Melatonin for Delirium Prevention: The Sleep Hormone Doesn’t Pass the ICU Test

link.springer.com October 23, 2025

Despite its frequent occurrence and association with increased mortality in critically ill patients, delirium prevention remains challenging. A recent meta-analysis sought to resolve conflicting results from randomized controlled trials (RCTs) on the effectiveness of melatonin in preventing delirium onset.

No Reduction in Delirium: The analysis, focusing on the highest quality evidence (six RCTs, 2209 patients), found no significant difference in the incidence of delirium attributable to melatonin treatment (Risk Ratio [RR] 0.89, [95% CI 0.73–1.09]). This finding remained consistent even when including all thirteen available RCTs.

No Impact on Mortality: Similarly, the study found no association between melatonin use and patient mortality in either the primary (seven RCTs) or secondary (eight RCTs) analyses.

The results strongly suggest that melatonin does not reduce the incidence of delirium nor does it affect mortality in critically ill patients when compared to a placebo.