Editorials

Treatment of sleep disorders with melatonin

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6968 (Published 05 November 2012) Cite this as: BMJ 2012;345:e6968
  1. Alexander Lerchl, professor of biology1,
  2. Russel J Reiter, professor2
  1. 1Jacobs University Bremen, D-28759 Bremen, Germany
  2. 2University of Texas Health Science Center, San Antonio, TX, USA
  1. a.lerchl{at}jacobs-university.de

Children with neurodevelopmental disability sleep better but may wake earlier

Melatonin (N-acetyl-5-methoxytryptamin) is synthesized in the pineal body exclusively during periods of darkness. It plays an important role in initiating and maintaining sleep. In elderly people, concentrations of endogenous melatonin usually decline, and this is often associated with insomnia.1 Treatment with melatonin is effective in restoring normal sleep and improving quality of life in people over 55 years of age.1 Melatonin has also been used to treat children with developmental disabilities and sleep difficulties. It has been shown to be preferable to hypnotics, such as clonidine and benzodiazepines, because it does not affect sleep architecture or have adverse side effects.2 3 4

In a linked research paper (doi:10.1136/bmj.e6664) Gringras and colleagues randomised 146 children with neurodevelopmental delay and other diseases (epilepsy or autistic spectrum disorder, or both) that are associated with sleep disorders (delayed sleep onset or poor sleep maintenance, or both) to treatment with melatonin or placebo.5 The double blind design allowed parents to increase the dose of melatonin from 0.5 mg to 12 mg in the melatonin group. Parents of children in the placebo group were also given the opportunity to increase the “dosage.” This aspect of the study conferred an important advantage over traditional single dose studies, where dose flexibility was not examined. The figure shows the proportion of children who received different doses of melatonin and placebo. Although most children in the placebo group rapidly progressed to the highest “dose,” those receiving melatonin remained at lower doses, which suggests that parents did not consider higher doses necessary. About a fifth of children in the melatonin group received only 0.5 mg, suggesting that this low dose is sufficient to improve sleep patterns in a subgroup of children.

Figure1

Proportion of children receiving different doses of melatonin or placebo5

The main effect of melatonin was a shortened latency of sleep onset, from 102 minutes at baseline to 55 minutes at week 12, as estimated by sleep diaries. Actigraphy recordings showed a similar trend (127 v 68 minutes). Melatonin prolonged total sleep time by 40 minutes (diaries) and 16 minutes (actigraphy). Analysis of parental questionnaires suggested that parents thought that melatonin improved their children’s quality of sleep and reduced their own daytime sleepiness. Overall, treatment with melatonin resulted in better and longer sleep, which was a clinically important finding.

Interestingly, children treated with melatonin woke up an average of 17 minutes earlier than before treatment began (baseline v week 12) and about 30 minutes earlier than those in the placebo group (in week 12). Exogenous melatonin not only induces and maintains sleep, but it also affects the timing of its own synthesis and release by binding to receptors at the suprachiasmatic nucleus, the biological clock.6 This follows the same principle as when using melatonin to treat people who have jet lag or sleep disorders related to shift work; melatonin is taken at the new time when sleep induction is required.7 In Gringras and colleagues’ study, therefore, administering melatonin at a particular time induced a time shift in the endogenous production of melatonin and resulted in earlier waking.

As the authors mention, future studies should use slow release formulations of melatonin or, even better, mixtures of fast release and slow release formulations. This would ensure both a rapid increase of melatonin for inducing sleep and long lasting high concentrations of melatonin for maintaining sleep. The findings of several studies now support the use of melatonin in the treatment of sleep disorders in neurodevelopmentally disabled children.2 3 5 Its use improves the quality of life for these children and may also benefit their families.

Notes

Cite this as: BMJ 2012;345:e6968

Footnotes

  • Research, doi:10.1136/bmj.e6664
  • Competing interests: Both authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

References