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Melatonin Use in the ICU: A Systematic Review and Meta-Analysis

Tang BHY, Manalo J, Chowdhury SR, Aldrich JM, Weinhouse GL, Cordoza M, Louzon PR, Balas MC et al.

Critical care medicine, 2025

3,895 participants · 13 citations

Abstract

OBJECTIVES: Melatonin has wide-ranging effects on the body, including the regulation of circadian rhythm, and potentiation of cellular immune and antioxidant activities. In critically ill patients, endogenous melatonin has been shown to be markedly deranged and reduced. Therefore, the purpose of this systematic review and meta-analysis was to determine if exogenous supplementation of melatonin improves patient-centered outcomes.

DATA SOURCES: We searched five electronic databases.

STUDY SELECTION: Randomized clinical trials (RCTs) that compared melatonin to no melatonin in adults admitted to the ICU were identified.

DATA EXTRACTION: We aggregated data as relative risks, mean differences (MDs), and standard mean differences (SMDs) using a random-effects model. Supporting evidence for each effect was evaluated for certainty using the Grading Recommendations, Assessment, Development, and Evaluations approach.

DATA SYNTHESIS: In total, 32 RCTs ( n = 3895 patients) were included. We found that melatonin may reduce delirium (relative risk [RR] 0.72; 95% CI, 0.58-0.89; low certainty), may slightly reduce ICU length of stay (MD -0.57 d; 95% CI, -0.95 to -0.18 d; low certainty), and may improve reported sleep quality (SMD 0.54; 95% CI, 0.01-1.07; low certainty). Melatonin may result in a slight reduction in the frequency of adverse events (low certainty). Evidence was uncertain with regards to the frequency of sleep awakenings, anxiety level, agitation, and post-traumatic stress…

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: 3,895 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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