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Eur J Paediatr Neurol. 2015 Mar;19(2):122-33. doi: 10.1016/j.ejpn.2014.12.007. Epub 2014 Dec 17.

Current role of melatonin in pediatric neurology: clinical recommendations.

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Department of Developmental and Social Psychology, Sapienza University, Rome, Italy.
Institute for Women's Health, University College London, London, UK; Department of Cell Biology and Histology, University of the Basque Country, Spain.
South Essex Partnership University NHS Foundation Trust, Bedfordshire, & Institute of Psychiatry, London, UK.
Neonatal Intensive Care Unit, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Univ Paris Diderot, 75019 Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, INSERM, U1141, 75019 Paris, France.
's Heeren Loo, Department Advisium, Wekerom, The Netherlands; Governor Kremers Centre, University Maastricht, The Netherlands.
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; School of Medicine, and the Centre for ADHD and Neurodevelopmental Disorders Across the Lifespan, Institute of Mental Health, University of Nottingham, UK; New York University Child Study Center, NY, USA.
Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University of Rome, Italy; Neurology Unit, Neuroscience Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Child Neurology-Chair of Pediatrics, c/o Sant'Andrea Hospital, NESMOS Department, Faculty of Medicine & Psychology, Sapienza University, Rome, Italy.
Governor Kremers Centre, University Maastricht, The Netherlands; Department of Sleep-wake Disorders and Chronobiology, Hospital Gelderse Vallei Ede, The Netherlands.
Leiden Institute for Brain and Cognition & Institute of Education and Child Studies, Leiden University, The Netherlands.
Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University of Rome, Italy. Electronic address:



Melatonin, an indoleamine secreted by the pineal gland, plays a key role in regulating circadian rhythm. It has chronobiotic, antioxidant, anti-inflammatory and free radical scavenging properties.


A conference in Rome in 2014 aimed to establish consensus on the roles of melatonin in children and on treatment guidelines.


The best evidence for efficacy is in sleep onset insomnia and delayed sleep phase syndrome. It is most effective when administered 3-5 h before physiological dim light melatonin onset. There is no evidence that extended-release melatonin confers advantage over immediate release. Many children with developmental disorders, such as autism spectrum disorder, attention-deficit/hyperactivity disorder and intellectual disability have sleep disturbance and can benefit from melatonin treatment. Melatonin decreases sleep onset latency and increases total sleep time but does not decrease night awakenings. Decreased CYP 1A2 activity, genetically determined or from concomitant medication, can slow metabolism, with loss of variation in melatonin level and loss of effect. Decreasing the dose can remedy this. Animal work and limited human data suggest that melatonin does not exacerbate seizures and might decrease them. Melatonin has been used successfully in treating headache. Animal work has confirmed a neuroprotective effect of melatonin, suggesting a role in minimising neuronal damage from birth asphyxia; results from human studies are awaited. Melatonin can also be of value in the performance of sleep EEGs and as sedation for brainstem auditory evoked potential assessments. No serious adverse effects of melatonin in humans have been identified.


ADHD; Autism; Epilepsy; Insomnia; Melatonin treatment; Sleep disorders

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