Melatonin in autism spectrum disorders: a systematic review and meta-analysis
Open accessAbstract
AIM: The aim of this study was to investigate melatonin-related findings in autism spectrum disorders (ASD), including autistic disorder, Asperger syndrome, Rett syndrome, and pervasive developmental disorders, not otherwise specified. METHOD: Comprehensive searches were conducted in the PubMed, Google Scholar, CINAHL, EMBASE, Scopus, and ERIC databases from their inception to October 2010. Two reviewers independently assessed 35 studies that met the inclusion criteria. Of these, meta-analysis was performed on five randomized double-blind, placebo-controlled studies, and the quality of these trials was assessed using the Downs and Black checklist. RESULTS: Nine studies measured melatonin or melatonin metabolites in ASD and all reported at least one abnormality, including an abnormal melatonin circadian rhythm in four studies, below average physiological levels of melatonin and/or melatonin derivates in seven studies, and a positive correlation between these levels and autistic behaviors in four studies. Five studies reported gene abnormalities that could contribute to decreased melatonin production or adversely affect melatonin receptor function in a small percentage of children with ASD. Six studies reported improved daytime behavior with melatonin use. Eighteen studies on melatonin treatment in ASD were identified; these studies reported improvements in sleep duration, sleep onset latency, and night-time awakenings. Five of these studies were randomized double-blind, placebo-controlled crossover studies; two of the studies contained blended samples of children with ASD and other developmental disorders, but only data for children with ASD were used in the meta-analysis. The meta-analysis found significant improvements with large effect sizes in sleep duration (73 min compared with baseline, Hedge's g 1.97 [95% confidence interval {CI} CI 1.10-2.84], Glass's Δ 1.54 [95% CI 0.64-2.44]; 44 min compared with placebo, Hedge's g 1.07 [95% CI 0.49-1.65], Glass's Δ 0.93 [95% CI 0.33-1.53]) and sleep onset latency (66 min compared with baseline, Hedge's g-2.42 [95% CI -1.67 to -3.17], Glass's Δ-2.18 [95% CI -1.58 to -2.76]; 39 min compared with placebo, Hedge's g-2.46 [95% CI -1.96 to -2.98], Glass's Δ-1.28 [95% CI -0.67 to -1.89]) but not in night-time awakenings. The effect size varied significantly across studies but funnel plots did not indicate publication bias. The reported side effects of melatonin were minimal to none. Some studies were affected by limitations, including small sample sizes and variability in the protocols that measured changes in sleep parameters. INTERPRETATION: Melatonin administration in ASD is associated with improved sleep parameters, better daytime behavior, and minimal side effects. Additional studies of melatonin would be helpful to confirm and expand on these findings.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Out of 18 studies, the average overall improvement rate from melatonin for sleep disturbances in individuals with ASD was over 84%.
“Out of 18 studies, the average overall improvement rate from melatonin for sleep disturbances in individuals with ASD was over 84% [58].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [58]
Children with ASD have lower urinary melatonin secretion than typical children, suggesting possibly lower production levels.
“Children with ASD have lower urinary melatonin secretion than typical children, suggesting possibly lower production levels [57, 58].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [58]
Sleep abnormalities affect 80% of children with ASD and range from reduced sleep duration to parasomnias.
“Sleep abnormalities affect 80% of children with ASD and range from reduced sleep duration to parasomnias 2627.”
From Gastrointestinal Issues and Autism Spectrum Disorder (2020) · cites this paper as [26]
Cited by
Sorted by citations
Autism Spectrum Disorder: A Review
Hirota, T., & King, B. H. (2023) · JAMA · doi:10.1001/jama.2022.23661 · Cited by 957 · see citing works
New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation
Zisapel, N. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14116 · Cited by 893 · see citing works
“The use of melatonin for treating chronic sleep–wake cycle disorders of children with ASD/NGD is increasing (Rossignol and Frye, 2011; Cortesi et al., 2012; Gringras et al., 2012; 2017; Malow et al., 2012; Cuomo et al., 2017).”
BackgroundWilson, S., Nutt, D., Alford, C., Argyropoulos, S., Baldwin, D., Bateson, A., Britton, T., Crowe, C., Dijk, D.-J., Espie, C., et al. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881110379307 · Cited by 634 · see citing works
The relationship between sleep and behavior in autism spectrum disorder (ASD): a review
Cohen, S., Conduit, R., Lockley, S. W., Rajaratnam, S. M., & Cornish, K. M. (2014) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-6-44 · Cited by 389 · see citing works
“In contrast, studies have suggested that melatonin is only effective for children with ASD who have difficulties with sleep latency, as it is known to increase night awakenings and disrupt sleep maintenance [55].”
BackgroundSystematic Review and Meta-Analysis of Behavioral Interventions for Pediatric Insomnia
Meltzer, L. J., & Mindell, J. A. A. (2014) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsu041 · Cited by 384 · see citing works
“…published metaanalyses in these populations focusing instead on subjective and objective sleep parameters in those with ADHD (Cortese, Faraone, Konofal, & Lecendreux, 2009) or the use of melatonin as a treatment for insomnia in youth with autism (Guenole & Baleyte, 2011; Rossignol & Frye, 2011).”
Rossignol, D. A., & Frye, R. E. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00150 · Cited by 369 · see citing works
“…Fahmy et al., 2013), reduce oxidative stress (Dolske et al., 1993; Chez et al., 2002; Adams and Holloway, 2004; Rossignol, 2009; Adams et al., 2011; Rossignol and Frye, 2011; Hardan et al., 2012; Ghanizadeh and MoghimiSarani, 2013), and decrease inflammation (Stefanatos et al., 1995; Shenoy et…”
BackgroundSelf-citationHowes, O. D., Rogdaki, M., Findon, J. L., Wichers, R. H., Charman, T., King, B. H., Loth, E., McAlonan, G. M., McCracken, J. T., Parr, J. R., et al. (2018) · Journal of Psychopharmacology · doi:10.1177/0269881117741766 · Cited by 342 · see citing works
“A meta-analysis of five small studies supports the use of melatonin for sleep disorder in ASD (Rossignol and Frye, 2011) (evidence level Ia).”
BackgroundMethodInfluentialWilson, S., Anderson, K., Baldwin, D., Dijk, D.-J., Espie, A., Espie, C., Gringras, P., Krystal, A., Nutt, D., Selsick, H., et al. (2019) · Journal of Psychopharmacology · doi:10.1177/0269881119855343 · Cited by 312 · see citing works
“, 2003) or delayed sleep phase syndrome and learning difficulties, autism and ADHD (Gringras et al., 2017; Maras et al., 2018; Rossignol and Frye, 2011; van der Heijden et al., 2007) is increasingly robust.”
BackgroundGringras, P., Nir, T., Breddy, J., Frydman-Marom, A., & Findling, R. L. (2017) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2017.09.414 · Cited by 306 · see citing works
Current role of melatonin in pediatric neurology: Clinical recommendations
Bruni, O., Alconada, D. A., Besag, F., Biran, V., Braam, W., Cortese, S., Moavero, R., Parisi, P., Smits, M. G., van der Heijden, K. B., et al. (2014) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2014.12.007 · Cited by 278 · see citing works
“The majority of children with ASD responded to a dose of 1e3 mg given 30 min before bedtime, with improvement in sleep latency and total sleep duration.(67,69) The overall improvement rate with melatonin was 80%.”
BackgroundInfluentialMarotta, R., Risoleo, M. C., Messina, G., Parisi, L., Carotenuto, M., Vetri, L., & Roccella, M. (2020) · Brain Sciences · doi:10.3390/brainsci10030163 · Cited by 279 · see citing works
“[134] The use of melatonin for the treatment of chronic sleep-wake cycle disorders in children with autism is constantly increasing [135].”
BackgroundMalow, B., Adkins, K. W., McGrew, S. G., Wang, L., Goldman, S. E., Fawkes, D., & Burnette, C. (2012) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1418-3 · Cited by 274 · see citing works
“Three recent reviews have been published on the use of melatonin for insomnia in children with ASD (Doyen et al. 2011; Rossignol and Frye 2011; Guénolé et al. 2011).”
BackgroundResultSignalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 272 · see citing works
“In addition, a meta-analysis and some placebo-controlled studies have suggested that melatonin supplementation may also have positive effects on autistic behavioural disorders.(481,486) One study on VPA-treated rats has proven that melatonin treatment significantly improves social behavioural deficits through CaMKII/P…”
BackgroundGevi, F., Zolla, L., Gabriele, S., & Persico, A. M. (2016) · Molecular Autism · doi:10.1186/s13229-016-0109-5 · Cited by 251 · see citing works
“Its well-known role in circadian rhythmicity makes it an ideal candidate to explain the frequent occurrence, especially at the onset of ASD and during early infancy, of sleep disorders highly responsive to melatonin as a pharmacological therapy [56].”
BackgroundNeuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder
Usui, N., Kobayashi, H., & Shimada, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065487 · Cited by 267 · see citing works
“In randomized, double-blind, placebocontrolled trials, melatonin treatment, acting as a potent antioxidant, improved daytime behavior in ASD patients [162].”
BackgroundAutism spectrum disorder: advances in evidence-based practice
Anagnostou, E. A., Zwaigenbaum, L., Szatmári, P., Fombonne, E. J., Fernandez, B. A., Woodbury‐Smith, M., Brian, J. A., Bryson, S. E., Smith, I. M., Drmic, I., et al. (2014) · Canadian Medical Association Journal · doi:10.1503/cmaj.121756 · Cited by 234 · see citing works
Environmental Factors in Autism
Grabrucker, A. M. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2012.00118 · Cited by 237 · see citing works
“pineal gland and levels of melatonin or melatonin derivatives were found to be often below average in individuals with ASD (Rossignol and Frye, 2011).”
BackgroundInfluentialCarmassi, C., Palagini, L., Caruso, D., Masci, I., Nobili, L., Vita, A., & Dell’Osso, L. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00366 · Cited by 220 · see citing works
Oxidative Stress and Immune System Dysfunction in Autism Spectrum Disorders
Pangrazzi, L., Balasco, L., & Bozzi, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093293 · Cited by 219 · see citing works
“In several studies, melatonin treatment improved daytime behavior in individuals with ASD [105].”
BackgroundGringras, P., Gamble, C. L., Jones, A. P., Wiggs, L. D., Williamson, P. R., Sutcliffe, A. G., Montgomery, P., Whitehouse, W. P., Choonara, I., Allport, T., et al. (2012) · BMJ · doi:10.1136/bmj.e6664 · Cited by 218 · see citing works
A Short Review on the Current Understanding of Autism Spectrum Disorders
Park, H. R., Lee, J. M., Moon, H. E., Lee, D. S., Kim, B.-N., Kim, J., Kim, D. G., & Paek, S. H. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.1.1 · Cited by 214 · see citing works
“Abnormal melatonin synthesis [146, 147]”
Sleep patterns in children with autistic spectrum disorders: a prospective cohort study
Humphreys, J. S., Gringras, P., Blair, P. S., Scott, N., Henderson, J., Fleming, P. J., & Emond, A. M. (2014) · Archives of Disease in Childhood · doi:10.1136/archdischild-2013-304083 · Cited by 197 · see citing works
Sleep in Children with Neurodevelopmental Disabilities
Angriman, M., Caravale, B., Novelli, L., Ferri, R., & Bruni, O. (2015) · Neuropediatrics · doi:10.1055/s-0035-1550151 · Cited by 192 · see citing works
“86 Therefore, patients with ASD may be unable to fall asleep until late at night or may exhibit irregular sleep – wake rhythms with multiple naps distributed through day and night.”
Hardeland, R. (2012) · Europe PMC (PubMed Central) · Cited by 202 · see citing works
Biomarkers in autism spectrum disorder: the old and the new
Ruggeri, B., Sarkans, U., Schumann, G., & Persico, A. M. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3290-7 · Cited by 191 · see citing works
Autism Spectrum Disorder: Primary Care Principles.
Sanchack, K. E., & Thomas, C. (2016) · PubMed · Cited by 184 · see citing works
Tye, C., Runicles, A. K., Whitehouse, A. J. O., & Alvares, G. A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00751 · Cited by 177 · see citing works
“The 35 summary evidence for melatonin supplementation for sleep problems in ASD suggests significantly 36 improved sleep duration and sleep onset latency compared to placebo, and significantly improved 37 daytime behaviours, with minimal side effects (106,107).”
BackgroundMaras, A., Schroder, C. M., Malow, B. A., Findling, R. L., Breddy, J., Nir, T., Shahmoon, S., Zisapel, N., & Gringras, P. (2018) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2018.0020 · Cited by 176 · see citing works
“Melatonin treatment has shown promise in the treatment of insomnia in children with neurodevelopmental disabilities (Rossignol and Frye 2011; Cortesi et al. 2012; Gringras et al. 2012).”
BackgroundMinich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
“A review article found that patients with autism had improved sleep parameters, better daytime behavior, and minimal side effects with melatonin use [119].”
BackgroundMalow, B. A., Findling, R. L., Schroder, C. M., Maras, A., Breddy, J., Nir, T., Zisapel, N., & Gringras, P. (2020) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2019.12.007 · Cited by 174 · see citing works
“28 However, gradual loss of effect of exogenous melatonin, which is to be expected with poor CYP1A2 metabolism, 28 was observed in only 1 participant on a 10-mg dose and resolved by decreasing the dose to the 5 mg used before dose escalation.”
Sleep patterns in children with and without autism spectrum disorders: Developmental comparisons
Hodge, D., Carollo, T. M., Lewin, M., Hoffman, C. D., & Sweeney, D. P. (2014) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2014.03.037 · Cited by 171 · see citing works
Cuomo, B., Vaz, S. M. A., Lee, E. A. L., Thompson, C., Rogerson, J. M., & Falkmer, T. (2017) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1920 · Cited by 170 · see citing works
Autism spectrum disorders: an overview on diagnosis and treatment
Brentani, H., Paula, C. S., Bordini, D., Rolim, D., Sato, F. P., Portolese, J., Pacífico, M. C., & McCracken, J. T. (2013) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2013-s104 · Cited by 173 · see citing works
The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders
Pagan, C., Delorme, R., Callebert, J., Goubran-Botros, H., Amsellem, F., Drouot, X., Boudebesse, C., Le Dudal, K., Ngo-Nguyen, N., Laouamri, H., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.120 · Cited by 165 · see citing works
Melatonin Supplementation for Children With Atopic Dermatitis and Sleep Disturbance
Chang, Y.-S., Lin, M.-H., Lee, J., Lee, P., Dai, Y., Chu, K., Sun, C. H., Lin, Y., Wang, L., Yu, H., et al. (2015) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2015.3092 · Cited by 167 · see citing works
Autism as a Disorder of Biological and Behavioral Rhythms: Toward New Therapeutic Perspectives
Tordjman, S., Davlantis, K. S., Georgieff, N., Geoffray, M., Speranza, M., Anderson, G. M., Xavier, J., Botbol, M., Oriol, C., Bellissant, É., et al. (2015) · Frontiers in Pediatrics · doi:10.3389/fped.2015.00001 · Cited by 162 · see citing works
Tse, A. C. Y., Lee, P. H., Chan, K. K. S., Edgar, V. B., Wilkinson-Smith, A., & Lai, W. H. E. (2019) · Autism · doi:10.1177/1362361318823910 · Cited by 164 · see citing works
“Secretion of melatonin normally increases shortly after dark, peaks in the middle of the night, and falls slowly during early morning hours (Rossignol & Frye, 2011).”
BackgroundBesag, F., Vasey, M. J., Lao, K. S. J., & Wong, I. C. K. (2019) · CNS Drugs · doi:10.1007/s40263-019-00680-w · Cited by 170 · see citing works
Gastrointestinal Issues and Autism Spectrum Disorder
Madra, M., Ringel, R., & Margolis, K. G. (2020) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2020.02.005 · Cited by 159 · see citing works
Pediatric Integrative Medicine
McClafferty, H. H., Vohra, S., Bailey, M. L., Brown, M. L., Esparham, A. E., Gerstbacher, D., Golianu, B. J., Niemi, A., Sibinga, E. M. S., Weydert, J. A., et al. (2017) · PEDIATRICS · doi:10.1542/peds.2017-1961 · Cited by 155 · see citing works
Interactions of the serotonin and circadian systems: nature and nurture in rhythms and blues
Ciarleglio, C. M., Resuehr, H. E. S., & McMahon, D. G. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.09.036 · Cited by 151 · see citing works
Smolensky, M. H., Sackett-Lundeen, L. L., & Portaluppi, F. (2015) · Chronobiology International · doi:10.3109/07420528.2015.1072002 · Cited by 153 · see citing works
Therapeutic Effects of Melatonin Receptor Agonists on Sleep and Comorbid Disorders
Laudon, M., & Frydman‐Marom, A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150915924 · Cited by 150 · see citing works
“in children with autism spectrum disorder and some neurogenetic disorders have also been linked to insufficient or abnormal melatonin rhythms [12–15].”
BackgroundBhandari, R., Paliwal, J. K., & Kuhad, A. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-30402-7_4 · Cited by 156 · see citing works
Frye, R. E., Rose, S., Slattery, J. M., & MacFabe, D. F. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.27458 · Cited by 142 · see citing works
“Melatonin is widely used for assisting with sleep initiation in children with ASD and has been shown to be effective for improving sleep in several controlled clinical trials (238, 239).”
BackgroundSelf-citationInsomnia, parasomnias, and narcolepsy in children: clinical features, diagnosis, and management
Maski, K. P., & Owens, J. A. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30204-6 · Cited by 139 · see citing works
Tordjman, S., Najjar, I., Bellissant, E., Anderson, G., Barburoth, M., Cohen, D., Jaafari, N., Schischmanoff, O., Fagard, R., Lagdas, E., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141020508 · Cited by 132 · see citing works
“Frye, 2011 [80] Dev.”
Schroder, C. M., Malow, B. A., Maras, A., Melmed, R. D., Findling, R. L., Breddy, J., Nir, T., Shahmoon, S., Zisapel, N., & Gringras, P. (2019) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-019-04046-5 · Cited by 133 · see citing works
Safety of higher doses of melatonin in adults: A systematic review and meta-analysis
Menczel Schrire, Z., Phillips, C. L., Chapman, J. L., Duffy, S. L., Wong, G., D’Rozario, A. L., Comas, M., Raisin, I., Saini, B., Gordon, C. J., et al. (2022) · Journal of Pineal Research · doi:10.1111/jpi.12782 · Cited by 133 · see citing works
Goldman, S. E., Adkins, K. W., Calcutt, M. W., Carter, M. D., Goodpaster, R. L., Wang, L., Shi, Y., Burgess, H. J., Hachey, D. L., & Malow, B. A. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2123-9 · Cited by 133 · see citing works
“…IL, USA D. L. Hachey Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA as a dietary supplement, has shown promise in reducing sleep latency in children with ASD in our work (Andersen et al. 2008; Malow et al. 2012) and in a recent review (Rossignol and Frye 2011).”
BackgroundResultTordjman, S., Anderson, G. M., Bellissant, E., Botbol, M., Charbuy, H., Camus, F., Graignic, R., Kermarrec, S., Fougerou, C., Cohen, D., et al. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.04.013 · Cited by 129 · see citing works
“, 2005 for reviews), as well as beneficial effects of melatonin when administered to individuals with autism and sleep problems (Doyen et al., 2011; Rossignol and Frye, 2011; Guénolé et al., 2011).”
Sleep in autism Spectrum disorder and attention deficit hyperactivity disorder
Singh, K., & Zimmerman, A. W. (2015) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2015.03.006 · Cited by 126 · see citing works
Primary Care for Adults on the Autism Spectrum
Nicolaidis, C., Kripke, C. C., & Raymaker, D. (2014) · Medical Clinics of North America · doi:10.1016/j.mcna.2014.06.011 · Cited by 128 · see citing works
Pediatric sleep disturbances and treatment with melatonin
Esposito, S., Laino, D., D’Alonzo, R., Mencarelli, A., Genova, L. D., Fattorusso, A., Argentiero, A., & Mencaroni, E. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-1835-1 · Cited by 121 · see citing works
Abdelgadir, I. S., Gordon, M. A., & Akobeng, A. K. (2018) · Archives of Disease in Childhood · doi:10.1136/archdischild-2017-314181 · Cited by 117 · see citing works
McGuire, K., Fung, L. K., Hagopian, L. P., Vasa, R. A., Mahajan, R., Bernal, P., Silberman, A. E., Wolfe, A. E., Coury, D. L., Hardan, A. Y., et al. (2016) · PEDIATRICS · doi:10.1542/peds.2015-2851l · Cited by 115 · see citing works
Weighted Blankets and Sleep in Autistic Children—A Randomized Controlled Trial
Gringras, P., Green, D., Wright, B., Rush, C., Sparrowhawk, M., Pratt, K., Allgar, V. L., Hooke, N., Moore, D. C., Zaiwalla, Z., et al. (2014) · PEDIATRICS · doi:10.1542/peds.2013-4285 · Cited by 113 · see citing works
Common neurological co-morbidities in autism spectrum disorders
Maski, K. P., Jeste, S., & Spence, S. J. (2011) · Current Opinion in Pediatrics · doi:10.1097/mop.0b013e32834c9282 · Cited by 112 · see citing works
Sleep in Autism Spectrum Disorders
Veatch, O. J., Maxwell-Horn, A. C., & Malow, B. A. (2015) · Current Sleep Medicine Reports · doi:10.1007/s40675-015-0012-1 · Cited by 114 · see citing works
“Given that the half-life of melatonin is rather short (<1 h), it is less effective for night wakings [97]; controlled-release melatonin preparations are sometimes effective for night wakings [98].”
Quintana, D. S., Westlye, L. T., Hope, S., Nærland, T., Elvsåshagen, T., Dørum, E., Rustan, Ø., Valstad, M., Rezvaya, L., Lishaugen, H., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.103 · Cited by 111 · see citing works
Assessment of Sleep in Children with Autism Spectrum Disorder
Moore, M., Evans, V., Hanvey, G. A., & Johnson, C. R. (2017) · Children · doi:10.3390/children4080072 · Cited by 106 · see citing works
“Differences have been observed in the mean plasma melatonin levels and the excretion of melatonin sulfate in children with ASD when compared to the levels observed in TD children in some studies [31,32], but not in others [33].”
BackgroundResultMelatonin and health: an umbrella review of health outcomes and biological mechanisms of action
Posadzki, P., Bajpai, R. C., Kyaw, B. M., Roberts, N., Brzezinski, A., Christopoulos, G. I., Divakar, U., Bajpai, S., Soljak, M., Dunleavy, G., et al. (2018) · BMC Medicine · doi:10.1186/s12916-017-1000-8 · Cited by 101 · see citing works
Cortese, S., Wang, F., Angriman, M., Masi, G., & Bruni, O. (2020) · CNS Drugs · doi:10.1007/s40263-020-00710-y · Cited by 101 · see citing works
A Review of Complementary and Alternative Treatments for Autism Spectrum Disorders
Lofthouse, N., Hendren, R. L., Hurt, E. A., Arnold, L. E., & Butter, E. M. (2012) · Autism Research and Treatment · doi:10.1155/2012/870391 · Cited by 98 · see citing works
“Rossignol and Frye [41] published a review and meta-analysis of 35 studies and reported that 9 studies of melatonin levels reported at least one sleep abnormality (7 low, 2 high, 4 circadian); 4 studies reported significant correlations between melatonin levels and ASD symptoms; and 5 studies reported gene abnormaliti…”
BackgroundFrye, R. E., & Rossignol, D. A. (2016) · Clinical Medicine Insights Pediatrics · doi:10.4137/cmped.s38337 · Cited by 96 · see citing works
Self-citationAppleton, R., Jones, A. P., Gamble, C. L., Williamson, P. R., Wiggs, L. D., Montgomery, P., Sutcliffe, A. G., Barker, C. E., & Gringras, P. (2012) · Health Technology Assessment · doi:10.3310/hta16400 · Cited by 96 · see citing works
Hyperactivity and male‐specific sleep deficits in the 16p11.2 deletion mouse model of autism
Angelakos, C. C., Watson, A. J., O'Brien, W. T., Krainock, K. S., Nickl‐Jockschat, T., & Abel, T. (2017) · Autism Research · doi:10.1002/aur.1707 · Cited by 83 · see citing works
“…total sleep time in some studies of ASD patients [Wright et al., 2011], but has little effect on mitigating other sleep disturbances [Cortesi, Giannotti, Sebastiani, Panunzi, & Valente, 2012; Malow et al., 2012] and may even increase night awakenings [Rossignol & Frye, 2011; Gringras et al., 2012].”
BackgroundSleep in Neurodevelopmental Disorders
Esbensen, A. J., & Schwichtenberg, A. J. (2016) · International review of research in developmental disabilities · doi:10.1016/bs.irrdd.2016.07.005 · Cited by 97 · see citing works
“Although the dose, duration, and elements of sleep affected by melatonin vary considerably across studies, the cumulative findings provide support for melatonin treatment (Doyen et al., 2011; Guénolé & Baleyte, 2011; Rossignol & Frye, 2011; Schwichtenberg & Malow, 2015).”
BackgroundAlam, M. S., Rashid, M. M., Roy, R., Faizabadi, A. R., Gupta, K. D., & Ahsan, M. M. (2022) · Bioengineering · doi:10.3390/bioengineering9110710 · Cited by 104 · see citing works
“• ASD is diagnosed mainly by interactive sessions, so it requires clinical experts to diagnose children near two years of age [11]; • It is difficult for the parents to visit the specialists, and the availability of such physicians is much lower in rural communities or underdeveloped countries [12]; • Parents who are…”
BackgroundRetractedMechanisms of Fluoride Toxicity: From Enzymes to Underlying Integrative Networks
Strunecká, A., & Strunecký, O. (2020) · Applied Sciences · doi:10.3390/app10207100 · Cited by 93 · see citing works
“Insomnia and sleep disorders occur in 50–80% of ASD patients [125,126].”
BackgroundMelatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder
Lalanne, S., Fougerou-Leurent, C., Anderson, G. M., Schroder, C. M., Nir, T., Chokron, S., Delorme, R., Claustrat, B., Bellissant, E., Kermarrec, S., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031490 · Cited by 90 · see citing works
“metaanalysis of melatonin treatment in individuals with ASD [74] reported good tolerability (0.”
BackgroundInfluentialHsia, Y., Wong, A. Y. S., Murphy, D., Simonoff, E. A., Buitelaar, J. K., & Wong, I. C. K. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3263-x · Cited by 89 · see citing works
Autism Spectrum Disorder and Sleep
Johnson, K., & Zarrinnegar, P. (2020) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2020.08.012 · Cited by 87 · see citing works
Veatch, O. J., Pendergast, J. S., Allen, M. J., Leu, R. M., Johnson, C. H., Elsea, S. H., & Malow, B. A. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2197-4 · Cited by 86 · see citing works
“Melatonin supplementation is an emerging approach to treating ASD comorbid symptoms, including sleep initiation (Malow et al. 2012); however, some individuals are also nonresponders or exhibit disappearing effectiveness (Braam et al. 2010; Rossignol and Frye 2011).”
Autism Biomarkers: Challenges, Pitfalls and Possibilities
Anderson, G. M. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2225-4 · Cited by 82 · see citing works
“Over fifty papers have reported that redox status is altered or oxidative stress is increased in ASD (Frustaci et al. 2012; Rossignol and Frye 2011; Villagonzalo et al. 2010).”
BackgroundKhemakhem, A. M., Frye, R. E., El-Ansary, A. K., AL-Ayadhi, L. Y., & Bacha, A. G. B. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0085-2 · Cited by 84 · see citing works
Self-citationGut microbiota, kynurenine pathway and mental disorders – Review
Więdłocha, M., Marcinowicz, P., Janoska-Jaździk, M., & Szulc, A. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110145 · Cited by 87 · see citing works
Sleep in autism: A biomolecular approach to aetiology and treatment
Ballester, P., Richdale, A. L., Baker, E. K., & Peiró, A. M. (2020) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2020.101357 · Cited by 81 · see citing works
Parent-Implemented Bedtime Fading and Positive Routines for Children with Autism Spectrum Disorders
Delemere, E., & Dounavi, K. (2017) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-017-3398-4 · Cited by 80 · see citing works
“However melatonin lacks controlled research findings (Rossignol and Frye 2011).”
Low maternal melatonin level increases autism spectrum disorder risk in children
Braam, W., Ehrhart, F., Evelo, C. T., Maas, A. P. H. M., Smits, M. G., & Curfs, L. (2018) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2018.02.017 · Cited by 80 · see citing works
Pharmacotherapeutic management of sleep disorders in children with neurodevelopmental disorders
Bruni, O., Angriman, M., Melegari, M. G., & Ferri, R. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1674283 · Cited by 54 · see citing works
Approaches to studying and manipulating the enteric microbiome to improve autism symptoms
Frye, R. E., Slattery, J. M., MacFabe, D. F., Allen‐Vercoe, E., Parker, W., Rodakis, J., Adams, J. B., Krajmalnik‐Brown, R., Bolte, E. R., Kahler, S. G., et al. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.26878 · Cited by 75 · see citing works
“One of the most objective means for measuring sleep quality is actigraphy (87) that appears to be superior, especially for measuring nighttime wakening, as compared to parental sleep diaries (88).”
BackgroundSelf-citationClinical trials in autism spectrum disorder: evidence, challenges and future directions
Anagnostou, E. A. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000542 · Cited by 72 · see citing works
Autism spectrum disorder (ASD): Disturbance of the melatonin system and its implications
Wu, Z., Huang, S., Zou, J.-J., Wang, Q.-X., Naveed, M., Bao, H.-N., Wang, W., Fukunaga, K., & Han, F. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110496 · Cited by 72 · see citing works
Gastrointestinal Issues and Autism Spectrum Disorder
Madra, M., Ringel, R., & Margolis, K. G. (2021) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2020.11.006 · Cited by 71 · see citing works
Treatment strategies for complex behavioral insomnia in children with neurodevelopmental disorders
Grigg-Damberger, M. M., & Ralls, F. M. (2013) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e328365ab89 · Cited by 67 · see citing works
“Abnormally low levels of melatonin and/or its urinary metabolic derivatives have been found in ASD [18–20], and correlate with sleep problems and autistic behaviors [19].”
BackgroundPediatric sleep: current knowledge, gaps, and opportunities for the future
Reynolds, A., Spaeth, A. M., Hale, L. E., Williamson, A. A., LeBourgeois, M. K., Wong, S. D., Hartstein, L. E., Levenson, J. C., Kwon, M., Hart, C. N., et al. (2023) · SLEEP · doi:10.1093/sleep/zsad060 · Cited by 70 · see citing works
“Behavioral or medication trials [206] focused on improving sleep may include these measurements as biomarkers of treatment success.”
BackgroundGeoffroy, P. A., Micoulaud‐Franchi, J., Lopez, R., & Schroder, C. M. (2019) · L Encéphale · doi:10.1016/j.encep.2019.04.068 · Cited by 64 · see citing works
Systematic review and guide to management of core and psychiatric symptoms in youth with autism
Ameis, S. H., Kassee, C., Corbett-Dick, P., Cole, L. L., Dadhwal, S., Lai, M., Veenstra-VanderWeele, J. M., & Correll, C. U. (2018) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12918 · Cited by 64 · see citing works
“Additional systematic reviews (199, 200) also found some evidence for the efficacy of melatonin in ASD, with little to no adverse events reported (199, 200).”
BackgroundMelatonin Treatment in Children with Developmental Disabilities
Schwichtenberg, A. J., & Malow, B. A. (2015) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2015.02.008 · Cited by 65 · see citing works
Melatonin and Melatonin Agonists as Adjunctive Treatments in Bipolar Disorders
Geoffroy, P. A., Étain, B., Micoulaud‐Franchi, J., Bellivier, F., & Ritter, P. S. (2015) · Current Pharmaceutical Design · doi:10.2174/1381612821666150619093448 · Cited by 65 · see citing works
Tryptophan status in autism spectrum disorder and the influence of supplementation on its level
Kałużna‐Czaplińska, J., Jóźwik-Pruska, J., Chirumbolo, S., & Bjørklund, G. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0045-x · Cited by 65 · see citing works
“Melatonin is responsible for the regulation of circadian rhythms (Rossignol and Frye 2011).”
BackgroundTreatment for Sleep Problems in Children with Autism and Caregiver Spillover Effects
Tilford, J. M., Payakachat, N., Kuhlthau, K. A., Pyne, J. M., Kovacs, E. A., Bellando, J. B., Williams, D. K., Brouwer, W. B. F., & Frye, R. E. (2015) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-015-2507-5 · Cited by 65 · see citing works
“…and chronobiotic properties, is an approved US Food and Drug Administration nutrition supplement that showed promising results in small, randomized controlled trials as a monotherapy or combination with parent-based sleep education (Rossignol and Frye 2011; Cortesi et al. 2012; Malow et al. 2012a).”
Self-citationPharmacotherapy of autism spectrum disorders
Benvenuto, A., Battan, B., Porfirio, M. C., & Curatolo, P. (2012) · Brain and Development · doi:10.1016/j.braindev.2012.03.015 · Cited by 61 · see citing works
“Melatonin administration in ASDs is reported to be safe, well tolerated and efficient in improving sleep parameters and daytime behavior, and in decreasing of parental stress [18,19].”
BackgroundVargason, T., Frye, R. E., McGuinness, D. L., & Hahn, J. (2019) · Autism Research · doi:10.1002/aur.2128 · Cited by 59 · see citing works
“Detecting and treating COCs can have a significant impact on the clinical course of the child; for example, improving sleep can improve the quality of life of the whole family [Tilford et al., 2015] and improve behavioral problems during the day [Rossignol & Frye, 2011].”
BackgroundSelf-citationChronic Administration of Melatonin: Physiological and Clinical Considerations
Givler, D., Givler, A., Luther, P. M., Wenger, D. M., Ahmadzadeh, S., Shekoohi, S., Edinoff, A. N., Dorius, B. K., Baptiste, C. J., Cornett, E. M., et al. (2023) · Neurology International · doi:10.3390/neurolint15010031 · Cited by 59 · see citing works
Esposito, D., Belli, A., Ferri, R., & Bruni, O. (2020) · Brain Science · doi:10.3390/brainsci10070441 · Cited by 49 · see citing works
“Its circulating levels have been shown to be lower in autistic patients than controls [148,149] and recent studies suggest that high oxidative stress might contribute to the worsening of sleep disorders and behavioral symptoms in ASD individuals [88,150].”
BackgroundEffects of exercise on sleep, melatonin level, and behavioral functioning in children with autism
Tse, A. C. Y., Lee, P. H., Zhang, J., Chan, R., Ho, A. W., & Lai, E. W. (2022) · Autism · doi:10.1177/13623613211062952 · Cited by 55 · see citing works
“Many studies have also shown that melatonin supplement positively impacts sleep in children with ASD, including reduced sleep onset latency, increased total sleep duration, and improved SE (Rossignol & Frye, 2011).”
BackgroundLamy, M., & Erickson, C. A. (2018) · Current problems in pediatric and adolescent health care · doi:10.1016/j.cppeds.2018.08.015 · Cited by 58 · see citing works
Rzepka-Migut, B., & Paprocka, J. (2020) · Brain Sciences · doi:10.3390/brainsci10040219 · Cited by 55 · see citing works
- Authors
- ROSSIGNOL, D. A., & FRYE, R. E.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Corresponding author
- ROSSIGNOL, DANIEL A
- Venue
- Developmental Medicine & Child Neurology
- Publisher
- Wiley
- Published
- 2011-04-19
- Volume
- 53
- Issue
- 9
- Pages
- 783-792
- ISSN
- 0012-1622 (ISSN-L)
- 1469-8749
- OpenAlex
- W2045069726
- Cited by
- 468
- References
- 0
- Citations by year
- 2026: 16 · 2025: 32 · 2024: 28 · 2023: 39 · 2022: 49 · 2021: 32 · 2020: 43 · 2019: 31 · 2018: 27 · 2017: 28 · 2016: 31 · 2015: 30 · 2014: 36 · 2013: 26 · 2012: 12
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Developmental Medicine & Child Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- melatonin, autism spectrum disorder, sleep disorders, sleep duration, sleep latency, nocturnal awakenings, melatonin metabolites, melatonin treatment
- MeSH terms
- Child, Child Development Disorders, Pervasive, Child, Preschool, Double-Blind Method, Humans, Melatonin, Randomized Controlled Trials as Topic, Databases, Factual
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
