一项关于褪黑素治疗阿尔茨海默病睡眠障碍的多中心、安慰剂对照试验。
A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease.
作者信息
Singer Clifford, Tractenberg Rochelle E, Kaye Jeffrey, Schafer Kim, Gamst Anthony, Grundman Michael, Thomas Ronald, Thal Leon J
机构信息
Department of Psychiatry, Oregon Health & Science University, Portland, USA.
出版信息
Sleep. 2003 Nov 1;26(7):893-901. doi: 10.1093/sleep/26.7.893.
OBJECTIVES
To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer's disease.
DESIGN
A multicenter, randomized, placebo-controlled clinical trial of 2 dose formulations of oral melatonin coordinated by the National Institute of Aging-funded Alzheimer's Disease Cooperative Study. Subjects with Alzheimer's disease and nighttime sleep disturbance were randomly assigned to 1 of 3 treatment groups: placebo, 2.5-mg slow-release melatonin, or 10-mg melatonin.
SETTING
Private homes and long-term care facilities.
PARTICIPANTS
157 individuals were recruited by 36 Alzheimer's disease research centers. Subjects with a diagnosis of Alzheimer's disease were eligible if they averaged less than 7 hours of sleep per night (as documented by wrist actigraphy) and had 2 or more episodes per week of nighttime awakenings reported by the caregiver.
MEASUREMENTS
Nocturnal total sleep time, sleep efficiency, wake-time after sleep onset, and day-night sleep ratio during 2- to 3-week baseline and 2-month treatment periods. Sleep was defined by an automated algorithmic analysis of wrist actigraph data.
RESULTS
No statistically significant differences in objective sleep measures were seen between baseline and treatment periods for the any of the 3 groups. Nonsignificant trends for increased nocturnal total sleep time and decreased wake after sleep onset were observed in the melatonin groups relative to placebo. Trends for a greater percentage of subjects having more than a 30-minute increase in nocturnal total sleep time in the 10-mg melatonin group and for a decline in the day-night sleep ratio in the 2.5-mg sustained-release melatonin group, compared to placebo, were also seen. On subjective measures, caregiver ratings of sleep quality showed improvement in the 2.5-mg sustained-release melatonin group relative to placebo. There were no significant differences in the number or seriousness of adverse events between the placebo and melatonin groups.
CONCLUSIONS
Based on actigraphy as an objective measure of sleep time, melatonin is not an effective soporific agent in people with Alzheimer's disease.
目的
确定两种剂量配方的褪黑素治疗阿尔茨海默病患者失眠的安全性和有效性。
设计
一项由美国国立衰老研究所资助的阿尔茨海默病协作研究协调进行的多中心、随机、安慰剂对照临床试验，涉及两种剂量配方的口服褪黑素。患有阿尔茨海默病且夜间睡眠障碍的受试者被随机分配到3个治疗组之一：安慰剂组、2.5毫克缓释褪黑素组或10毫克褪黑素组。
地点
私人住宅和长期护理机构。
参与者
36个阿尔茨海默病研究中心招募了157名个体。诊断为阿尔茨海默病的受试者若平均每晚睡眠少于7小时（通过手腕活动记录仪记录）且护理人员报告每周有2次或更多次夜间觉醒，则符合条件。
测量指标
在2至3周的基线期和2个月的治疗期内，夜间总睡眠时间、睡眠效率、睡眠开始后的清醒时间以及昼夜睡眠比。睡眠通过对手腕活动记录仪数据进行自动算法分析来定义。
结果
3组中任何一组在基线期和治疗期之间的客观睡眠指标均无统计学显著差异。与安慰剂组相比，褪黑素组夜间总睡眠时间增加和睡眠开始后清醒时间减少的趋势不显著。与安慰剂组相比，还观察到10毫克褪黑素组中有更高百分比的受试者夜间总睡眠时间增加超过30分钟，以及2.5毫克缓释褪黑素组昼夜睡眠比下降的趋势。在主观指标方面，护理人员对睡眠质量的评分显示，2.5毫克缓释褪黑素组相对于安慰剂组有所改善。安慰剂组和褪黑素组之间不良事件的数量或严重程度没有显著差异。
结论
基于活动记录仪作为睡眠时间的客观测量方法，褪黑素对阿尔茨海默病患者不是一种有效的催眠剂。
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