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Abstract
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.
Highlights
The analgesic effects of melatonin on chronic pain have been reported in humans and animal models; animal models are of particular interest when studying Central Nervous System (CNS) disorders and the neurobehavioral genetic factors possibly involved in these disorders [8,9]
Whereas endogenous melatonin levels were not affected by smoking, melatonin levels after oral administration were significantly lower (p ≤ 0.02) when smoking than after abstinence, suggesting that CYP1A2 tobacco induction coupled with a supraphysiological level during supplementation can lead to lower melatonin levels
The results suggest that melatonin has therapeutic benefits on several behavioral variables
Summary
The impact of melatonin in central nervous system (CNS) disorders has been the most investigated since its discovery. The analgesic effects of melatonin on chronic pain have been reported in humans and animal models; animal models are of particular interest when studying CNS disorders and the neurobehavioral genetic factors possibly involved in these disorders [8,9]. The main objective of this article is to investigate the impact of PK variability on melatonin bioavailability and its therapeutic and possible side effects in individuals with ASD. In this context, factors influencing exposure to endogenous and exogenous melatonin in healthy individuals are reviewed, as well as melatonin PK properties according to the melatonin administration route and formulation type. The effects of sampling and analytical method strategies on the measurement of melatonin concentrations in healthy and ASD individuals are examined
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