡眠。然而，尽管对睡眠潜伏期有此作用，但褪黑素在维持睡眠方面无效。没有一种治疗方法能改善总睡眠时间、睡眠效率或睡眠开始后的觉醒情况。同样，褪黑素也未改善夜间睡眠和白天警觉性的主观自我报告。将安慰剂条件下的睡眠与褪黑素分泌进行比较的相关分析表明，褪黑素水平与睡眠无关。此外，低褪黑素分泌者对褪黑素替代治疗并无优先反应。总睡眠时间和睡眠效率与内源性褪黑素节律的时间有关，特别是与习惯性就寝时间和昼夜节律系统相位之间的相位关系有关。
