Experimental and Clinical Pharmacology Department, CHU Rennes, 35033 Rennes, France.
Inserm, CIC 1414 (Clinical Investigation Center), 35033 Rennes, France.
Int J Mol Sci. 2021 Feb 2;22(3):1490. doi: 10.3390/ijms22031490.
The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin's effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.
褪黑素在病理生理条件下的作用已被广泛研究，包括自闭症谱系障碍（ASD）。ASD 中褪黑素分泌减少，导致许多临床试验使用即时释放和延长释放的口服褪黑素制剂。然而，褪黑素在 ASD 中的作用和剂型选择需要进一步研究。褪黑素对 ASD 睡眠障碍的治疗益处已被观察到，特别是在睡眠潜伏期和睡眠质量方面。重要的是，褪黑素在改善自闭症行为障碍方面也可能发挥作用。本文的目的是综述影响褪黑素治疗反应的因素和褪黑素给药后的可能副作用。似乎暴露于外源性褪黑素的影响取决于年龄、性别、给药途径和时间、剂型类型、剂量以及与几种物质（如烟草或避孕药）的相互作用。此外，在典型发育和 ASD 中未描述与褪黑素相关的主要不良反应。总之，褪黑素目前是 ASD 儿童和青少年睡眠障碍的一种经过充分验证和耐受的治疗方法。更全面地考虑影响褪黑素药代动力学的因素可以阐明褪黑素在该人群中的最佳应用。需要在 ASD 中进行进一步的研究，以探索褪黑素对睡眠问题和自闭症行为障碍的剂量-效应关系。
