Melatonin versus placebo in the treatment of sleep disorders in children and adolescents with autism: Systematic review and meta-analysis
DOI:
https://doi.org/10.33448/rsd-v13i4.45540Keywords:
Insomnia; Children; Melatonin; Autism spectrum disorder; Clinical trial.Abstract
Objective: To systematically review the evidence on the use of melatonin in the treatment of sleep disorders in children and adolescents with autism spectrum disorder (ASD). Method: Systematic review of randomized controlled clinical trials on the use of melatonin and included children and adolescents with ASD and sleep disorders, searching MEDLINE, SCOPUS, Web of science, Cochrane Central Register Controlled Trials, in the period between September and October 2023. The selection of studies were carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Changes in Total Sleep Time (TST) and Sleep Latency (SL) measurements were statistically significant. The 95% CI of 1.66 [1.10, 2.23] and 2.55 [1.02, 4.08] showed an increase in TST with the use of the intervention. (p < 0.00001) [18, 19]. Garstang showed a statistical difference with the use of melatonin, with the result of 95% CI of -5.96 [-8.77, -3.16], as well as Cortesi with a 95% CI of -1.23 [-1.75, - 0.70] and Gringras with -1.35 [-1.79, -0.91], with reduced latency to start sleep (p = 0.0002). Conclusions: Larger samples are needed to evaluate the effectiveness of melatonin on other sleep patterns, such as nighttime awakenings and sleep quality.
References
Allik, H., Larsson, J. O., & Smedje, H. (2006) Sleep Patterns of School-Age Children with Asperger Syndrome or High-Functioning Autism. Journal of Autism and Developmental Disorders. 36(5), 585–95.
Andersen, I. M., Kaczmarska, J., McGrew, S. G., & Malow, B. A. (2008) Melatonin for Insomnia in Children With Autism Spectrum Disorders. Journal of Child Neurology. 23(5), 482–5.
Cortesi, F., Giannotti, F., Sebastiani, T., Panunzi, S., & Valente, D. (2012) Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: a randomized placebo-controlled trial. Journal of Sleep Research. 21(6), 700–9.
Cuomo, B. M., Vaz, S., Lee, E. A. L., Thompson, C., Rogerson, J. M., & Falkmer, T. (2017) Effectiveness of Sleep-Based Interventions for Children with Autism Spectrum Disorder: A Meta-Synthesis. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 37(5), 555–78.
European Medicines Agency. (2023). https://www.ema.europa.eu.
Garstang, J. & Wallis, M. (2006) Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child: Care, Health and Development. 32(5), 585–9.
Gringras, P., Nir, T., Breddy, J., Frydman-Marom, A., & Findling, R. L. (2017) Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder. Journal of the American Academy of Child & Adolescent Psychiatry. 56(11), 948-957.e4.
Hoffmann, T. C., Glasziou, P. P., Boutron, I., Milne, R., Perera, R., Moher, D., et al. (2014) Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ. 348(mar07 3), g1687–g1687.
Johnson, K. P., & Zarrinnegar, P. (2021) Autism Spectrum Disorder and Sleep. Child and Adolescent Psychiatric Clinics of North America. 30(1), 195–208.
Lalanne, S., Fougerou-Leurent, C., Anderson, G. M., Schroder, C. M., Nir, T., Chokron S., et al. (2021) Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder. International Journal of Molecular Sciences. 22(3), 1490.
Levin, A. & Scher, A. (2016) Sleep Problems in Young Children with Autism Spectrum Disorders: A Study of Parenting Stress, Mothers’ Sleep‐Related Cognitions, and Bedtime Behaviors. CNS Neuroscience & Therapeutics. 22(11), 921–7.
Malow, B. A., Byars, K., Johnson, K., Weiss, S., Bernal, P., Goldman, S. E., et al. (2012) A Practice Pathway for the Identification, Evaluation, and Management of Insomnia in Children and Adolescents With Autism Spectrum Disorders. Pediatrics. 1;130(2), S106–24.
Malow, B. A., Findling, R. L., Schroder, C. M., Maras, A., Breddy, J., Nir, T., et al. (2021) Sleep, Growth, and Puberty After 2 Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder. Journal of the American Academy of Child & Adolescent Psychiatry. 60(2), 252-261.e3.
Maras, A., Schroder, C. M., Malow, B. A., Findling, R. L., Breddy, J., Nir, T., et al. (2018) Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder. Journal of Child and Adolescent Psychopharmacology. 28(10), 699–710.
Melke, J., Goubran Botros, H., Chaste, P., Betancur, C., Nygren, G., Anckarsäter, H., et al. (2007) Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry. 13(1), 90–8.
Miano, S., Bruni, O., Elia, M., Trovato, A., Smerieri, A., Verrillo, E., et al. (2007) Sleep in children with autistic spectrum disorder: A questionnaire and polysomnographic study. Sleep Medicine. 9(1), 64–70.
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Medicine. 6(7), e1000097.
OPAS/OMS. (2023). Transtorno do espectro autista - OPAS/OMS. Organização Pan-Americana da Saúde. https://www.paho.org/pt/topicos/transtorno-do-espectro-autista
Paavonen, E. J, Nieminen-von Wendt, T., Vanhala, R., Aronen, E. T, von Wendt, L. (2003) Effectiveness of Melatonin in the Treatment of Sleep Disturbances in Children with Asperger Disorder. Journal of Child and Adolescent Psychopharmacology. 13(1), 83–95.
Polimeni, M., Richdale, A., Francis, A. (2007) The Impact of Children’s Sleep Problems on the Family and Behavioural Processes Related to their Development and Maintenance. E-Journal of Applied Psychology. 4;3(1).
Richdale, A. L & Schreck, K. A. (2009) Sleep problems in autism spectrum disorders: Prevalence, nature, & possible biopsychosocial aetiologies. Sleep Medicine Reviews. 13(6), 403–11.
Rossignol, D. A & Frye, R. E. (2011) Melatonin in autism spectrum disorders: a systematic review and meta‐analysis. Developmental Medicine & Child Neurology. 19;53(9), 783–92.
Schroder, C. M, Malow, B. A, Maras, A., Melmed, R. D, Findling, R. L, Breddy, J., et al. (2019) Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver’s Quality of Life. Journal of Autism and Developmental Disorders. 11;49(8), 3218–30.
Schröder, C. M, Broquère, MA, Claustrat, B., Delorme, R., Franco, P., Lecendreux, M., et al. (2022) Approches thérapeutiques des troubles du sommeil et des rythmes chez l’enfant avec TSA. L’Encéphale. 48(3), 294–303.
Sterne, JAC, Savović, J., Page, MJ, Elbers, RG, Blencowe, NS, Boutron, I., et al. (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 28, l4898.
Tordjman, S., Anderson, G. M, Bellissant, E., Botbol M., Charbuy, H., Camus, F., et al. (2012) Day and nighttime excretion of 6-sulphatoxymelatonin in adolescents and young adults with autistic disorder. Psychoneuroendocrinology. 37(12), 1990–7.
Tordjman, S., Anderson, G. M, Pichard, N., Charbuy, H., & Touitou, Y. (2005) Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biological Psychiatry. 57(2), 134–8.
Veatch, O. J, Pendergast, J. S, Allen, M. J, Leu, R. M, Johnson, C. H, Elsea, S. H, et al. (2014) Genetic Variation in Melatonin Pathway Enzymes in Children with Autism Spectrum Disorder and Comorbid Sleep Onset Delay. Journal of Autism and Developmental Disorders. 45(1), 100–10.
Wright, B., Sims, D., Smart, S., Alwazeer, A., Alderson-Day, B., Allgar, V., et al. (2010) Melatonin Versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial. Journal of Autism and Developmental Disorders. 41(2), 175–84.
Xiong, M., Li, F., Liu, Z., Xie, X., Shen, H., Li, W., et al. (2023) Efficacy of Melatonin for Insomnia in Children with Autism Spectrum Disorder: A Meta-analysis. Neuropediatrics. 54(03), 167–73.
Zaidan, R., Geoffriau, M., Brun, J., Taillard, J., Bureau, C., Chazot, G., et al. (1994) Melatonin Is Able to Influence Its Secretion in Humans: Description of a Phase-Response Curve. Neuroendocrinology. 60(1), 105–12.
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