AIM: Failure of dental treatment caused by anxiety is a common problem in children. Oral midazolam has been the most commonly used premedication for pediatric patient but the use of midazolam may be associated with paradoxical reactions in children. Melatonin may induce a natural sleepiness and improve sedation. We have investigated premedication with melatonin compared with midazolam in children under nitrous oxide/oxygen (N(2)O/O(2)) sedation for dental treatment. METHODS: In a randomized study, 60 children received either 3 mg of melatonin [Melatonina (3 mg(R)) 60 min before the procedure (n = 15); group I], 0.5 mg.kg(-1) melatonin 60 min before the procedure (n = 15; group II), 0.75 mg.kg(-1) midazolam [Dormicum (15 mg/3 ml (R)) 15 min before the procedure (n = 15); group III] or 3 ml of 0.09 NaCl 15 min (n = 7) or 60 min before the procedure (n = 8; group IV) orally. The children were sedated with 40/60% N(2)O/O(2) inhalation. The heart rate and O(2) saturation were monitored during the treatment period. The level of sedation was assessed according to the Ramsay Sedation Scale. The children's sedation success during dental treatment was classified. The sedation success and other sedation-related events recorded. Comparisons among the four groups were made using one-way anova or Kruskal-Wallis test, and if any significant differences were noted, the Tukey's HSD or Mann-Whitney U-test were used for intergroup comparisons. All differences were considered significant at P < 0.05. RESULTS: The evaluation of sedation success was as follows: group I: satisfactory (n = 1), average satisfactory (n = 4), and unsatisfactory (n = 10); group II: satisfactory (n = 2), average satisfactory (n = 3), and unsatisfactory (n = 10); group III: satisfactory (n = 9), average satisfactory (n = 6); and group IV: satisfactory (n = 1), average satisfactory (n = 3), and unsatisfactory (n = 11). CONCLUSION: In these doses and clinical conditions, melatonin was similar to that of placebo and did not contribute to N(2)O/O(2) sedation of anxious children.

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.

OBJECTIVE: To evaluate the efficacy of sleep hygiene and melatonin treatment for initial insomnia in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Twenty-seven stimulant-treated children (6-14 years of age) with ADHD and initial insomnia (>60 minutes) received sleep hygiene intervention. Nonresponders were randomized to a 30-day double-blind, placebo-controlled, crossover trial of 5-mg pharmaceutical-grade melatonin provided by the study's sponsor. RESULTS: Sleep hygiene reduced initial insomnia to <60 minutes in 5 cases, with an overall effect size in the group as a whole of 0.67. Analysis of the trial data able to be evaluated showed a significant reduction in initial insomnia of 16 minutes with melatonin relative to placebo, with an effect size of 0.6. Adverse events were generally mild and not different from those recorded with placebo treatment. The effect size of the combined sleep hygiene and melatonin intervention from baseline to 90 days' posttrial was 1.7, with a mean decrease in initial insomnia of 60 minutes. Improved sleep had no demonstrable effect on ADHD symptoms. CONCLUSION: Combined sleep hygiene and melatonin was a safe and effective treatment for initial insomnia in children with ADHD taking stimulant medication.

CRD SUMMARY: This well-conducted review found improvements in time to sleep onset in children with neurodevelopmental disabilities and sleep impairment who were taking melatonin compared with placebo. However, the evidence was based on three trials of just 35 children. The authors highlighted the need for further, adequately powered trials to more clearly determine potential benefits and risks.

BACKGROUND: There is a high prevalence of chronic sleep-wake cycle disorders in developmentally and neurologically disabled children. Such disorders are often resistant to hypnotic and psychotropic drugs. Administration of exogenous melatonin can have an effect upon the circadian rhythm and establish a normal sleep-wake cycle. MATERIAL AND METHODS: Medline, Premedline and EBM Reviews were searched for articles on melatonin treatment of sleep-wake cycle disorders in children. Additionally, sleep was registered systematically in 15 developmentally or neurologically disabled children treated with melatonin. RESULTS AND INTERPRETATION: The search identified 75 articles of which 33 included neurologically or developmentally disabled children. Reported results generally indicate that melatonin improves sleep-wake cycle disorders in these children. However, the majority of studies were open, and knowledge about side effects and long-term effects is limited. Our own experience is in accordance with the literature; melatonin had positive effects in 13 children. Suggestions for practical use of melatonin in disabled children are presented.

BACKGROUND: Exogenous melatonin helps in regulating the circadian rhythm and is widely used for the management of sleep disorders in visually impaired children.  OBJECTIVES: The aim of the review was to assess melatonin therapy for treatment of non-respiratory sleep disorders in visually impaired children, with regard to improvement in sleep habit, sleep scheduling and sleep maintenance, when compared with placebo or no treatment. SEARCH STRATEGY: We searched the following databases between February 2011 and July 2011: the Cochrane Central Register of Controlled Trials (CENTRAL) 2011(1) searched on 4th February 2011; MEDLINE (1950 to June Week 3, 2011) searched on 20th June 2011; EMBASE (1980 to June Week 4, 2011) searched on 7th July 2011; CINAHL (1937 to 21 September 2011); the metaRegister of Controlled Trials (this includes ClinicalTrial.gov) searched 20 July 2011, and reference lists of papers identified after initial screening.  SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) and quasi-RCTs, including cross-over studies. Treatment would be exogenous melatonin. Control groups could be placebo, other medication for sleep disorders or no treatment. Outcomes sought were improved sleep with regard to timing and duration, quality of life and adverse events.  DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion in the review. MAIN RESULTS: We did not find any studies fulfilling the inclusion criteria, therefore no outcome data are reported. We identified nine studies after initial screening and, after further evaluation, we excluded these. The excluded studies involved a total of 163 individuals aged two years to 18 years. We excluded studies for three main reasons: they were non-randomized or case series studies, they were studies of people over 18 years of age or even where the study was randomised, the study population was mixed and results pertaining to the visually impaired cohort could not be independently evaluated. No significant adverse effects of melatonin were reported in these excluded studies. AUTHORS' CONCLUSIONS: There is currently no high quality data to support or refute the use of melatonin for sleep disorders in visually impaired children. Placebo-controlled trials examining important clinical outcomes such as sleep quality, sleep latency, duration of sleep and night-time awakenings are needed. As the numbers of children meeting study inclusion criteria are likely to be low at individual sites, multicentre collaboration between developmental paediatricians, sleep physicians and other health care professionals is essential to achieve sufficient sample size for controlled studies. Such collaboration would help facilitate local recruitment at multiple sites, with study oversight being provided by paediatricians with expertise in sleep disorders. Participation of collaborators with experience in evidence-based practice research is also desirable due to the lack of protocols on melatonin therapy in the target population.

RECORD STATUS: This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database. CITATION: Appleton RE, Jones AP, Gamble C, Williamson PR, Wiggs L, Montgomery P, Sutcliffe A, Barker C, Gringras P. The use of MElatonin in children with Neurodevelopmental Disorders and impaired Sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS) Health Technology Assessment 2012; 16(40): 1-239

This study explored the safety and efficacy of synthetic melatonin in the treatment of sleep problems in 20 children with developmental disabilities, in a randomized, double-blind, placebo-controlled 6-week trial of melatonin versus placebo. All but 2 children fell asleep more quickly when receiving melatonin than placebo. Overall, the greater the sleep latency (time to fall asleep) was at baseline or when receiving placebo, the more pronounced was the decrease in sleep latency with melatonin. The effect of melatonin on sleep latency was significant (P < .05). The duration of sleep while receiving melatonin was significantly greater than baseline (P < .007) but was not significantly different from placebo, and no difference in the number of awakenings was noted. No side effects were reported. Eleven of 18 parents (61%) correctly identified the weeks their child received melatonin. This study suggests that synthetic melatonin reduces sleep latency in children with developmental disabilities.

PURPOSE: Several studies have reported that sevoflurane was associated with a relatively high incidence of emergence agitation in children even in the absence of any surgical intervention. The aim of this study was to compare early agitation characteristics of oral melatonin, dexmedetomidine, and midazolam premedication in children who were given sevoflurane anesthesia for esophageal dilatation. METHODS: Following Internal Review Board approval and parental informed consent, 100 ASA physical status I-II children (3-9 years old) who were scheduled to undergo general anesthesia for esophageal dilatation procedures were enrolled. The patients were randomly assigned to four groups (n = 25 in each). The premedications in the groups were saline (group P), dexmedetomidine 2.5 μg/kg (group D), 0.5 mg/kg midazolam (group MD), and melatonin 0.1 mg/kg (group ML), given orally. All premedication drugs were given with paracetamol 2-2.5 mg/kg to be easily drinkable 40-45 min before anesthesia induction. Anesthesia was maintained with sevoflurane 2-4%, N(2)O 50% in oxygen. No supplemental analgesic agent was given, and an emergence agitation scale (EAS) was measured on admission to the PACU, then every 5 min, and recorded during the postoperative period: 1, awake and calm, cooperative; 2, crying, requires consoling; 3, irritable/restless, screaming, inconsolable; 4, combative, disoriented, thrashing. Children with an agitation score of 3 or 4 were classified as agitated. RESULTS: There were no significant differences among the four groups demographically. The emergence agitation scale was higher in the placebo group than in the others at 5, 10, and 15 min postoperatively (P < 0.001). EA was similar among group D, group MD, and group ML. CONCLUSION: We found that oral melatonin, dexmedetomidine, and midazolam reduced the incidence of emergence agitation in children after sevoflurane anesthesia.

RECORD STATUS: None CITATION: NHS Quality Improvement Scotland. Melatonin to assist in the management of sleep disorders in children with neuro-developmental disorders. Glasgow: Quality Improvement Scotland (NHS QIS ). Evidence Note 14. 2006