Abstract
Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.
Similar content being viewed by others
References
Aman MG, Lam KS, Collier-Crespin A (2003) Prevalence and patterns of use of psychoactive medicines among individuals with autism in the Autism Society of Ohio. J Autism Dev Disord 33(5):527–534
Andersen IM, Kaczmarska J, McGrew SG, Malow BA (2008) Melatonin for insomnia in children with autism spectrum disorders. J Child Neurol 23(5):482–485 (Epub 2008 Jan 8)
Beaumanoir-De PC, Mouraeff Y, Doyen C, Colineaux C, Rieu C, Paubel P, Contejean Y (2010) Use of melatonin for the sleep disturbances in children with ASD. Poster presented at the 8th Encéphale Congress
Bourgeron T (2007) The possible interplay of synaptic and clock genes in autism spectrum disorders. Cold Spring Harb Symp Quant Biol 72:645–654 (Review)
Chamberlain RS, Herman BH (1990) A novel biochemical model linking dysfunction in brain melatonin, proopiomelanocortin peptides, and serotonin in autism. Biol Psychiatry 28(9):773–793 (Review)
Chen F, Lemonnier E, Lazartigues A, Planche P (2006) Sleep problems and information processing, a “disconnection effect” in autism? Med Hypotheses 66(6):1245–1246 (Epub 2006 Feb 28)
De Groot Jameson (2006) Endocrinology, Edit. Elsevier Saunders, 2006, vol 1, 557–572
Galli-Carminati G, Deriaz N, Bertschy G (2009) Melatonin in treatment of chronic sleep disorders in adults with autism: a retrospective study. Swiss Med Wkly 139(19–20):293–296
Garstang J, Wallis M (2006) Randomized controlled trial of melatonin for the children with autistic spectrum disorders. Child Care Health Dev 32(5):585–589
Giannotti F, Cortesi F, Cerquiglini A, Bernabei P (2006) An open-label study of controlled release melatonin in treatment of sleep disorders in children with autism. J Autism Dev Disord 36(6):741–752
Golnik AE, Ireland M (2009) Complementary alternative medicine for children with autism: a physician survey. J Autism Dev Disord 39(7):996–1005
Guénolé F, Baleyte JM (2010) Effectiveness of melatonin for sleep problems in autism spectrum disorders: evidence grows but researches is still needed. J Autism Dev Disord (Epub ahead of print)
Gupta R, Hutchins J (2005) Melatonin: un panacea for desperate parents? (Hype or truth). Arch Dis Child 90(9):986–987
Hayashi E (2000) Effect of melatonin on sleep-wake rhythm: the sleep diary of an autistic male. Psychiatry Clin Neurosci 54(3):383–384
Henry HL, Norman AW (2003) Encyclopedia of hormones, vol 2. Academic Press, Amsterdam, pp 631–644
Horrigan JP, Barnhill LJ (1997) More on melatonin. J Am Acad Child Adolesc Psychiatry 36(8):1014
Ishizaki A, Sugama M, Takeuchi N (1999) Usefulness of melatonin for developmental sleep and emotional/behaviour disorders—studies of melatonin trial on 50 patients with developmental disorders. No To Hattatsu 31(5):487–537
Jan JE, Freeman RD, Wasdell MB, Bomben MM (2004) A child with severe night terrors and sleep-walking responds to melatonin therapy. Dev Med Child Neurol 46(11):789
Jan JE, O’Donnell ME (1996) Use of melatonin in the treatment of paediatric sleep disorders. J Pineal Res 21(4):193–199 (Review)
Johnson KP, Malow BA (2008) Assessment and pharmachologic treatment of sleep disturbance in autism. Chil Adolesc Psychiatr Clin N Am 17(4):773–785 (Review)
Kulman G, Lissoni P, Rovelli F, Roselli MG, Brivio F, Sequeri P (2000) Evidence of pineal endocrine hypofunction in autistic children. Neuro Endocrinol Lett 21(1):31–34
Leu RM, Beyderman L, Botzolakis EJ, Surdyka K, Wang L, Malow BA (2010) Relation of melatonin to sleep architecture in children with autism. J Autism Dev Disord (Epub ahead of print)
Levy SE, Hyman SL (2008) Complementary and alternative medicine treatments for children with autism spectrum disorders. Chil Adolesc Psychiatr Clin N Am 17(4):803–820 Review
Lord C (1998) What is melatonin? It is a useful treatment for sleep problems in autism? J Aut Dev Disord 28(4):345–346
Malow BA (2004) Sleep disorders, epilepsy and autism. Ment Retard Dev Disabil Res Rev 10(2):122–125 Review
Martini L (2003) Encyclopedia of endocrine disease, vol 3, Elsevier Academic Press, Milan, pp 228–237
McArthur AJ, Budden SS (1998) Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol 40(3):186–192
Melke J, Goubran Botros H, Chaste P et al (2008) Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry 13(1):90–98 (Epub 2007 May)
Miyamoto A, Oki J, Takahashi S, Okuno A (1999) Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome. Brain Dev 21(1):59–62
Nir I, Meir D, Zilber N, Knobler H (1995) Brief report: circadian melatonin, thyroid-stimulating hormone, prolactine, cortisol levels in serum of young adults with autism. J Autism Dev Disord 25(6):641–654
Owens JA, Rosen CL, Mindell JA (2003) Medication use in the treatment of pediatric insomnia: results of a survey of community-based pediatricians. Pediatrics 111(5Pt 1):e628–e635
Paavonen EJ, Nieminen-von Wendt T, Vanhala R, Aronen ET, von Wendt L (2003) Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. J Child Adolesc Psychopharmacol 13(1):83–95
Pandi-Perumal SR, Srinivasan V, Spence DW, Cardinali DP (2007) Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs 21(12):995–1018 (Review)
Patzold LM, Richdale AL, Tonge BJ (1998) An investigation into the sleep characteristics of children with autism and Asperger’s disorder. J Paediatr Child Health 34(6):528–533
Reiter RJ, Tan DX, Manchester C, Pilar Terron M, Flores LJ, Koppiespi S (2007) Medical implcations of melatonin receptor-mediated and receptor-independent actions. Adv Med Sci 52:11–28
Rossignol DA (2009) Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann Clin Psychiatry 21(4):213–236
Rufo-Campos M (2002) Melatonin and epilepsy. Rev Neurol 35(Suppl 1):S51–S58 (Review)
Tordjman S, Anderson GM, Pichard N, Charbury H, Touitou Y (2005) Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biol Psychiatry 57(2):134–138
Wasdell MB, Jan JE, Bomben MM, Freeman RD (2008) A randomized, placebo controlled trial of controlled release melatonin treatment of delayed sleep phase, impaired sleep maintenance in children with neurodevelopmental disabilities. J Pineal Res 44(1):57–64
Wirojanan J, Jacquemont S, Diaz R, Bacalman S, Anders TF, Hagerman RJ, Goodlin-Jones BI (2009) The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. J Clin Sleep Med 5(2):145–150
Wright B, Sims D, Smart S, Alwazeer A, Alderson-Day B, Allgar V, Whitton C, Tomlinson H, Bennett S, Jardine J et al (2011) Melatonin versus placebo in children with autistism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial. J Autism Dev Disord 41(2):175–184
Yamashita Y, Matsuishi T, Murakami Y, Kato H (1999) Sleep disorder in Rett syndrome and melatoni treatment. Brain Dev 21(8):570
Yun AJ, Bazar KA, Lee PY (2004) Pineal attrition, loss of cognitive plasticity, and onset puberty during the ten years: it is a modern maladaptation exposed by evolutionary displacement? Med Hypotheses 63(6):939–950
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Doyen, C., Mighiu, D., Kaye, K. et al. Melatonin in children with autistic spectrum disorders: recent and practical data. Eur Child Adolesc Psychiatry 20, 231–239 (2011). https://doi.org/10.1007/s00787-011-0162-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00787-011-0162-8