The effect of melatonin on delirium in hospitalised patients: A systematic review and meta-analyses with trial sequential analysis.

OBJECTIVES: Melatonin is an endogenous hormone, which regulates circadian rhythms and promotes sleep. In recent years, several randomised controlled trials examining the prophylactic use of melatonin to prevent delirium were published with conflicting findings. The primary aim of this review was to determine the effect of melatonin on the incidence of delirium in hospitalised patients. DATA SOURCES: MEDLINE, EMBASE and CENTRAL were systematically searched from their inception until December 2018. REVIEW METHODS: All randomised clinical trials were included. RESULTS: Sixteen trials (1634 patients) were included in this meta-analysis. Incidence of delirium was not significantly lower in patients who received melatonin, with an odd ratio, OR (95%Cl) of 0.55 (0.24-1.26); ρ = 0.16, certainty of evidence = low, trial sequential analysis = inconclusive. However, patients who randomised to melatonin had a significantly shorter length of stay in intensive care units, with a mean difference, MD (95%CI) of -1.84 days (-2.46, -1.21); ρ < 0.001. No differences were demonstrated in the need for physical restraints (OR 95%Cl 0.65; 0.31-1.37; ρ = 0.26) and the requirement of sedative agents (OR 95%Cl 0.86; 0.48-1.55; ρ = 0.62). CONCLUSIONS: In summary, the results of this meta-analysis of sixteen trials neither support nor oppose the use of melatonin in the prevention of delirium of hospitalised patients. We identified high heterogeneity across all the included trials and low certainty of evidence with potential type II error. Future multi-centre, adequately powered randomised controlled trials are warranted to provide more certainty on the use of melatonin for the prevention of delirium. PROSPERO: CRD42019123546.