Objective

A recent 3-month double-blind, placebo-controlled study demonstrated efficacy and safety of pediatric prolonged-release melatonin (PedPRM) for insomnia in children with autism spectrum disorder. This study examined the long-term effects of PedPRM treatment on sleep, growth, body mass index, and pubertal development.

Method

Eighty children and adolescents (2–17.5 years of age; 96% with autism spectrum disorder) who completed the double-blind, placebo-controlled trial were given 2 mg, 5 mg, or 10 mg PedPRM nightly up to 104 weeks, followed by a 2-week placebo period to assess withdrawal effects.

Results

Improvements in child sleep disturbance and caregiver satisfaction with child sleep patterns, quality of sleep, and quality of life were maintained throughout the 104-week treatment period (p < .001 versus baseline for all). During the 2-week withdrawal placebo period, measures declined compared with the treatment period but were still improved compared with baseline. PedPRM was generally safe; the most frequent treatment-related adverse events were fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%). Changes in mean weight, height, body mass index, and pubertal status (Tanner staging done by a physician) were within normal ranges for age with no evidence of delay in body mass index or pubertal development.

Conclusion

Nightly PedPRM at optimal dose (2, 5, or 10 mg nightly) is safe and effective for long-term treatment in children and adolescents with autism spectrum disorder and insomnia. There were no observed detrimental effects on children’s growth and pubertal development and no withdrawal or safety issues related to the use or discontinuation of the drug.

Clinical trial registration information

Efficacy and Safety of Circadin in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities; https://clinicaltrials.gov/; NCT01906866.

中文翻译：

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孤独症谱系障碍儿童长期释放褪黑激素2年后的睡眠，生长和青春期

目的

最近的一项为期3个月的双盲，安慰剂对照研究表明，小儿缓释褪黑激素（PedPRM）对自闭症谱系障碍儿童失眠的疗效和安全性。这项研究检查了PedPRM治疗对睡眠，生长，体重指数和青春期发育的长期影响。

方法

完成双盲，安慰剂对照试验的80名儿童和青少年（2-17.5岁；自闭症谱系障碍的96％）每晚接受104 mg / d的PedPRM 2 mg，5 mg或10 mg每晚治疗，随后进行为期两周的安慰剂期，以评估戒断效果。

结果

在整个104周的治疗期内，儿童睡眠障碍的改善以及护理人员对儿童睡眠模式，睡眠质量和生活质量的满意度得到了改善（ 与所有基线相比，p <.001）。在为期两周的戒断安慰剂期间，与治疗期相比，测量值有所下降，但与基线相比仍有所改善。PedPRM通常是安全的；与治疗相关的最常见不良事件是疲劳（6.3％），嗜睡（6.3％）和情绪波动（4.2％）。平均体重，身高，体重指数和青春期状态的变化（由医生进行的坦纳分期）在正常年龄范围内，没有证据表明体重指数或青春期发育延迟。

结论

每晚最佳剂量的PedPRM（每晚2、5或10 mg）对于自闭症谱系障碍和失眠的儿童和青少年长期治疗是安全有效的。没有观察到对儿童生长和青春期发育的有害影响，也没有与使用或停药有关的戒断或安全问题。

临床试验注册信息

Circadin治疗神经发育障碍儿童睡眠障碍的功效和安全性；https://clinicaltrials.gov/; NCT01906866。