Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial
Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial
复制标题
DOI：
10.1136/bmj.e6664
复制
发表时间：
2012-11-05
影响因子：
--
通讯作者：
Appleton, R.
中科院分区：
文献类型：
--
作者：
Gringras, P.;Gamble, C.;Appleton, R.
目的 评估褪黑激素治疗神经发育障碍儿童严重睡眠问题的有效性和安全性。设计 12 周双盲随机安慰剂对照 III 期试验。在英格兰和威尔士的 19 家医院进行。参与者 146 名年龄在 3 岁至 15 岁 8 个月的儿童被随机分组。他们患有一系列神经和发育障碍以及严重的睡眠问题，而随机分组前四到六周向父母提供的标准化睡眠行为建议手册对这些问题没有反应。睡眠问题的定义是孩子在熄灯后一小时内没有入睡或连续睡眠少于六小时。 干预措施 在孩子就寝前 45 分钟立即释放褪黑激素或匹配的安慰剂胶囊，为期 12 周。所有儿童开始时服用 0.5 毫克胶囊，根据他们对治疗的反应，逐渐增加 2 毫克、6 毫克和 12 毫克。 主要结果指标 12 周后夜间总睡眠时间根据家长完成的睡眠日记中记录的基线进行调整。次要结局包括入睡潜伏期、儿童行为评估、家庭功能和不良事件。通过日记和体动记录仪测量睡眠。结果 通过睡眠日记 (n=110) 测量，褪黑素使总睡眠时间增加 22.4 分钟（95% 置信区间 0.5 至 44.3 分钟），通过体动记录仪 (n=59) 测量，使总睡眠时间增加 13.3 分钟（-15.5 至 42.2）。通过睡眠日记（-37.5 分钟、-55.3 至 -19.7 分钟）和体动记录仪（-45.3 分钟、-68.8 至 -21.9 分钟）测量，褪黑激素缩短了入睡潜伏期，并且对于睡眠潜伏期最长的儿童最有效（P=0.009）。与安慰剂相比，褪黑素与更早的醒来时间有关（29.9 分钟、13.6 至 46.3 分钟）。儿童行为和家庭功能结果显示出一些改善并青睐使用褪黑激素。两组之间的不良事件都很轻微且相似。 结论 儿童服用褪黑激素后几乎没有获得额外的睡眠；尽管他们入睡的速度明显加快，但醒来的时间却变得更早。儿童行为和家庭功能结果没有显着改善。在这三个月期间，褪黑激素是可以忍受的。需要与缓释褪黑激素制剂或褪黑激素类似物进行比较。
Objective To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders.Design 12 week double masked randomised placebo controlled phase III trial.Setting 19 hospitals across England and Wales.Participants 146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours' continuous sleep.Interventions Immediate release melatonin or matching placebo capsules administered 45 minutes before the child's bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment.Main outcome measures Total sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy.Results Melatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (-15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (-37.5 minutes, -55.3 to -19.7 minutes) and actigraphy (-45.3 minutes, -68.8 to -21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups.Conclusions Children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required.