Skip to main content

Advertisement

SpringerLink
Log in

Melatonin Versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

  • ORIGINAL PAPER
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

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 via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Armour, D., & Paton, C. (2004). Melatonin in the treatment of insomnia in children and adolescents. Psychiatric Bulletin, 28, 222–224.

    Article  Google Scholar 

  • Bramble, D., & Feehan, C. (2005). Psychiatrists’ use of melatonin with children. Child and Adolescent Mental Health, 10(3), 145–149.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Einfield, S. L., & Tonge, B. J. (1989). The Developmental Behaviour Checklist. Melbourne Australia: Monash University Centre For Developmental Psyhciatry.

    Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Goldberg, D. (1992). General health questionnaire (GHQ-12). Windsor, UK: Nfer-Nelson.

    Google Scholar 

  • Gordon, N. (2000). The therapeutics of Melatonin: a paediatric perspective. Brain and Development, 22, 213–217.

    Article  PubMed  Google Scholar 

  • Hayashi, E. (2000). Effect of melatonin on sleep-wake rhythm: The sleep diary of an autistic male. Psychiatry and Clinical Neurosciences, 54(3), 383.

    Article  PubMed  Google Scholar 

  • Hayashi, E. (2001). Seasonal changes in sleep and behavioural problems in a prepubescent case with autism. Psychiatry and Clinical Neurosciences, 55, 223–224.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Jan, M. S., et al. (1994). The treatment of sleep disorders with melatonin. Developmental Medicine and Child Neurology, 36, 97–107.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Norton, P., & Drew, C. (1994). Autism and potential family stressors. The American Journal of Family Therapy, 22(1), 67–76.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Quine, L. (2001). Sleep problems in primary school children: Comparison between mainstream and special school children care. Health and Development., 37(3), 201–221.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Richdale, A. L. (1999). Sleep problems in autism: Prevalence, cause and intervention. Developmental Medicine and Child Neurology, 41, 60–66.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Sheldon, S. (1998). Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet, 351, 1254.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Stores, G. (2003). Medication for sleep wake disorders. Archives of Disease in Childhood, 88, 899–903.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Tuchman, R., & Rapin, I. (2002). Epilepsy in autism. Lancet Neurology, 1(6), 352–358.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • World Health Organisation (1993). The ICD – 10 Classification of Mental and Behavioural Disorders:- Diagnostic Criteria for Research: General World Health Organisation.

Download references

Acknowldgments

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.

Author information

Author notes

  1. Clare Whitton

    Present address: Tees, Esk and Wear Valleys NHS Foundation Trust, Darlington, Durham, England, UK

  2. Jenni Jardine

    Present address: Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, England, UK

  3. Nicola McCaffrey

    Present address: NHS Grampian, Aberdeen, Aberdeenshire, Scotland, UK

  4. Jeremy Miles

    Present address: RAND Corporation, Santa Monica, CA, USA

Authors and Affiliations

  1. Lime Trees Child, Adolescent and Family Unit, 31 Shipton Road, York, North Yorkshire, YO30 5RE, England, UK

    Barry Wright, Ben Alderson-Day, Clare Whitton, Heather Tomlinson, Sophie Bennett, Jenni Jardine & Nicola McCaffrey

  2. Hillbrook Child and Family Centre, Hillbrook, Mayfield Road, Keighley, West Yorkshire, BD20 6LD, England, UK

    David Sims

  3. Dragon Parade Clinic, 2 Dragon Parade, Harrogate, North Yorkshire, HG1 5BY, England, UK

    Siobhan Smart

  4. Royal Bolton Hospital, Minerva Road, Farnworth, Bolton, LN, BL4 0JR, England, UK

    Ahmed Alwazeer

  5. Hull York Medical School, John Hughlings Jackson Building, University of York, Heslington, York, North Yorkshire, YO10 5DD, England, UK

    Victoria Allgar

  6. University of York, Heslington, York, YO10 5DD, England, UK

    Charlotte Leyland

  7. York Hospital, Wigginton Road, York, North Yorkshire, YO31 8HE, England, UK

    Christine Jakeman & Jeremy Miles

Authors
  1. Barry Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Sims
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siobhan Smart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmed Alwazeer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ben Alderson-Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Victoria Allgar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Clare Whitton
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Heather Tomlinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sophie Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jenni Jardine
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Nicola McCaffrey
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Charlotte Leyland
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Christine Jakeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jeremy Miles
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Barry Wright.

Rights and permissions

Reprints and permissions

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-010-1036-5

Keywords

Search

Navigation