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Randomized Controlled Trial
. 2012 Nov 5:345:e6664.
doi: 10.1136/bmj.e6664.

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial

P Gringras  1 , C Gamble, A P Jones, L Wiggs, P R Williamson, A Sutcliffe, P Montgomery, W P Whitehouse, I Choonara, T Allport, A Edmond, R Appleton; MENDS Study Group
Affiliations
Randomized Controlled Trial

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial

P Gringras et al. BMJ. .

Abstract

Objective: To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders.

Design: 12 week double masked randomised placebo controlled phase III trial.

Setting: 19 hospitals across England and Wales.

Participants: 146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours' continuous sleep.

Interventions: Immediate release melatonin or matching placebo capsules administered 45 minutes before the child's bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment.

Main outcome measures: Total sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy.

Results: Melatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (-15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (-37.5 minutes, -55.3 to -19.7 minutes) and actigraphy (-45.3 minutes, -68.8 to -21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups.

Conclusions: Children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required.

Trial registration: ISRCT No 05534585.

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Conflict of interest statement

Competing interests: All 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.

Figures

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Screening, randomisation, and follow-up of children with neurodevelopmental disorders and sleep disorders allocated to melatonin or placebo
See this image and copyright information in PMC

Comment in

References

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