Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes.

Sleep Disorders Division, Department of Neurology and Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Journal of Autism and Developmental Disorders (Impact Factor: 3.06). 12/2011; 42(8):1729-37; author reply 1738. DOI: 10.1007/s10803-011-1418-3
Source: PubMed

ABSTRACT Supplemental melatonin has shown promise in treating sleep onset insomnia in children with autism spectrum disorders (ASD). Twenty-four children, free of psychotropic medications, completed an open-label dose-escalation study to assess dose-response, tolerability, safety, feasibility of collecting actigraphy data, and ability of outcome measures to detect change during a 14-week intervention. Supplemental melatonin improved sleep latency, as measured by actigraphy, in most children at 1 or 3 mg dosages. It was effective in week 1 of treatment, maintained effects over several months, was well tolerated and safe, and showed improvement in sleep, behavior, and parenting stress. Our findings contribute to the growing literature on supplemental melatonin for insomnia in ASD and inform planning for a large randomized trial in this population.

  • Side Effects of Drugs Annual 36, 36 edited by Sidhartha D. Ray, 01/2014: chapter 43: pages 659-673; Elsevier., ISBN: 978-0-444-63407-8
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    ABSTRACT: Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex-and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD. Translational Psychiatry (2014) 4, e●●; doi:10.1038/tp.2014.120; published online xx xxx 2014 INTRODUCTION Autism spectrum disorders (ASDs) are complex, heterogeneous and multifactorial disorders characterized by impaired social communication and repetitive/stereotyped behaviors. The diag-nosis of ASD currently relies entirely on patient clinical evaluation.
    Translational psychiatry. 10/2014; 4.
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    ABSTRACT: Background: Autism is known to be associated with hyperserotoninemia and, more recently, with decreased blood melatonin level. Melatonin is a neurohormone synthesized from serotonin and involved in circadian rhythms and sleep regulations. Thus, serotonin and melatonin are two ends of a biochemical pathway, and little is known concerning all the steps of this pathway in patients with Autism Spectrum Disorders. Moreover, the clinical relevance of these biochemical endophenotypes remains to be determined. Objectives: Here we explore the serotonin-melatonin pathway in a large cohort of patients with ASD, in order to (i) better characterize the biochemical abnormalities of this pathway in ASD, (ii) determine the clinical correlates of these biochemical abnormalities, and (iii) assess the relevance of these biochemical parameters as biomarkers for ASD diagnosis. Methods: The five parameters related to the serotonin-melatonin pathway, i.e. serotonin, arylalkylamine N-acetyltransferase (AA-NAT) enzyme activity, N-acetylserotonin, acetylserotonin methyltransferase (ASMT) enzyme activity, and melatonin, were measured in the blood of 203 patients with ASD, their unaffected relatives (291 parents and 92 sibs), and age- and sex-matched controls. Biochemical data were correlated with clinical data obtained from ADI-R for 117 patients. Results: Patients with ASD display elevated blood serotonin and N-acetylserotonin levels (p<0,001) compared to controls and unaffected relatives, and decreased ASMT activity and melatonin levels (p<0,001) compared to controls. When confronted to clinical data, melatonin deficiency appears significantly associated with stereotyped behavior (ADI-R axis D, p=0,003). Finally, comparisons between ASD patients, controls and unaffected sibs on the one hand, and between autism and Asperger syndrome on the other hand, reveal that hyperserotoninemia is a relevant biomarker of autism, with good specificity and sensitivity. Conclusions: This study confirms the previously reported major abnormalities of the serotonin-melatonin pathway in ASD. The typical biochemical profile of ASD patients suggests a deficit of the ASMT enzyme, consistent with our previous work. Serotonin and melatonin are both clinically relevant parameters, serotonin as a specific biomarker of autism, and melatonin for behavioral correlates. These results highlight the clinical interest of the serotonin –melatonin pathway in ASD, and its potential role as a susceptibility factor to autism.
    International Meeting for Autism Research 2010; 05/2010

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