Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Oct 27:14:1927-1944.
doi: 10.2147/NSS.S340944. eCollection 2022.

Melatonin Treatment for Pediatric Patients with Insomnia: Is There a Place for It?

Julie Rolling #  1   2   3   4 , Juliette Rabot #  1   2   3   5   6 , Carmen M Schroder  1   2   3   4   5   6
Affiliations
Review

Melatonin Treatment for Pediatric Patients with Insomnia: Is There a Place for It?

Julie Rolling et al. Nat Sci Sleep. .

Abstract

Sleep is a vital physiological function that is impaired in ranges from 10% in the typically developing pediatric population to over 80% in populations of children with neurodevelopmental disorders and/or psychiatric comorbidities. Pediatric insomnia disorder is an increasing public health concern given its negative impact on synaptic plasticity involved in learning and memory consolidation but also on mood regulation, hormonal development and growth, and its significant impact on quality of life of the child, the adolescent and the family. While first-line treatment of pediatric insomnia should include parental education on sleep as well as sleep hygiene measures and behavioural treatment approaches, pharmacological interventions may be necessary if these strategies fail. Melatonin treatment has been increasingly used off-label in pediatric insomnia, given its benign safety profile. This article aims to identify the possible role of melatonin treatment for pediatric insomnia, considering its physiological role in sleep regulation and the differential effects of immediate release (IR) versus prolonged release (PR) melatonin. For the physician dealing with pediatric insomnia, it is particularly important to be able to distinguish treatment rationales implying different dosages and times of treatment intake. Finally, we discuss the benefit-risk ratio for melatonin treatment in different pediatric populations, ranging from the general pediatric population to children with different types of neurodevelopmental disorders, such as autism spectrum disorder or ADHD.

Keywords: ADHD; autism spectrum disorder; circadian; delayed sleep phase syndrome; immediate release; melatonin; pediatric insomnia; prolonged release; sleep.

PubMed Disclaimer

Conflict of interest statement

Prof. Dr. Carmen M Schroder reports grants and/or personal fees from Neurim and Biocodex, outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Melatonin, an endogenous synchronizer of the circadian system. Adapted from Claustrat B. Mélatonine et troubles du rythme veille-sommeil. Médecine Sommeil. 2009;6(1):12–24. Copyright©2009. Elsevier Masson SAS. All rights reserved. and Schröder CM, Broquère MA, Claustrat B, et al. Approches thérapeutiques des troubles du sommeil et des rythmes chez l’enfant avec TSA. L’Encéphale. 2022:S0013700621002177.Open Access.
Figure 2
Figure 2
The chronobiotic action of melatonin: modification of endogenous melatonin secretion after administration of immediate release melatonin according to the phase response curve. Depending on the time of administration of immediate release melatonin, the central clock responds with a phase advance or delay. The melatonin rhythm constitutes a faithful marker of the activity of the clock allowing to objectify the phenomenon. (A) Control. (B) The plasma profile shows a phase advance after administration in the afternoon or evening, and (C), a phase delay after administration in the morning. The critical time (or turning point) which corresponds to the change in the direction of the phase change is around 15:00. Adapted from Claustrat B. Mélatonine: aspects biochimiques, physiologiques et pharmacologiques en relation avec les phénomènes rythmiques et le sommeil. Médecine Sommeil. 2020;17(3):177–194 and Claustrat B. Mélatonine et troubles du rythme veille-sommeil. Médecine Sommeil. 2009;6(1):12–24. Elsevier Masson SAS. All rights reserved.,
Figure 3
Figure 3
Effect of immediate release melatonin on distal vasodilatation. Illustration of the analysis of the topographic temperature with infrared thermometry in an individual (dorsal and palmar side of the hand) 1 h after taking a placebo and 1 h after taking 5 mg of immediate release melatonin (oral intake), the latter indicating a greater increase in skin blood flow by melatonin in the fingertip than in the proximal finger, most likely by opening arteriovenous anastomoses. Immediate release melatonin administration during the day (absence of endogenous melatonin secretion) mimics the endogenous thermophysiological processes that occur in the evening and induces sleepiness. Adapted from Kräuchi K, Cajochen C, Pache M, Flammer J, Wirz‐Justice A. Thermoregulatory effects of melatonin in relation to sleepiness. Chronobiol Int. 2006;23(1–2):475–484, Taylor & Francis Ltd, http://www.tandfonline.com by permission of the publisher.
Figure 4
Figure 4
Comparison of plasma pharmacokinetics after administration of immediate release and prolonged release melatonin preparations. Plasma kinetics after administration of administration of immediate release melatonin (2 mg dose, light grey curve) versus prolonged release melatonin (2 mg dose, dark curve). Adapted from Zisapel N. Melatonin and sleep. Open Neuroendocrinol J. 2010;3:85–95.
Figure 5
Figure 5
Chronotype variation across lifetime, depending on gender. Chronotype was assessed through the Munich Chronotype Questionnaire, with lower values indication morning chronotypes and higher values evening chronotypes (Adapted from Sleep Med Rev. 11(6). Roenneberg T, Kuehnle T, Juda M, et al. Epidemiology of the human circadian clock. 429–438, Copyright 2007, with permission from Elsevier). During adolescence, studies have shown a significant phase shift towards evening types. This phase delay is more important and lasts longer in boys compared to girls.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Meltzer LJ, Williamson AA, Mindell JA. Pediatric sleep health: it matters, and so does how we define it. Sleep Med Rev. 2021;57:101425. doi:10.1016/j.smrv.2021.101425 - DOI - PMC - PubMed
    1. Hirshkowitz M, Whiton K, Albert SM, et al. National Sleep Foundation’s updated sleep duration recommendations: final report. Sleep Health. 2015;1(4):233–243. doi:10.1016/j.sleh.2015.10.004 - DOI - PubMed
    1. Meltzer LJ, Plaufcan MR, Thomas JH, Mindell JA. Sleep problems and sleep disorders in pediatric primary care: treatment recommendations, persistence, and health care utilization. J Clin Sleep Med JCSM off Publ Am Acad Sleep Med. 2014;10(4):421–426. doi:10.5664/jcsm.3620 - DOI - PMC - PubMed
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth ed. American Psychiatric Association; 2013. doi:10.1176/appi.books.9780890425596 - DOI
    1. American Academy of Sleep Medicine. International Classification of Sleep Disorders; 2014.