Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant differences between sleep variables at baseline. Melatonin significantly improved sleep latency (by an average of 47 min) and total sleep (by an average of 52 min) compared to placebo, but not number of night wakenings. The side effect profile was low and not significantly different between the two arms.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Allik, H., Larson, J. O., & Smedje, H. (2006). Sleep patterns of school age children with asperger syndrome or high functioning autism. Journal of Autism and Developmental Disorders, 36, 585–595.
Andersen, I. M., Kaczmarska, J., McGrew, S. G., & Malow, B. A. (2008). Melatonin for insomnia in children with autism spectrum disorders. Journal of Child Neurology, 23(5), 482–485.
Armour, D., & Paton, C. (2004). Melatonin in the treatment of insomnia in children and adolescents. Psychiatric Bulletin, 28, 222–224.
Bramble, D., & Feehan, C. (2005). Psychiatrists’ use of melatonin with children. Child and Adolescent Mental Health, 10(3), 145–149.
Buscemi, N., Vandermeer, B., Hooton, N., Pandya, R., Tjosvold, L., Hartling, L., et al. (2006). Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. British Medical Journal, 332, 385–388.
Camfield, P., Gordon, K., & Dooley, J. (1996). Melatonin appears ineffective in children with intellectual deficits and fragmented sleep: six ‘N of 1’ trials. Journal of Child Neurology, 11, 341–343.
Coppola, G., Iervolino, G., Mastrosimone, M., La Torre, G., Ruiu, F., & Pascotto, A. (2004). Melatonin in wake sleep disorders in children, adolescents and young adults with mental retardation with and without epilepsy: A double blind, cross over placebo controlled trial. Brain Development, 26(6), 373–376.
Council Directive (EC) 2001/20/EC of the European parliament and of the council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.
DeMuro, R. L., Nafziger, A. N., Blask, D. E., Menhinick, A. M., & Bertino, J. S. (2000). The absolute bioavailability of oral melatonin. The Journal of Clinical Pharmacology, 40, 781–784.
Dickerson Mayes, S., & Calhoun, S. L. (2009). Variables related to sleep problems in children with autism. Research in Autism Spectrum Disorders, 3(4), 931–941.
Dodge, N. N., & Wilson, G. A. (2001). Melatonin for treatment of sleep disorders in children with developmental disabilities. Journal of Child Neurology, 16, 581–584.
Doo, S., & Wing, Y. K. (2006). Sleep problems of children with pervasive developmental disorders: Correlation with parental stress. Developmental Medicine and Child Neurology, 48, 650–655.
Einfield, S. L., & Tonge, B. J. (1989). The Developmental Behaviour Checklist. Melbourne Australia: Monash University Centre For Developmental Psyhciatry.
Galli-Carminati, G., Deriaz, N., & Bertschy, G. (2009). Melatonin in the treatment of chronic sleep disorders in adults with autism: A retrospective study. Swiss med weekly, 139(19–20), 293–296.
Garstang, J., & Wallis, M. (2006). Randomised controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child: Care, Health and Development, 32, 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. Journal of Autism and Developmental Disorders, 36, 741–752.
Goldberg, D. (1992). General health questionnaire (GHQ-12). Windsor, UK: Nfer-Nelson.
Gordon, N. (2000). The therapeutics of Melatonin: a paediatric perspective. Brain and Development, 22, 213–217.
Hayashi, E. (2000). Effect of melatonin on sleep-wake rhythm: The sleep diary of an autistic male. Psychiatry and Clinical Neurosciences, 54(3), 383.
Hayashi, E. (2001). Seasonal changes in sleep and behavioural problems in a prepubescent case with autism. Psychiatry and Clinical Neurosciences, 55, 223–224.
Hoshino, Y., Watanabe, H., Yashima, Y., Kaneko, M., & Kumashiro, H. (1984). An investigation on the sleep disturbance of autistic children. Folia Psychiatrica et Neurologica Japonica, 38, 45–51.
Ishizaki, A., et al. (1999). Usefulness of melatonin for developmental sleep and emotional/behavior disorders-studies of melatonin trial on 50 patients with developmental disorders. No To Hattatsu, 31(5), 428–437.
Ivanenko, A., Crabtree, V. M., Tauman, R., et al. (2003). Melatonin in children and adolescents with insomnia: a retrospective study. Clinical Paediatrics, 42, 51–58.
Jan, M. S., et al. (1994). The treatment of sleep disorders with melatonin. Developmental Medicine and Child Neurology, 36, 97–107.
Jan, J. E., Freeman, R. D., & Fast, D. K. (1999). Melatonin treatment of sleep-wake cycle disorders in children and adolescents. Developmental Medicine and Child Neurology, 41, 491–500.
Lockley, S. W., Skene, D. J., Arendt, J., Tabandeh, H., Bird, A. C., & Defrance, R. (1997). Relationship between melatonin rhythms and visual loss in the blind. The Journal of Clinical Endocrinology and Metabolism, 82, 3763–3770.
Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism diagnostic interview—revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685.
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., et al. (2001). The autism diagnostic observation schedule—generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 205–223.
Malow, B. A., Marzec, M. L., McGrew, S. G., Wang, L., Henderson, L. M., & Stone, W. L. (2006). Characterising sleep in children with autism spectrum disorders: A multidimensional approach. Sleep, 29, 1563–1571.
McArthur, A. J., & Budden, S. S. (1998). Sleep dysfunction in Rett syndrome: A trial of exogenous melatonin treatment. Developmental Medicine and Child Neurology, 40(3), 186–192.
Melke, J., Goubran-Botros, H., Chaste, P., Betancur, C., Nygren, G., Anckarsäter, H., et al. (2008). Abnormal melatonin synthesis in autism spectrum disorders. Molecular Psychiatry, 13(1), 90–98.
Minde, K., Faucon, A., & Faulkner, S. (1994). Sleep problems in toddlers, effects of treatment on their daytime behaviour. Journal of American Academy of Child and Adolescent Psychiatry, 33, 1114–1121.
Miyamoto, A., Oki, J., Takahashi, S., et al. (1999). Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome. Brain and Development, 21, 59–62.
Mulchahey, J. J., Goldwater, D. R., & Zemlan, F. P. (2004). A single blind placebo controlled across groups dose escalation study of the safety, tolerability, pharmacokinetics, pharmacodynamics of the melatonin analog Beta-methyl-6-chloromelatonin. Life Sciences, 75, 1843–1856.
National Autistic Society (2009, December 15th). Sleep and autism: Helping your child. Retrieved from http://www.nas.org.uk/nas/jsp/polopoly.jsp?d=528&a=3376.
Niederhofer, H., et al. (2003). Brief report: Melatonin facilitates sleep in individuals with mental retardation and insomnia. Journal of Autism and Developmental Disorders, 33(4), 469–472.
Nir, I., Meir, D., Zilber, N., Knobler, H., & Hadjez, J. (1995). Brief report: Circadian melatonin, thyroid stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. Journal of Autism and Developmental Disorders, 25, 641–654.
Norton, P., & Drew, C. (1994). Autism and potential family stressors. The American Journal of Family Therapy, 22(1), 67–76.
O’Connell A, Chapparo C (2002) The trouble with sleeping can a waterbed help? Inaugural World Autism Conference.
Patzold, L. M., Richdale, A. L., & Tonge, B. J. (1998). An investigation into the sleep characteristics of children with autism and Asperger’s disorder. Journal of Paediatrics and Child Health, 34, 528–533.
Phillips, L., & Appleton, R. (2004). Systematic review of melatonin treatment in children with neurodevelopmental disabilities and sleep impairment. Developmental Medicine and Child Neurology, 46(11), 771–775.
Quine, L. (1992). Severity of sleep problems in children with severe learning disabilities: Description and correlates. Journal of Community and Applied Social Psychology, 2, 247–268.
Quine, L. (2001). Sleep problems in primary school children: Comparison between mainstream and special school children care. Health and Development., 37(3), 201–221.
Ramachandani, P., Wiggs, L., Webb, V., & Stores, G. (2000). A systematic review of treatments for settling problems and night waking in young children. BMJ, 320, 209–213.
Richdale, A. L. (1999). Sleep problems in autism: Prevalence, cause and intervention. Developmental Medicine and Child Neurology, 41, 60–66.
Sack, R. L., Hughs, R. J., Edgar, D. M., & Lewy, A. J. (1997). Sleep-promoting effects of melatonin. At what dose, in whom, under what circumstances, and by what mechanisms? Sleep, 20, 908–915.
Sheldon, S. (1998). Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet, 351, 1254.
Simonds, J. F., & Parraga, H. (1982). Prevalence of sleep disorders and sleep behaviours in children and adolescents. Journal of the American Academy of Child Psychiatry, 21, 383–388.
Smits, M. G., Nagtegaal, E. E., Van Der Heijden, R., et al. (2001). Melatonin for chronic onset sleep disorder in children: A randomised placebo-controlled trial. Journal of Child Neurology, 16, 86–92.
Smits, M. G., Van Stel, H. F., Van Der Heijden, R., et al. (2003). Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: A randomised placebo-controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry, 42, 1286–1293.
Stores, G. (2003). Medication for sleep wake disorders. Archives of Disease in Childhood, 88, 899–903.
Sutherland, E. R., Martin, R. J., Ellison, M. C., & Kraft, M. (2002). Immunomodulatory effects of melatonin in asthma. American Journal of Respiratory Critical care Medicine, 166, 1055–1061.
Tuchman, R., & Rapin, I. (2002). Epilepsy in autism. Lancet Neurology, 1(6), 352–358.
WHO (1993). The ICD—10 Classification of mental and behavioural disorders:- Diagnostic Criteria for Research: General World Health Organisation.
Wasdell, M. B., Jan, J. E., Bomben, M. M., Freeman, R. D., Rietveld, W. J., Tai, J., et al. (2008). A randomised, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. Journal of Pineal Research, 44, 57–64.
Weiskop, S., Richdale, A., & Matthews, J. (2005). Behavioural treatment to reduce sleep problems in children with autism or fragile X syndrome. Developmental Medicine and Child Neurology, 47, 94–104.
Wiggs, L., & Stores, G. (2001). Behavioural treatment for sleep problems in children with severe intellectual disabilities and daytime challenging behaviour: Effect on mothers and fathers. British Journal of Health Psychology, 6(3), 257–269.
Wiggs, L., & Stores, G. (2004). Sleep patterns and sleep disorders in children with autism spectrum disorders: Insights using parent report and actigraphy. Developmental Medicine and Child Neurology, 46, 372–380.
World Health Organisation (1993). The ICD – 10 Classification of Mental and Behavioural Disorders:- Diagnostic Criteria for Research: General World Health Organisation.
This research was supported by grants from the York Innovations Fund and the London Law Trust. It was given ethical approval by York Research Ethics Committee and sponsored by Selby and York (North Yorkshire and York) PCT.Thanks to Than Lwin, Anne Worrall-Davies, Clare Dover, Helen Pearce and Greg Richardson for their support on the trial steering groups. Thanks also to Clive Nicholson, the trial monitor and to Chris Davey for her support with data entry.
About this article
Cite this article
Wright, B., Sims, D., Smart, S. et al. Melatonin Versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial. J Autism Dev Disord 41, 175–184 (2011). https://doi.org/10.1007/s10803-010-1036-5
- Autism spectrum disorders