Abstract
Robust clinical evidence has not been available for melatonin, a drug commonly administered for treating sleep problems of children with autism spectrum disorder (ASD). In a phase 3 randomized, placebo-controlled clinical trial, we administered 1-mg melatonin (n = 65), 4-mg melatonin (n = 65), or placebo (n = 66) to196 children with ASD once daily before bedtime under adequate sleep hygiene interventions. The primary outcome was sleep onset latency (SOL) assessed with the electronic sleep diary. SOL shortened significantly in the 1- and 4-mg melatonin groups compared to the placebo group (− 22.0, − 28.0, and − 5.0 min, respectively; p < 0.0001 each). This therapeutic regimen of melatonin is a reasonable clinical approach to cope with ASD-emergent difficulties in children with ASD.
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Data Availability
The dataset used and/or analysed during the current study are available from the corresponding author upon reasonable request.
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Acknowledgments
The authors are grateful to all investigators and subinvestigators, and clinical research coordinators at respective medical institutions for child recruitment, data acquisition, and study conduct, to children along with their families for their participation in the present study, and to Satoshi Sakima, MD, for valuable discussions about the manuscript; his effort was compensated by Nobelpharma Co., Ltd.
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The present study was funded by Nobelpharma Co., Ltd.
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MH and KM conceived the study. MH, KM, MF, HT, YI, IH, HS, OY, and YY contributed to the study design and planning. IH made the analyses. MH prepared the first draft of the manuscript. MH and KM finalized the manuscript. All authors edited and contributed to the final version of the manuscript and gave final approval to the submitted version.
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The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. MH reported receiving consulting fees from Nobelpharma during the conduct of the study. KM reported receiving grants from the Japanese Ministry of Health, Labour and Welfare (H29-Seishin-Ippan-001, 19GC1012), the Japanese Ministry of Education, Science, and Technology, and the National Center of Neurology and Psychiatry Intramural Research Grant for Neurological and Psychiatric Disorders, consulting fees from Nobelpharma and Taisho Pharmaceutical, and lecture fees from Eisai, MSD, Takeda Pharmaceutical, Astellas Pharma, and Janssen Pharmaceutical. MF reported receiving grant support from Nobelpharma. YY reported receiving grant support from Nobelpharma. Nobelpharma Co., Ltd. is a company that provided the investigational drugs. HT is an employee of CMIC. YI, IH, HS, and OY are employees of Nobelpharma Co., Ltd.
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This study was performed in accordance with the Declaration of Helsinki. Ethical approval was obtained from the institutional review board at each participating institution.
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Hayashi, M., Mishima, K., Fukumizu, M. et al. Melatonin Treatment and Adequate Sleep Hygiene Interventions in Children with Autism Spectrum Disorder: A Randomized Controlled Trial. J Autism Dev Disord 52, 2784–2793 (2022). https://doi.org/10.1007/s10803-021-05139-w
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DOI: https://doi.org/10.1007/s10803-021-05139-w