Paditz Ekkehart, Renner Bertold, Koch Rainer, Schneider Barbara M, Schlarb Angelika A, Ipsiroglu Osman S
Centre for Applied Prevention/Zentrum für Angewandte Prävention, 01307 Dresden, Germany.
Institute of Clinical Pharmacology, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, 01069 Dresden, Germany.
Children (Basel). 2025 May 16;12(5):648. doi: 10.3390/children12050648.
To date, it remains unclear which oral doses and preparation forms of melatonin should be recommended for children and adolescents with non-organic sleep disorders and autism spectrum disorder (ASD). We reviewed the current state of knowledge on this topic based on randomised placebo-controlled trials (RCTs) and diagnosis-related blood melatonin concentrations available in this age group. Two investigators independently searched PubMed, PsycINFO, MEDLINE, and Cochrane CENTRAL on 1 March 2025 for the keywords "melatonin", "autism", and "randomised" in titles and abstracts in all languages, including an evaluation of the references of the reviews, systematic reviews, and meta-analyses published up to that date, some of which were based on searches in numerous databases. Based on this, additional in-depth searches were carried out in PubMed for pharmacokinetic, physiological, and pathophysiological data on melatonin in children and adolescents, with a special focus on ASD. : To date, five RCTs on non-organic sleep disorders in children and adolescents with the sole diagnosis of ASD or with subgroup analyses in the presence of several initial diagnoses such as ADHD, epilepsy, Smith-Magenis, or Fragile X syndrome are available. In these studies, rapid-release, non-delayed preparations were administered orally. In one of these studies, the clinical efficacy of a combination preparation with a sustained-release and a non-released active substance component was tested. Pharmacokinetic data with multiple determinations of melatonin concentrations in the blood are only available for children with ASD in the form of a case series (N = 9). : RCTs comparing the efficacy of delayed melatonin preparations with non-delayed rapid-release oral preparations are not yet available. Physiological data and clinical effects documented in five RCTs indicate that non-delayed melatonin preparations with an initial rapid onset of action are effective for non-organic sleep disorders in children and adolescents with ASD. : From a clinical, pharmacokinetic, and physiological point of view, the RCTs available to date and the data on melatonin concentrations in the blood of children with ASD, measured several times over 24 h, suggest that a low oral melatonin dose and a non-delayed preparation with rapid onset should be started in children and adolescents with non-organic sleep disorders in ASD, if sleep hygiene advice and psychotherapeutic interventions have not demonstrated sufficient effects.
迄今为止，对于患有非器质性睡眠障碍和自闭症谱系障碍（ASD）的儿童和青少年，尚不清楚应推荐何种口服剂量和剂型的褪黑素。我们基于随机安慰剂对照试验（RCT）以及该年龄组中与诊断相关的血液褪黑素浓度，回顾了该主题的当前知识状况。2025年3月1日，两名研究人员独立检索了PubMed、PsycINFO、MEDLINE和Cochrane CENTRAL，查找所有语言标题和摘要中包含“褪黑素”“自闭症”和“随机”的关键词，包括对截至该日期发表的综述、系统评价和荟萃分析的参考文献进行评估，其中一些基于在众多数据库中的检索。在此基础上，又在PubMed中针对儿童和青少年褪黑素的药代动力学、生理学和病理生理学数据进行了深入检索，特别关注ASD。：迄今为止，有五项关于仅诊断为ASD或在存在多动症、癫痫、史密斯-马吉尼斯或脆性X综合征等多种初始诊断情况下进行亚组分析的儿童和青少年非器质性睡眠障碍的RCT。在这些研究中，口服了速释、非缓释制剂。在其中一项研究中，测试了一种含有缓释和非缓释活性物质成分的复方制剂的临床疗效。以病例系列（N = 9）的形式仅获得了ASD儿童多次测定血液中褪黑素浓度的药代动力学数据。：尚无比较缓释褪黑素制剂与非缓释速释口服制剂疗效的RCT。五项RCT中记录的生理学数据和临床效果表明，作用起效迅速的非缓释褪黑素制剂对患有ASD的儿童和青少年的非器质性睡眠障碍有效。：从临床、药代动力学和生理学角度来看，迄今为止可用的RCT以及对ASD儿童24小时内多次测量的血液中褪黑素浓度数据表明，如果睡眠卫生建议和心理治疗干预效果不充分，对于患有ASD非器质性睡眠障碍的儿童和青少年，应开始使用低口服剂量且起效迅速的非缓释制剂。
