Falls and fractures associated with ramelteon use: A systematic review and meta-analysis

Hypnotics are associated with increased risk of falls and fractures. However, most studies evaluating the association between ramelteon, and these outcomes, are single-center and lack comprehensive analysis. We aimed to evaluate the association between ramelteon use and the risk of falls and fractures.

We systematically searched for the term "ramelteon" in the Medical Literature Analysis and Retrieval System Online via PubMed, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov. in January 7, 2025. Retrieved studies were assessed for risk of bias and analyzed for the association between ramelteon use and falls or fractures using a random-effects model based on the Sidik-Jonkman method, as well as inter-study heterogeneity using the I² statistic. Meta-analyses were conducted on seven observational studies and three randomized controlled trials.

Ramelteon use was not significantly associated with an increased fall risk (odds ratio: 1.26; 95 % confidence interval: 0.83-1.92; I² = 0 %). Analysis of fractures showed a potential increased risk with ramelteon use (risk ratio: 3.29; 95 % confidence interval: 0.53-20.45; I² = 0 %), although this was not statistically significant.

Ramelteon was not associated with a statistically significant increase in the risk of falls or fractures, regardless of the study design.