King's College London and Evelina Children's Hospital, St Thomas' Hospital, London SE1 7EH, UK.
BMJ. 2012 Nov 5;345:e6664. doi: 10.1136/bmj.e6664.
To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders.
12 week double masked randomised placebo controlled phase III trial.
19 hospitals across England and Wales.
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.
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.
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.
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.
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.
ISRCT No 05534585.
评估褪黑素治疗神经发育障碍儿童严重睡眠问题的疗效和安全性。
12 周双盲随机安慰剂对照 III 期试验。
英格兰和威尔士的 19 家医院。
146 名 3 岁至 15 岁 8 个月大的儿童被随机分组。他们患有一系列神经发育障碍，并且在随机分组前 4 至 6 周接受了父母的标准睡眠行为建议手册后，睡眠问题仍未得到改善。睡眠问题的定义是入睡时间超过熄灯后 1 小时，或连续睡眠时间少于 6 小时。
立即释放褪黑素或匹配的安慰剂胶囊，在儿童睡前 45 分钟服用，持续 12 周。所有儿童开始服用 0.5 毫克胶囊，根据治疗反应增加至 2 毫克、6 毫克和 12 毫克。
根据父母完成的睡眠日记中记录的基线，调整后 12 周的夜间总睡眠时间。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。睡眠通过日记和活动记录仪进行测量。
褪黑素通过睡眠日记（n=110）增加了 22.4 分钟（95%置信区间 0.5 至 44.3 分钟）的总睡眠时间，通过活动记录仪（n=59）增加了 13.3 分钟（-15.5 至 42.2 分钟）。褪黑素还缩短了入睡潜伏期，睡眠日记（-37.5 分钟，-55.3 至-19.7 分钟）和活动记录仪（-45.3 分钟，-68.8 至-21.9 分钟），对于潜伏期最长的儿童最为有效（P=0.009）。褪黑素与安慰剂相比，起床时间更早（29.9 分钟，13.6 至 46.3 分钟）。儿童行为和家庭功能结果显示有所改善，且倾向于使用褪黑素。不良事件轻微，两组相似。
儿童在服用褪黑素后睡眠并没有明显增加；尽管入睡时间明显加快，但起床时间更早。儿童行为和家庭功能结果没有显著改善。在这三个月期间，褪黑素是可耐受的。需要与慢释放褪黑素制剂或褪黑素类似物进行比较。
ISRCTN52026465。
