Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysis.
Study Goal
The researchers aimed to assess the efficacy of melatonin and ramelteon compared to placebo in improving sleep quantity and quality in individuals with insomnia disorder, while considering factors influencing their efficacy.
Results Summary
Prolonged-release (PR) melatonin showed small to medium effect sizes in reducing sleep onset latency (both subjective and objective) and improving objective sleep efficiency, with larger effects in patients aged ≥55. Ramelteon demonstrated large effect sizes on total sleep time and sleep onset latency at 4 weeks and in long-term use.
Population
Individuals with insomnia disorder, including a subgroup with a mean age ≥55.
Effective Dosage
Not specified
Duration
Varied (acute and long-term effects assessed)
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
prolonged release (PR) melatonin | decrease | subjective sleep onset latency (sSOL) | patients with insomnia disorder | weighted difference = -6.30 min | appears efficacious with a small to medium effect size | #1 |
prolonged release (PR) melatonin | decrease | objective sleep onset latency (oSOL) | patients with insomnia disorder | weighted difference = -5.05 min | appears efficacious with a small to medium effect size | #2 |
prolonged release (PR) melatonin | increase | objective sleep efficiency (oSE) | patients with insomnia disorder | weighted difference = 1.91% | appears efficacious with a small to medium effect size | #3 |
prolonged release (PR) melatonin | increase | objective sleep efficiency (oSE) | patients with a mean age ≥55 | weighted difference = 2.95% | was efficacious on oSE with a large effect size | #4 |
ramelteon | increase | objective total sleep time (oTST) | patients with insomnia disorder | weighted difference = 17.9 min | was efficacious with a large effect size at 4 weeks | #5 |
ramelteon | increase | subjective total sleep time (sTST) | patients with insomnia disorder | weighted difference = 11.7 min | was efficacious with a large effect size at 4 weeks | #6 |
ramelteon | decrease | subjective sleep onset latency (sSOL) | patients with insomnia disorder | weighted difference = -8.74 min | was efficacious with a large effect size at 4 weeks | #7 |
ramelteon | decrease | objective sleep onset latency (oSOL) | patients with insomnia disorder | weighted difference = -14 min | was efficacious with a large effect size at 4 weeks | #8 |
ramelteon | increase | objective total sleep time (oTST) | patients with insomnia disorder | weighted difference = 2.02 min | has a large effect size on oTST | #9 |
ramelteon | increase | subjective total sleep time (sTST) | patients with insomnia disorder | weighted difference = 14.5 min | has a large effect size on sTST | #10 |
Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was conducted following PRISMA criteria, to assess the efficacy of melatonin and ramelteon compared with placebo on sleep quantity and quality in insomnia disorder, while also considering factors that may impact their efficacy. This review included 22 studies, with 4875 participants, including 925 patients treated with melatonin, 1804 treated with ramelteon and 2297 receiving a placebo. Most studies evaluated the acute efficacy of prolonged release (PR) melatonin in insomnia disorder. Compared with placebo, PR melatonin appears efficacious with a small to medium effect size on subjective sleep onset latency (sSOL) (p = 0.031; weighted difference = -6.30 min), objective sleep onset latency (oSOL) (p < 0.001; weighted difference = -5.05 min), and objective sleep efficiency (oSE) (p = 0.043; weighted difference = 1.91%). For the subgroup mean age of patients ≥55, PR melatonin was efficacious on oSE with a large effect size (p < 0.001; weighted difference = 2.95%). Ramelteon was efficacious with a large effect size at 4 weeks on objective total sleep time (oTST) (p = 0.010; weighted difference = 17.9 min), subjective total sleep time (sTST) (p = 0.006; weighted difference = 11.7 min), sSOL (p = 0.009; weighted difference = -8.74 min), and oSOL (p = 0.017; weighted difference = -14 min). Regarding long-term effects, ramelteon has a large effect size on oTST (p < 0.001; weighted difference = 2.02 min) and sTST (p < 0.001; weighted difference = 14.5 min). PR melatonin and ramelteon appear efficacious compared with placebo for insomnia symptoms with PR melatonin showing mostly small to medium effect sizes. PR melatonin for individuals with a mean age ≥ 55 and ramelteon show larger effect sizes.