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


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.

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Available from: Diane Fawkes, Mar 26, 2014
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    • "Furthermore, there is a direct relationship between a reduction in the hours of night sleep and the severity of behavioral stereotypes, difficulties in social interactions, communication disorders and family stress (Richdale, 1999; Elia et al., 2000; Gregory and O'Connor, 2002; Thunström, 2002; O'Brien and Gozal, 2004; Hoffman et al., 2008; Miano and Ferri, 2010; Minkel et al., 2012). Because several studies have indicated that sleep quality influences aspects of behavior (Malow et al., 2006; Giannotti et al., 2008; Maski and Kothare, 2013) and that the treatment of sleep disturbances can improve daytime behavior, including less irritability, anxiety, withdrawal and hyperactivity; fewer affective problems, attention deficits, and stereotyped and compulsive behaviors; and better mood and communication, in children with ASD and in children who are neurologically multiply disabled (Jan et al., 1994; Horrigan and Barnhill, 1997; Ishizaki et al., 1999; Paavonen et al., 2003; Garstang and Wallis, 2006; Giannotti et al., 2006; De Leersnyder et al., 2011; Wright et al., 2011; Malow et al., 2012), the aim of this study was to investigate the patterns of sleep, behavioral profiles and the correlation between sleep disorders and behavior in children and adolescents with ASD. This study provided pilot data toward a new study, in which we intend to expand the sample, use pharmacological treatment to improve sleep quality in this population and investigate whether there was consequent improvement in behavioral and cognitive parameters. "
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    ABSTRACT: The aim of this study was to investigate the correlation between sleep disorders and the behavior of subjects with autism spectrum disorder (ASD) and control subjects using specific questionnaires. A small percentage (1.8%) of the control subjects had symptoms indicative of sleep-breathing disorders (SBD) and nocturnal sweating. Fifty-nine percent of the subjects with ASD had symptoms indicative of at least one sleep disorder, with SBD the most commonly reported (38%). In the control group, the symptoms of SBD were correlated with social, thought, attentional, aggression, externalizing and behavioral problems. In the ASD group, disorders of arousal (DA) were correlated with thinking problems, and disorders of excessive somnolence were correlated with thinking and behavioral problems. These results suggest that children and adolescents with ASD have a high frequency of sleep disorders, which in turn correlate with some of the behavioral traits that they already exhibit. Furthermore, sleep disturbances, when present in the typically developing children, also correlated with behavioral problems.
    Frontiers in Human Neuroscience 06/2015; 9:347. DOI:10.3389/fnhum.2015.00347 · 2.99 Impact Factor
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    • "Two DNA samples were extracted from buccal swabs, the remaining 13 DNA samples were extracted from patient blood, using QIagen Puregene Ò chemistry on the Autopure Ò platform at the Vanderbilt DNA Resources Core. Eleven of these 15 children were subsequently enrolled in the melatonin trial (Malow et al. 2012) and were initially started on liquid placebo for 2 weeks to obtain baseline data (Table 1). Individuals were then treated with 1 mg of supplemental liquid melatonin (Natrol Ò ) for 3 weeks. "
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    ABSTRACT: Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with comorbid expression of sleep onset delay. We evaluated variation in two melatonin pathway genes, acetylserotonin O-methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher frequencies than currently reported (p < 0.04) for variants evidenced to decrease ASMT expression and related to decreased CYP1A2 enzyme activity (p ≤ 0.0007). We detected a relationship between genotypes in ASMT and CYP1A2 (r(2) = 0.63). Our results indicate that expression of sleep onset delay relates to melatonin pathway genes.
    Journal of Autism and Developmental Disorders 07/2014; 45(1). DOI:10.1007/s10803-014-2197-4 · 3.34 Impact Factor
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    • "a 14-week treatment period, melatonin improved symptoms after 1 week of supplementation, and the beneficial effects were maintained over several months. Melatonin effectively alleviated sleep and behavioral problems, reduced parenting stress, and was safe and well tolerated by the subjects [12]. Although melatonin is presently unavailable in many countries, including Japan, ramelteon, a melatonin agonist, is used for the treatment of insomnia in the United States and Asia. "
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    ABSTRACT: Children with autism spectrum disorders (ASD), including autistic disorder, frequently suffer from comorbid sleep problems. An altered melatonin rhythm is considered to underlie the impairment in sleep onset and maintenance in ASD. We report three cases with autistic disorder in whom nocturnal symptoms improved with ramelteon, a selective melatonin receptor agonist. Insomnia and behavior, assessed using the Clinical Global Impression-Improvement Scale, improved in two cases with 2 mg ramelteon and in the third case with 8 mg ramelteon. Our findings demonstrate that ramelteon is effective not only for insomnia, but for behavioral problems as well, in patients with autistic disorder.
    05/2014; 2014:561071. DOI:10.1155/2014/561071
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