Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials

To evaluate the efficacy and safety of melatonin in the treatment of sleep onset insomnia in children and adolescents.Electronic databases and bibliographies of relevant reports were searched for randomized, placebo-controlled, clinical trials that used melatonin in children and adolescents with sleep onset insomnia. The quality of the included studies was assessed by the Cochrane Collaboration's risk-of-bias method. The mean differences (MD) and the odds ratios (OR) with 95% confidence interval (CI) were estimated by a random-effects model. Primary outcomes were sleep onset time (SOT), drop-out for all causes and drop-out for adverse events. Secondary outcomes included dim light melatonin onset (DLMO), sleep onset latency (SOL), total sleep time (TST), light-off time, and wake-up time.Seven trials with 387 participants were finally included after a systematic search. The overall quality of the included studies was low to moderate. SOT in patients receiving melatonin advanced more than patients receiving placebo (MD = -0.62 h, 95% CI -0.80, -0.45), as well as DLMO (MD = -0.82 h, 95% CI -1.23, -0.41). No differences were found in the outcome of drop-out for all causes (OR = 1.51, 95% CI 0.57, 4.05) or drop-out for adverse events (OR = 3.35, 95% CI 0.13, 86.03). Severe adverse events, migraine, and mild generalized epilepsy were reported in two cases. SOL decreased and TST increased, MD = -0.36 h (95% CI -0.49, -0.24) and MD = 0.38 h (95% CI 0.09, 0.66), respectively. Light-off time and wake-up time did not differ significantly.Melatonin was an effective and tolerable drug in the short-term treatment of sleep onset insomnia in children and adolescents. More studies, especially in adolescents, are needed to investigate the efficacy and safety of melatonin.