Cited by 471Autism Spectrum Disorder ResearchCircadian rhythm and melatoninSleep and related disorders

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Melatonin in autism spectrum disorders: a systematic review and meta-analysis

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ROSSIGNOL, DANIEL A, FRYE, RICHARD E·2011·Developmental Medicine & Child Neurology

DOI 10.1111/j.1469-8749.2011.03980.x

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Abstract

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.

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Result
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Self-citation
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“6 26 27 For these theoretical reasons, children with neurodevelopmental disorders may benefit from melatonin.”
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“These findings have been replicated in a number of systematic reviews, reports, and experimental studies (e.g., Carnett et al., 2020; Gringras et al., 2017; McLay et al., 2021; Rigney et al., 2018; Rossignol & Frye, 2011).”
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“Atypical antipsychotics, for example, have some evidence for reducing irritability, aggression, and repetitive behaviors(6); attention-deficit/ hyperactivity disorder (ADHD) medications (for ADHD-like behaviors or a comorbid ADHD diagnosis) have been shown to moderately improve hyperactivity symptoms(7); and melatonin…”
Background
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“…amount of MT is eaten for a long time, there may be certain side effects, such as morning drowsiness, vivid dreams, headache and dizziness (Korkmaz et al., 2009; Jung-Hynes et al., 2010; Rossignol and Frye, 2011; Por ﬁ rio et al., 2017; Posadzki et al., 2018; Xu et al., 2020; Duan et al., 2021).”
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“The relationship between daytime behaviours and better night-time management of children with ASD who underwent exogenous treatment with melatonin supplements was previously reported [2,3].”
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Authors: ROSSIGNOL, D. A., & FRYE, R. E.
Affiliations: The University of Texas Health Science Center at Houston (US)
Corresponding author: ROSSIGNOL, DANIEL A
ORCID: ROSSIGNOL, DANIEL A
FRYE, RICHARD E
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
DOI: 10.1111/j.1469-8749.2011.03980.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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

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Melatonin in autism spectrum disorders: a systematic review and meta-analysis

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