Current role of melatonin in pediatric neurology: Clinical recommendations

Published:December 17, 2014DOI:https://doi.org/10.1016/j.ejpn.2014.12.007

      Abstract

      Background/purpose

      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.

      Methods

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

      Results and Conclusion

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Paediatric Neurology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gordon N.
        The therapeutics of melatonin: a paediatric perspective.
        Brain Dev. 2000; 22: 213-217
        • Kennaway D.J.
        Melatonin and development: physiology and pharmacology.
        Semin Perinatol. 2000; 24: 258-266
        • Mauriz J.L.
        • Collado P.S.
        • Veneroso C.
        • Reiter R.J.
        • Gonzalez-Gallego J.
        A review of the molecular aspects of melatonin's anti-inflammatory actions: recent insights and new perspectives.
        J Pineal Res. 2013; 54: 1-14
        • Niles L.P.
        • Armstrong K.J.
        • Rincon Castro L.M.
        • et al.
        Neural stem cells express melatonin receptors and neurotrophic factors: colocalization of the MT1 receptor with neuronal and glial markers.
        BMC Neurosci. 2004; 5: 41
        • Iwasaki S.
        • Nakazawa K.
        • Sakai J.
        • et al.
        Melatonin as a local regulator of human placental function.
        J Pineal Res. 2005; 39: 261-265
        • Comai S.
        • Ochoa-Sanchez R.
        • Gobbi G.
        Sleep–wake characterization of double MT(1)/MT(2) receptor knockout mice and comparison with MT(1) and MT(2) receptor knockout mice.
        Behav Brain Res. 2013; 243: 231-238
        • Wirz-Justice A.
        • Armstrong S.M.
        Melatonin: nature's soporific?.
        J Sleep Res. 1996; 5: 137-141
        • Nagtegaal J.E.
        • Kerkhof G.A.
        • Smits M.G.
        • Swart A.C.
        • Van Der Meer Y.G.
        Delayed sleep phase syndrome: a placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset.
        J Sleep Res. 1998; 7: 135-143
        • van Geijlswijk I.M.
        • Korzilius H.P.
        • Smits M.G.
        The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis.
        Sleep. 2010; 33: 1605-1614
        • van Geijlswijk I.M.
        • van der Heijden K.B.
        • Egberts A.C.
        • Korzilius H.P.
        • Smits M.G.
        Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT.
        Psychopharmacology. 2010; 212: 379-391
        • Braam W.
        • van Geijlswijk I.
        • Keijzer H.
        • et al.
        Loss of response to melatonin treatment is associated with slow melatonin metabolism.
        J Intellect Disabil Res. 2010; 54: 547-555
        • Appleton R.E.
        • Gringras P.
        Melatonin: helping to MEND impaired sleep.
        Arch Dis Child. 2013; 98: 216-217
        • Owens J.A.
        • Rosen C.L.
        • Mindell J.A.
        Medication use in the treatment of pediatric insomnia: results of a survey of community-based pediatricians.
        Pediatrics. 2003; 111: e628-e635
        • Owens J.A.
        Pharmacotherapy of pediatric insomnia.
        J Am Acad Child Adolesc Psychiatry. 2009; 48: 99-107
        • Owens J.A.
        • Rosen C.L.
        • Mindell J.A.
        • Kirchner H.L.
        Use of pharmacotherapy for insomnia in child psychiatry practice: a national survey.
        Sleep Med. 2010; 11: 692-700
        • Hartz I.
        • Furu K.
        • Bratlid T.
        • Handal M.
        • Skurtveit S.
        Hypnotic drug use among 0–17 year olds during 2004–2011: a nationwide prescription database study.
        Scand J public health. 2012; 40: 704-711
        • Heussler H.
        • Chan P.
        • Price A.M.
        • et al.
        Pharmacological and non-pharmacological management of sleep disturbance in children: an Australian paediatric research network survey.
        Sleep Med. 2013; 14: 189-194
        • Merchant N.M.
        • Azzopardi D.V.
        • Hawwa A.F.
        • et al.
        Pharmacokinetics of melatonin in preterm infants.
        Br J Clin Pharmacol. 2013; 76: 725-733
        • Sadeh A.
        Sleep and melatonin in infants: a preliminary study.
        Sleep. 1997; 20: 185-191
        • LeBourgeois M.K.
        • Carskadon M.A.
        • Akacem L.D.
        • et al.
        Circadian phase and its relationship to nighttime sleep in toddlers.
        J Biol Rhythms. 2013; 28: 322-331
        • Shinohara H.
        • Kodama H.
        Relationship between circadian salivary melatonin levels and sleep–wake behavior in infants.
        Pediatr Int off J Jpn Pediatr Soc. 2011; 53: 29-35
        • Tauman R.
        • Zisapel N.
        • Laudon M.
        • Nehama H.
        • Sivan Y.
        Melatonin production in infants.
        Pediatr Neurol. 2002; 26: 379-382
        • Hartmann L.
        • Roger M.
        • Lemaitre B.J.
        • Massias J.F.
        • Chaussain J.L.
        Plasma and urinary melatonin in male infants during the first 12 months of life.
        Clin Chimica Acta Int J Clin Chem. 1982; 121: 37-42
        • Attanasio A.
        • Rager K.
        • Gupta D.
        Ontogeny of circadian rhythmicity for melatonin, serotonin, and N-acetylserotonin in humans.
        J Pineal Res. 1986; 3: 251-256
        • Waldhauser F.
        • Weiszenbacher G.
        • Frisch H.
        • et al.
        Fall in nocturnal serum melatonin during prepuberty and pubescence.
        Lancet. 1984; 1: 362-365
        • Griefahn B.
        • Brode P.
        • Blaszkewicz M.
        • Remer T.
        Melatonin production during childhood and adolescence: a longitudinal study on the excretion of urinary 6-hydroxymelatonin sulfate.
        J Pineal Res. 2003; 34: 26-31
        • Smits M.G.
        • van Stel H.F.
        • van der Heijden K.
        • et al.
        Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial.
        J Am Acad Child Adolesc Psychiatry. 2003; 42: 1286-1293
        • van Maanen A.
        • Meijer A.M.
        • Smits M.G.
        • Oort F.J.
        Termination of short term melatonin treatment in children with delayed dim light melatonin onset: effects on sleep, health, behavior problems, and parenting stress.
        Sleep Med. 2011; 12: 875-879
        • Hoebert M.
        • van der Heijden K.B.
        • van Geijlswijk I.M.
        • Smits M.G.
        Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia.
        J Pineal Res. 2009; 47: 1-7
        • van Geijlswijk I.M.
        • Mol R.H.
        • Egberts T.C.
        • Smits M.G.
        Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomnia.
        Psychopharmacology. 2011; 216: 111-120
        • Burgess H.J.
        • Revell V.L.
        • Molina T.A.
        • Eastman C.I.
        Human phase response curves to three days of daily melatonin: 0.5 mg versus 3.0 mg.
        J Clin Endocrinol Metab. 2010; 95: 3325-3331
        • EFSA
        Panel on dietetic products NaAN. Scientific opinion on the substantiation of health claims related to melatonin and alleviation of subjective feelings of jet lag (ID 1953), and reduction of sleep onset latency, and improvement of sleep quality (ID 1953) pursuant to Article 13(1) of Regulation (EC) No 1924/2006.
        EFSA J. 2010; 8: 1467
        • EFSA
        Panel on dietetic products NaAN. Scientific Opinion on the substantiation of a health claim related to melatonin and reduction of sleep onset latency (ID 1698, 1780, 4080) pursuant to article 13(1) of regulation (EC) no 1924/2006.
        EFSA J. 2011; 9: 2241
        • van der Heijden K.B.
        • Smits M.G.
        • van Someren E.J.
        • Boudewijn Gunning W.
        Prediction of melatonin efficacy by pretreatment dim light melatonin onset in children with idiopathic chronic sleep onset insomnia.
        J Sleep Res. 2005; 14: 187-194
        • Keijzer H.
        • Smits M.G.
        • Peeters T.
        • et al.
        Evaluation of salivary melatonin measurements for dim light melatonin onset calculations in patients with possible sleep–wake rhythm disorders.
        Clin Chimica Acta Int J Clin Chem. 2011; 412: 1616-1620
        • Keijzer H.
        • Smits M.G.
        • Duffy J.F.
        • Curfs L.M.
        Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders.
        Sleep Med Rev. 2014; 18: 333-339
        • Shibui K.
        • Uchiyama M.
        • Okawa M.
        Melatonin rhythms in delayed sleep phase syndrome.
        J Biol Rhythms. 1999; 14: 72-76
        • Ebisawa T.
        • Uchiyama M.
        • Kajimura N.
        • et al.
        Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome.
        EMBO Rep. 2001; 2: 342-346
        • Archer S.N.
        • Robilliard D.L.
        • Skene D.J.
        • et al.
        A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference.
        Sleep. 2003; 26: 413-415
        • Gradisar M.
        • Crowley S.J.
        Delayed sleep phase disorder in youth.
        Curr Opin Psychiatry. 2013; 26: 580-585
        • Micic G.
        • de Bruyn A.
        • Lovato N.
        • et al.
        The endogenous circadian temperature period length (tau) in delayed sleep phase disorder compared to good sleepers.
        J Sleep Res. 2013; 22: 617-624
        • Buscemi N.
        • Vandermeer B.
        • Hooton N.
        • et al.
        The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis.
        J Gen Intern Med. 2005; 20: 1151-1158
        • Ferracioli-Oda E.
        • Qawasmi A.
        • Bloch M.H.
        Meta-analysis: melatonin for the treatment of primary sleep disorders.
        PLoS One. 2013; 8: e63773
        • Smits M.G.
        • Nagtegaal E.E.
        • van der Heijden J.
        • Coenen A.M.
        • Kerkhof G.A.
        Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial.
        J Child Neurol. 2001; 16: 86-92
        • Eckerberg B.
        • Lowden A.
        • Nagai R.
        • Akerstedt T.
        Melatonin treatment effects on adolescent students' sleep timing and sleepiness in a placebo-controlled crossover study.
        Chronobiol Int. 2012; 29: 1239-1248
        • Wilhelmsen-Langeland A.
        • Saxvig I.W.
        • Pallesen S.
        • et al.
        A randomized controlled trial with bright light and melatonin for the treatment of delayed sleep phase disorder: effects on subjective and objective sleepiness and cognitive function.
        J Biological Rhythms. 2013; 28: 306-321
        • Saxvig I.W.
        • Wilhelmsen-Langeland A.
        • Pallesen S.
        • et al.
        A randomized controlled trial with bright light and melatonin for delayed sleep phase disorder: effects on subjective and objective sleep.
        Chronobiol Int. 2014; 31: 72-86
        • Braam W.
        • Smits M.G.
        • Didden R.
        • et al.
        Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis.
        Dev Med Child Neurol. 2009; 51: 340-349
        • Buscemi N.
        • Vandermeer B.
        • Hooton N.
        • et al.
        Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis.
        BMJ. 2006; 332: 385-393
        • Cortese S.
        • Faraone S.V.
        • Konofal E.
        • Lecendreux M.
        Sleep in children with attention-deficit/hyperactivity disorder: meta-analysis of subjective and objective studies.
        J Am Acad Child Adolesc Psychiatry. 2009; 48: 894-908
        • Cortese S.
        • Lecendreux M.
        • Mouren M.C.
        • Konofal E.
        ADHD and insomnia.
        J Am Acad Child Adolesc Psychiatry. 2006; 45: 384-385
        • Kirov R.
        • Brand S.
        Sleep problems and their effect in ADHD.
        Expert Rev Neurother. 2014; 14: 287-299
        • Cortese S.
        • Brown T.E.
        • Corkum P.
        • et al.
        Assessment and management of sleep problems in youths with attention-deficit/hyperactivity disorder.
        J Am Acad Child Adolesc Psychiatry. 2013; 52: 784-796
        • Van der Heijden K.B.
        • Smits M.G.
        • Van Someren E.J.
        • Gunning W.B.
        Idiopathic chronic sleep onset insomnia in attention-deficit/hyperactivity disorder: a circadian rhythm sleep disorder.
        Chronobiol Int. 2005; 22: 559-570
        • Chaste P.
        • Clement N.
        • Botros H.G.
        • et al.
        Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.
        J Pineal Res. 2011; 51: 394-399
      1. Interventions CHfSRo. Cochrane Handbook for systematic reviews of interventions, Version 5.1.0 [updated March 2011]. In: Higgins JPT GS editor.

        • Owens J.
        • Gruber R.
        • Brown T.
        • et al.
        Future research directions in sleep and ADHD: report of a consensus working group.
        J Atten Disord. 2013; 17: 550-564
        • Tjon Pian Gi C.V.
        • Broeren J.P.
        • Starreveld J.S.
        • Versteegh F.G.
        Melatonin for treatment of sleeping disorders in children with attention deficit/hyperactivity disorder: a preliminary open label study.
        Eur J Pediatr. 2003; 162: 554-555
        • Weiss M.D.
        • Wasdell M.B.
        • Bomben M.M.
        • Rea K.J.
        • Freeman R.D.
        Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia.
        J Am Acad Child Adolesc Psychiatry. 2006; 45: 512-519
        • Van der Heijden K.B.
        • Smits M.G.
        • Van Someren E.J.
        • Ridderinkhof K.R.
        • Gunning W.B.
        Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 233-241
        • Mohammadi M.R.
        • Mostafavi S.A.
        • Keshavarz S.A.
        • et al.
        Melatonin effects in methylphenidate treated children with attention deficit hyperactivity disorder: a randomized double blind clinical trial.
        Iran J psychiatry. 2012; 7: 87-92
        • Krakowiak P.
        • Goodlin-Jones B.
        • Hertz-Picciotto I.
        • Croen L.A.
        • Hansen R.L.
        Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study.
        J Sleep Res. 2008; 17: 197-206
        • Sivertsen B.
        • Posserud M.B.
        • Gillberg C.
        • Lundervold A.J.
        • Hysing M.
        Sleep problems in children with autism spectrum problems: a longitudinal population-based study.
        Autism Int J Res Pract. 2012; 16: 139-150
        • Tordjman S.
        • Anderson G.M.
        • Pichard N.
        • Charbuy H.
        • Touitou Y.
        Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder.
        Biol Psychiatry. 2005; 57: 134-138
        • Goldman S.E.
        • Adkins K.W.
        • Calcutt M.W.
        • et al.
        Melatonin in children with autism spectrum disorders: endogenous and pharmacokinetic profiles in relation to sleep.
        J Autism Dev Disord. 2014; 44: 2525-2535
        • Veatch O.J.
        • Pendergast J.S.
        • Allen M.J.
        • et al.
        Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay.
        J Autism Dev Disord. 2014; (ePub ahead of print)
        • Rossignol D.A.
        • Frye R.E.
        Melatonin in autism spectrum disorders: a systematic review and meta-analysis.
        Dev Med Child Neurol. 2011; 53: 783-792
        • Braam W.
        • Keijzer H.
        • Struijker Boudier H.
        • et al.
        CYP1A2 polymorphisms in slow melatonin metabolisers: a possible relationship with autism spectrum disorder?.
        J Intellect Disabil Res. 2013; 57: 993-1000
        • Tordjman S.
        • Najjar I.
        • Bellissant E.
        • et al.
        Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives.
        Int J Mol Sci. 2013; 14: 2050 8-205042
        • Harrington R.A.
        • Lee L.C.
        • Crum R.M.
        • Zimmerman A.W.
        • Hertz-Picciotto I.
        Serotonin hypothesis of autism: implications for selective serotonin reuptake inhibitor use during pregnancy.
        Autism Res off J Int Soc Autism Res. 2013; 6: 149-168
        • Daly E.
        • Ecker C.
        • Hallahan B.
        • et al.
        Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.
        Brain. 2014; 137: 2600-2610
        • Sajith S.G.
        • Clarke D.
        Melatonin and sleep disorders associated with intellectual disability: a clinical review.
        J Intellect Disabil Res. 2007; 51: 2-13
        • Gringras P.
        • Gamble C.
        • Jones A.P.
        • et al.
        Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial.
        BMJ. 2012; 345: e6664
        • Hartter S.
        • Ursing C.
        • Morita S.
        • et al.
        Orally given melatonin may serve as a probe drug for cytochrome P450 1A2 activity in vivo: a pilot study.
        Clin Pharmacol Ther. 2001; 70: 10-16
        • De Leersnyder H.
        Inverted rhythm of melatonin secretion in Smith-Magenis syndrome: from symptoms to treatment.
        Trends Endocrinol Metab TEM. 2006; 17: 291-298
        • Chik C.L.
        • Rollag M.D.
        • Duncan W.C.
        • Smith A.C.
        Diagnostic utility of daytime salivary melatonin levels in Smith-Magenis syndrome.
        Am J Med Genet A. 2010; 152A: 96-101
        • Braam W.
        • Didden R.
        • Smits M.G.
        • Curfs L.M.
        Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial.
        J Child Neurol. 2008; 23: 649-654
        • Bruni O.
        • Cortesi F.
        • Giannotti F.
        • Curatolo P.
        Sleep disorders in tuberous sclerosis: a polysomnographic study.
        Brain Dev. 1995; 17: 52-56
        • O'Callaghan F.J.
        • Clarke A.A.
        • Hancock E.
        • Hunt A.
        • Osborne J.P.
        Use of melatonin to treat sleep disorders in tuberous sclerosis.
        Dev Med Child Neurol. 1999; 41: 123-126
        • Hancock E.
        • O'Callaghan F.
        • Osborne J.P.
        Effect of melatonin dosage on sleep disorder in tuberous sclerosis complex.
        J Child Neurol. 2005; 20: 78-80
        • McArthur A.J.
        • Budden S.S.
        Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment.
        Dev Med Child Neurol. 1998; 40: 186-192
        • De Leersnyder H.
        • Zisapel N.
        • Laudon M.
        Prolonged-release melatonin for children with neurodevelopmental disorders.
        Pediatr Neurol. 2011; 45: 23-26
        • Fraser J.
        • Wraith J.E.
        • Delatycki M.B.
        Sleep disturbance in mucopolysaccharidosis type III (Sanfilippo syndrome): a survey of managing clinicians.
        Clin Genet. 2002; 62: 418-421
        • Fraser J.
        • Gason A.A.
        • Wraith J.E.
        • Delatycki M.B.
        Sleep disturbance in Sanfilippo syndrome: a parental questionnaire study.
        Arch Dis Child. 2005; 90: 1239-1242
        • Woolfenden S.
        • Sarkozy V.
        • Ridley G.
        • Coory M.
        • Williams K.
        A systematic review of two outcomes in autism spectrum disorder – epilepsy and mortality.
        Dev Med Child Neurol. 2012; 54: 306-312
        • Goldberg-Stern H.
        • Oren H.
        • Peled N.
        • Garty B.Z.
        Effect of melatonin on seizure frequency in intractable epilepsy: a pilot study.
        J Child Neurol. 2012; 27: 1524-1528
        • Brigo F.
        • Del Felice A.
        Melatonin as add-on treatment for epilepsy.
        Cochrane Database Syst Rev. 2012; 6: CD006967
        • Jain S.
        • Besag F.M.
        Does melatonin affect epileptic seizures? Drug safety.
        Int J Med Toxicol drug Exp. 2013; 36: 207-215
        • Srinivasan V.
        • Pandi-Perumal S.R.
        • Spence D.W.
        • et al.
        Potential use of melatonergic drugs in analgesia: mechanisms of action.
        Brain Res Bull. 2010; 81: 362-371
        • Reiter R.J.
        • Tan D.X.
        • Galano A.
        Melatonin: exceeding expectations.
        Physiology. 2014; 29: 325-333
        • Wilhelmsen M.
        • Amirian I.
        • Reiter R.J.
        • Rosenberg J.
        • Gogenur I.
        Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies.
        J Pineal Res. 2011; 51: 270-277
        • Nagtegaal J.E.
        • Smits M.G.
        • Swart A.C.
        • Kerkhof G.A.
        • van der Meer Y.G.
        Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations.
        Headache. 1998; 38: 303-307
        • Bruni O.
        • Galli F.
        • Guidetti V.
        Sleep hygiene and migraine in children and adolescents. Cephalalgia.
        Int J headache. 1999; 19: 57-59
        • Rovers J.
        • Smits M.
        • Duffy J.F.
        Headache and sleep: also assess circadian rhythm sleep disorders.
        Headache. 2014; 54: 175-177
        • Guidetti V.
        • Dosi C.
        • Bruni O.
        The relationship between sleep and headache in children: implications for treatment.
        Cephalalgia Int J headache. 2014; 34: 767-776
        • Miano S.
        • Parisi P.
        • Pelliccia A.
        • et al.
        Melatonin to prevent migraine or tension-type headache in children.
        Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2008; 29: 285-287
        • Fallah R.
        • Shoroki F.F.
        • Ferdosian F.
        Safety and efficacy of melatonin in pediatric migraine prophylaxis.
        Curr drug Saf. 2014; (ePub ahead of print)
        • Lee A.C.
        • Kozuki N.
        • Blencowe H.
        • et al.
        Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990.
        Pediatr Res. 2013; 74: 50-72
        • Alonso-Alconada D.
        • Alvarez A.
        • Arteaga O.
        • Martinez-Ibarguen A.
        • Hilario E.
        Neuroprotective effect of melatonin: a novel therapy against perinatal hypoxia-ischemia.
        Int J Mol Sci. 2013; 14: 9379-9395
        • Carloni S.
        • Perrone S.
        • Buonocore G.
        • et al.
        Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats.
        J Pineal Res. 2008; 44: 157-164
        • Alonso-Alconada D.
        • Alvarez A.
        • Lacalle J.
        • Hilario E.
        Histological study of the protective effect of melatonin on neural cells after neonatal hypoxia-ischemia.
        Histol Histopathol. 2012; 27: 771-783
        • Robertson N.J.
        • Faulkner S.
        • Fleiss B.
        • et al.
        Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model.
        Brain. 2013; 136: 90-105
        • Biran V.
        • Phan Duy A.
        • Decobert F.
        • et al.
        Is melatonin ready to be used in preterm infants as a neuroprotectant?.
        Dev Med Child Neurol. 2014; 56: 717-723
        • Ramanantsoa N.
        • Fleiss B.
        • Bouslama M.
        • et al.
        Bench to cribside: the path for developing a neuroprotectant.
        Transl stroke Res. 2013; 4: 258-277
        • Eisermann M.
        • Kaminska A.
        • Berdougo B.
        • Brunet M.L.
        Melatonin: experience in its use for recording sleep EEG in children and review of the literature.
        Neuropediatrics. 2010; 41: 163-166
        • Ashrafi M.R.
        • Mohammadi M.
        • Tafarroji J.
        • et al.
        Melatonin versus chloral hydrate for recording sleep EEG.
        Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. 2010; 14: 235-238
        • Wassmer E.
        • Carter P.F.
        • Quinn E.
        • et al.
        Melatonin is useful for recording sleep EEGs: a prospective audit of outcome.
        Dev Med Child Neurol. 2001; 43: 735-738
        • Sander J.
        • Shamdeen M.G.
        • Gottschling S.
        • et al.
        Melatonin does not influence sleep deprivation electroencephalogram recordings in children.
        Eur J Pediatr. 2012; 171: 675-679
        • Espezel H.
        • Graves C.
        • Jan J.E.
        • et al.
        Melatonin as a sedation substitute for diagnostic procedures.
        Dev Med Child Neurol. 2000; 42: 646-647
        • Schmidt C.M.
        • Bohlender J.E.
        • Deuster D.
        • et al.
        The use of melatonin as an alternative to sedation in children undergoing brainstem audiometry.
        Laryngo- Rhino- otologie. 2004; 83: 523-528
        • Wassmer E.
        • Fogarty M.
        • Page A.
        • et al.
        Melatonin as a sedation substitute for diagnostic procedures: MRI and EEG.
        Dev Med Child Neurol. 2001; 43: 136
        • Johnson K.
        • Page A.
        • Williams H.
        • Wassemer E.
        • Whitehouse W.
        The use of melatonin as an alternative to sedation in uncooperative children undergoing an MRI examination.
        Clin Radiol. 2002; 57: 502-506
        • Andersen I.M.
        • Kaczmarska J.
        • McGrew S.G.
        • Malow B.A.
        Melatonin for insomnia in children with autism spectrum disorders.
        J Child Neurol. 2008; 23: 482-485
        • Wasdell M.B.
        • Jan J.E.
        • Bomben M.M.
        • et al.
        A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities.
        J Pineal Res. 2008; 44: 57-64
        • Nagtegaal J.E.
        • Smits M.
        • Van Der Meer Y.G.
        • Fischer-Steenvoorden M.G.
        Melatonin: a survey of suspected adverse drug reactions.
        Sleep–Wake Res Netherl. 1996; 7: 115-118
        • Zhdanova I.V.
        • Wurtman R.J.
        • Regan M.M.
        • et al.
        Melatonin treatment for age-related insomnia.
        J Clin Endocrinol Metab. 2001; 86: 4727-4730
        • Srinivasan V.
        • Spence W.D.
        • Pandi-Perumal S.R.
        • et al.
        Melatonin and human reproduction: shedding light on the darkness hormone.
        Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2009; 25: 779-785
        • Carrillo-Vico A.
        • Reiter R.J.
        • Lardone P.J.
        • et al.
        The modulatory role of melatonin on immune responsiveness.
        Curr Opin Investig Drugs. 2006; 7: 423-431
        • Malow B.
        • Adkins K.W.
        • McGrew S.G.
        • et al.
        Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes.
        J Autism Dev Disord. 2012; 42 (author reply 38): 1729-1737
        • Damiani J.M.
        • Sweet B.V.
        • Sohoni P.
        Melatonin: an option for managing sleep disorders in children with autism spectrum disorder.
        Am J Health-Syst Pharm AJHP Off J Am Soc Health-Sys Pharm. 2014; 71: 95-101
        • Ray C.A.
        Melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans.
        J Physiol. 2003; 551: 1043-1048

      Linked Article

      • Paediatric use of melatonin
        European Journal of Paediatric NeurologyVol. 19Issue 4
        • Preview
          A recent review in the European Journal of Paediatric Neurology by Bruni et al.,1 discussed the current role of melatonin in paediatric neurology and offered clinical recommendations. The authors wrote in the abstract that melatonin decreases sleep onset latency and increases total sleep time. Furthermore they wrote that no serious adverse effects of melatonin in humans have been identified.
        • Full-Text
        • PDF