Garfinkel D, Laudon M, Nof D, Zisapel N
Day Care Unit, E Wolfson Medical Center, Holon, Israel.
Lancet. 1995 Aug 26;346(8974):541-4. doi: 10.1016/s0140-6736(95)91382-3.
Melatonin, produced by the pineal gland at night, has a role in regulation of the sleep-wake cycle. Among elderly people, even those who are healthy, the frequency of sleep disorders is high and there is an association with impairment of melatonin production. We investigated the effect of a controlled-release formulation of melatonin on sleep quality in 12 elderly subjects (aged 76 [SD 8] years) who were receiving various medications for chronic illnesses and who complained of insomnia. In all 12 subjects the peak excretion of the main melatonin metabolite 6-sulphatoxymelatonin during the night was lower than normal and/or delayed in comparison with non-insomniac elderly people. In a randomised, double-blind, crossover study the subjects were treated for 3 weeks with 2 mg per night of controlled-release melatonin and for 3 weeks with placebo, with a week's washout period. Sleep quality was objectively monitored by wrist actigraphy. Sleep efficiency was significantly greater after melatonin than after placebo (83 [SE 4] vs 75 [3]%, p < 0.001) and wake time after sleep onset was significantly shorter (49 [14] vs 73 [13] min, p < 0.001). Sleep latency decreased, but not significantly (19 [5] vs 33 [7] min, p = 0.088). Total sleep time was not affected. The only adverse effects reported were two cases of pruritus, one during melatonin and one during placebo treatment; both resolved spontaneously. Melatonin deficiency may have an important role in the high frequency of insomnia among elderly people. Controlled-release melatonin replacement therapy effectively improves sleep quality in this population.
褪黑素由松果体在夜间分泌，对睡眠 - 清醒周期的调节起作用。在老年人中，即使是健康的老年人，睡眠障碍的发生率也很高，且与褪黑素分泌受损有关。我们调查了褪黑素控释制剂对12名老年受试者（年龄76[标准差8]岁）睡眠质量的影响，这些受试者因慢性疾病正在接受各种药物治疗且主诉失眠。与非失眠的老年人相比，所有12名受试者夜间主要褪黑素代谢物6 - 硫酸氧褪黑素的峰值排泄均低于正常水平和/或延迟。在一项随机、双盲、交叉研究中，受试者每晚服用2毫克褪黑素控释制剂治疗3周，服用安慰剂治疗3周，中间有一周的洗脱期。通过手腕活动记录仪客观监测睡眠质量。服用褪黑素后的睡眠效率显著高于服用安慰剂后（83[标准误4]%对75[3]%，p<0.001），睡眠开始后的清醒时间显著缩短（49[14]分钟对73[13]分钟，p<0.001）。睡眠潜伏期缩短，但不显著（19[5]分钟对33[7]分钟，p = 0.088）。总睡眠时间未受影响。报告的唯一不良反应是两例瘙痒，一例在褪黑素治疗期间，一例在安慰剂治疗期间；均自行缓解。褪黑素缺乏可能在老年人失眠的高发生率中起重要作用。褪黑素控释替代疗法可有效改善该人群的睡眠质量。
