Efficacy and Safety of Ramelteon in the Reduction of Delirium and Duration of ICU Stay: A Randomized Placebo-Controlled Trial

Background Delirium and sleep disturbances are common in critically ill patients and are associated with adverse outcomes, including prolonged intensive care unit (ICU) stays. Ramelteon, a melatonin receptor agonist, may improve sleep and reduce delirium by regulating circadian rhythms. This study evaluated the efficacy of ramelteon in shortening ICU stay, decreasing delirium incidence and duration, and improving sleep quality in critically ill patients. Methods A randomized controlled trial was conducted with 60 critically ill patients allocated to either ramelteon (n = 30) or placebo (n = 30). Three participants in the ramelteon group and two in the placebo group were lost to follow-up, leaving 27 and 28 patients for final analysis, respectively. Outcomes included ICU stay duration, delirium frequency and duration, and sleep parameters (total sleep time, awakenings, and nights without awakenings). Statistical analyses were performed using unpaired t-tests and Fisher's exact test. Results The ramelteon group had a significantly shorter mean ICU stay (4.78 vs. 6.23 days, p = 0.0006) and a shorter duration of delirium (18.83 vs. 33.69 hours, p < 0.0001). Delirium incidence was lower in the ramelteon group (7/27, 25.93% vs. 13/28, 46.43%), but this difference was not statistically significant (p = 0.1625). Sleep quality improved significantly, with fewer awakenings per night (0.79 vs. 1.28, p < 0.0001) and more nights without awakenings (0.56 vs. 0.35, p < 0.0001). Conclusion Ramelteon was associated with a reduced ICU stay, shorter delirium duration, and improved sleep quality in critically ill patients. While its impact on delirium incidence was not statistically significant, the findings suggest a potential benefit in mitigating delirium severity and enhancing recovery. Further large-scale studies are needed to confirm these results.