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

OBJECTIVE: To evaluate the efficacy and safety of melatonin in the treatment of sleep onset insomnia in children and adolescents. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: To assess the efficacy and tolerability of trazodone compared with placebo in patients with insomnia. METHODS: Electronic databases were searched and relevant reports were hand-screened to identify eligible trials. Only randomized placebo-controlled trials were included. Standardized mean differences (SMD) and the odds ratios (OR) were estimated using a random-effect model. Primary efficacy outcomes included sleep efficiency (SE%) and self-reported sleep quality (SQ). Secondary efficacy outcomes included sleep latency (SL), total sleep time (TST), the number of awakenings (NAs), waking time after sleep onset (WASO). Tolerability outcome was measured by the number of patients who discontinued for adverse events and acceptability outcome was measured by the number of patients who discontinued for all causes. RESULTS: Seven trials involving 429 patients were included. There was no significant improvement for trazodone in SE% (SMD = 0.09, 95% confidence interval (CI) -0.19 to 0.38, P = 0.53) with a non-significant heterogeneity (I2 = 0%, P = 0.59). However, patients receiving trazodone perceived better SQ than those receiving the placebo (SMD = -0.41, 95% CI -0.82 to -0.00, P = 0.05) with a non-significantly moderate heterogeneity (I2 = 65%, P = 0.06). As to secondary efficacy outcomes, we only found a significant reduction for trazodone in NAs (SMD = -0.51, 95%CI -0.97 to -0.05) compared to the placebo, with non-significant differences found in SL, TST, or WASO between trazodone and placebo. Moreover, no significant difference was found in the outcome of tolerability or acceptability. CONCLUSIONS: Trazodone was effective in sleep maintenance by decreasing the number of early awakenings and it could significantly improve perceived sleep quality, although there were no significant improvements in sleep efficiency or other objective measures. Trazodone however, presented good tolerance in the short-term treatment of insomnia.