Network Meta-analysis of Melatonin Receptor Agonists in the Treatment of Primary Sleep Disorders: Efficacy and Safety Profile
Abstract
Melatonin receptor agonists represent an important class of medications for primary sleep disorders, but their comparative efficacy and safety remain incompletely understood. The study was to conduct a comprehensive network meta-analysis (NMA) comparing the efficacy and safety of melatonin receptor agonists for the treatment of primary sleep disorders.
We searched multiple databases from inception to January 2025 for randomised controlled trials (RCTs) evaluating melatonin receptor agonists (ramelteon, tasimelteon, agomelatine and prolonged-release melatonin) in adults with primary sleep disorders. The primary efficacy outcomes were sleep onset latency (SOL), total sleep time (TST) and sleep efficiency. Safety outcomes included adverse events (AEs) and discontinuations. We performed a Bayesian NMA using random-effects models and assessed the certainty of evidence using the CINeMA approach.
Fifty-nine RCTs (12,437 participants) were included. All melatonin receptor agonists significantly reduced SOL compared to placebo, with mean differences ranging from −14.8 min (95% credible interval [CRL]: −19.2 to −10.4) for ramelteon to −8.2 min (95% CrI: −13.7 to −2.7) for prolonged-release melatonin. For TST, significant improvements compared to placebo were observed for ramelteon, tasimelteon and agomelatine, but not for prolonged-release melatonin. In head-to-head comparisons, no statistically significant differences were observed among melatonin receptor agonists for most efficacy…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 12,437 participants or records.
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