Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: A randomized placebo-controlled trial

Department of Pediatrics and Developmental Neuropsychiatry, Center of Pediatric Sleep Disorders, University of Rome 'La Sapienza', Italy.
Journal of Sleep Research (Impact Factor: 3.35). 05/2012; 21(6). DOI: 10.1111/j.1365-2869.2012.01021.x
Source: PubMed


Although melatonin and cognitive-behavioural therapy have shown efficacy in treating sleep disorders in children with autism spectrum disorders, little is known about their relative or combined efficacy. One hundred and sixty children with autism spectrum disorders, aged 4-10 years, suffering from sleep onset insomnia and impaired sleep maintenance, were assigned randomly to either (1) combination of controlled-release melatonin and cognitive-behavioural therapy; (2) controlled-release melatonin; (3) four sessions of cognitive-behavioural therapy; or (4) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1 ratio. Children were studied at baseline and after 12 weeks of treatment. Treatment response was assessed with 1-week actigraphic monitoring, sleep diary and sleep questionnaire. Main outcome measures, derived actigraphically, were sleep latency, total sleep time, wake after sleep onset and number of awakenings. The active treatment groups all resulted in improvements across all outcome measures, with moderate-to-large effect sizes from baseline to a 12-week assessment. Melatonin treatment was mainly effective in reducing insomnia symptoms, while cognitive-behavioural therapy had a light positive impact mainly on sleep latency, suggesting that some behavioural aspects might play a role in determining initial insomnia. The combination treatment group showed a trend to outperform other active treatment groups, with fewer dropouts and a greater proportion of treatment responders achieving clinically significant changes (63.38% normative sleep efficiency criterion of >85% and 84.62%, sleep onset latency <30 min). This study demonstrates that adding behavioural intervention to melatonin treatment seems to result in a better treatment response, at least in the short term.

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Available from: Flavia Cortesi, Oct 13, 2014
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    • "Although melatonin has a variety of physiological effects apart from altering sleep timing and unproven safety assurance for long term use in paediatrics[8], it has less overt adverse effects compared to other sleep-inducing drugs[6,9,10]. Most of the studies examining the effects of melatonin in children and adolescents report the use in medical conditions such as autism spectrum disorders111213141516, attention deficit hyperactivity disorders171819, and other neurodevelopmental disorders202122. In 2008, it was estimated that 5000 children in the UK with sleep disorders were being treated with melatonin[23]. "
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    ABSTRACT: Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.
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    • "Regarding the possible causes, there is a hypothesis that children who are more sensitive to external stimuli can become more vigilant and hyperactive and have some resistance at bedtime, increasing insomnia rates in this population (Hollway and Aman, 2011). Furthermore, this rhythm is known to be modulated by the neurohormone melatonin, the nocturnal production of which is decreased in autism and which is good a candidate for sleep treatment (Cortesi et al., 2012; Tordjman et al., 2015) Regarding the sleep characteristics, subjective data about sleep patterns, such as questionnaires completed by the parents and sleep diaries, as well as objective data (polysomnography and actigraphy) indicate that the most striking feature of sleep in individuals with ASD is the inability to maintain the required latency time; common complaints include difficulty initiating and/or maintaining sleep, reduced total sleep, waking during the night and in the early morning and being unable to stay awake during the day (Elia et al., 2000; Schreck and Mulick, 2000; Miano and Ferri, 2010). As a consequence, the sleep–wake rhythm associated with biological circadian rhythms can be viewed as an adaptation to the day–night cycle, which seems to be important for the rhythmicity and synchrony of motor, emotional, and relational rhythms during the early development of social communication (Tordjman et al., 2015). "
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    Full-text · Article · Jun 2015 · Frontiers in Human Neuroscience
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    • "In addition, a randomized placebo-controlled trial examining insomnia in children with ASD was conducted. In their study, they compared melatonin alone, melatonin combined with cognitive behavioral therapy, cognitive-behavioral therapy and placebo in children with ASD.90 Findings suggested that adding behavioral intervention to melatonin treatment, resulted in better treatment response, at least in the short term. "
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    ABSTRACT: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with both core symptoms and associated symptoms (eg, irritability, aggression, and comorbidities) that affect both the individual and the family/systems around them. There have been recent advances in the understanding of the underlying pathophysiology of ASD pertaining to genetics, epigenetics, neurological, hormonal, and environmental factors that contribute to the difficulties found in individuals with ASD. With this improved understanding, there has been a shift in the application of psychopharmacology in ASD and its related disorders. A literature review was conducted to examine research published in the last 5 years between different classes of psychotropic medications and ASD. The broad scope of the existing literature for the use of conventional medications is summarized and novel medications are discussed.
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