Melatonin supplementation reduces delirium incidence in critically ill patients: a systematic review and meta-analysis
Abstract
Background Delirium represents a common and severe neuropsychiatric complication among critically ill individuals, often leading to extended hospital stays, elevated mortality risk, and persistent cognitive decline. Disruption of circadian sleep-wake rhythms is a major pathogenic factor, implying that melatonin may hold therapeutic potential in this context. Nonetheless, evidence regarding the effectiveness of melatonin in preventing delirium among patients in intensive care unit (ICU) remains inconsistent. Objective This meta-analysis aimed to systematically evaluate the effects of melatonin and melatonin receptor agonists on the incidence and duration of delirium, length of ICU stay, and mortality among adult critically ill patients. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). A comprehensive search was performed in PubMed, Embase, Scopus, and Cochrane CENTRAL from inception until 10 October 2025. Only RCTs comparing melatonin or ramelteon with placebo or standard care in adult ICU patients were included. The primary outcome was the incidence of delirium. Secondary outcomes included duration of delirium, length of ICU stay, and overall mortality. Results A total of 22 RCTs involving 3706 patients were included. Pooled analysis demonstrated that melatonin administration was associated with a significant reduction in the incidence of delirium compared to the control group (Risk Ratio [RR] 0.75, 95% Confidence Interval…
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: 3,706 participants or records.
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