Systematic review of melatonin treatment in children with neurodevelopmental disabilities and sleep impairment
Child; Humans; Wakefulness/physiology; Brain/physiopathology; Melatonin/therapeutic use; Antioxidants/therapeutic use; Developmental Disabilities/drug therapy/epidemiology/physiopathology; Sleep Wake Disorders/epidemiology; sleep disturbance/disorders; Rett syndrome; pharmacologic intervention; melatonin
Sleep disturbances in children with neurodevelopmental disabilities are common and frequently difficult to treat with conventional pharmacological and behavioural methods. Melatonin is a pineal hormone known to be important in the regulation of the circadian rhythm, including the sleep-wake cycle. This systematic review of available evidence from randomized clinical trials assesses whether melatonin plays a beneficial role in these children and, in particular, its effect on total sleep time, time to sleep onset (sleep latency), and number of awakenings. We also looked at a parental view of the effect. Randomized clinical trials were identified where oral melatonin was compared with a placebo in children with any type of neurodevelopmental disability and associated sleep disturbance. Only three studies, reporting a total of 35 children, fulfilled the criteria for inclusion. The two studies that reported time to sleep onset showed a significant decrease (p<0.05) in this specific outcome where melatonin was compared with a placebo. There was no significant effect of melatonin compared with a placebo on the other outcome measures of total sleep time, night-time awakenings, and parental opinions. Despite the extremely limited randomized clinical trial data, melatonin appears to remain a commonly prescribed drug for disturbed sleep in children with neurodevelopmental abnormalities.
Phillips L; Appleton R E
Developmental Medicine and Child Neurology
2004
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1017/s001216220400132x" target="_blank" rel="noreferrer noopener">10.1017/s001216220400132x</a>
The use of Melatonin in children with Neurodevelopmental Disorders and impaired Sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS)
insomnia; Health Care Sciences & Services; autism spectrum disorders; controlled-trial; exogenous melatonin; handicapped-children; improves sleep; onset; phase; rett-syndrome; serum melatonin; syndrome; young-adults; sleep disturbance/disorders; neurodevelopmental disorders; pharmacologic intervention; melatonin
Background: Difficulties in initiating and maintaining sleep are common in children with neurodevelopmental disorders. Melatonin is unlicensed in children yet widely prescribed for sleep problems. Objective: To determine whether or not immediate-release melatonin is beneficial compared with placebo in improving total duration of night-time sleep in children with neurodevelopmental problems. Design: Randomised, double-blind, placebo-controlled, parallel study. Setting: Hospitals throughout England and Wales recruited patients referred by community paediatricians and other clinical colleagues. Participants: Children with neurodevelopmental problems aged from 3 years to 15 years 8 months who did not fall asleep within 1 hour of lights out or who had <6 hours of continuous sleep. Before randomisation, patients meeting eligibility criteria entered a 4- to 6-week behaviour therapy period in which a behaviour therapy advice booklet was provided. Sleep was measured using sleep diaries and actigraphy. After this period the sleep diaries were reviewed to determine if the sleep problem fulfilled the eligibility criteria. Eligible participants were randomised and followed for 12 weeks. Interventions: Melatonin or placebo capsules in doses of 0.5 mg, 2 mg, 6mg and 12 mg for a period of 12 weeks. The starting dose was 0.5 mg and the dose could be escalated through 2 mg and 6 mg to 12 mg during the first 4 weeks, at the end of which the child was maintained on that dose. Main outcome measures: The primary outcome was total night-time sleep time (TST) calculated using sleep diaries at 12 weeks compared with baseline. Secondary outcome measures included TST calculated using actigraphy data, sleep-onset latency (SOL) (time taken to fall asleep), sleep efficiency, Composite Sleep Disturbance Index score, global measure of child's sleep quality, Aberrant Behaviour Checklist, Family Impact Module of the Pediatric Quality of Life Inventory (PedsQL (TM)), the Epworth Sleepiness Scale, number and severity of seizures and adverse events. Salivary melatonin concentrations and association of genetic variants with abnormal melatonin production were also investigated. Results: A total of 275 children were screened to enter the trial; 263 (96%) children were registered and completed the 4- to 6-week behaviour therapy period and 146 (56%) children were randomised, of whom 110 (75%) contributed data for the primary outcome. The difference in TST time between the melatonin and placebo groups adjusted for baseline was 22.43 minutes [95% confidence interval (Cl) 0.52 to 44.34 minutes; p = 0.04] measured using sleep diaries. A reduction in SOL, adjusted for baseline, was seen for melatonin compared with placebo when measured by sleep diaries (-37.49 minutes, 95% CI -55.27 to -19.71 minutes; p < 0.0001) and actigraphy (-45.34 minutes, 95% CI -68.75 to -21.93 minutes; p=0.0003). There were no significant differences between the two groups in terms of the reporting of adverse events. The results of other secondary outcomes favoured melatonin but were not statistically significant. Conclusions: On average, the children treated with melatonin slept 23 minutes longer than those in the placebo group; however, the upper limit of the confidence interval was less than 1 hour, the minimum clinically worthwhile difference specified at the outset of the trial. Melatonin is effective in reducing SOL in children with neurodevelopmental delay by a mean of 45 minutes; a value of 30 minutes was specified a priori to be clinically important. Future studies should be conducted over longer periods and directly compare different formulations of melatonin with conventional hypnotic and sedative medications. It would also be important to study groups of children with specific neurological disorders. Trial registration: Current Controlled Trials ISRCTN05534585.
Appleton R E; Jones A P; Gamble C; Williamson P R; Wiggs L; Montgomery P; Sutcliffe A; Barker C; Gringras P
Health Technology Assessment
2012
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3310/hta16400" target="_blank" rel="noreferrer noopener">10.3310/hta16400</a>