Comparison of Two Doses of Prophylactic Melatonin on Incidence of Delirium in Intensive Care Unit Patients: A Randomized Controlled Trial

Background and aims: Delirium is a frequent and serious complication in critically ill patients, contributing to prolonged mechanical ventilation, extended intensive care unit (ICU) stays, and increased mortality.Disruption of circadian rhythms plays a key role in its pathogenesis.Melatonin, a neurohormone with chronobiotic and antioxidant properties, may help prevent ICU delirium, though the optimal dose remains uncertain.Patients and methods: This prospective, randomized, interventional study enrolled 120 adult ICU patients, randomized to receive either 3 mg (group A) or 6 mg (group B) oral melatonin nightly for at least 5 days.Baseline parameters were comparable between groups.Delirium incidence was assessed twice daily using the confusion assessment method for the ICU (CAM-ICU).Secondary outcomes included the timing of delirium onset, adverse effects, ICU stay, and mortality.Results: Delirium occurred in 55.0% of patients in group A and 36.7% in group B ( = 4.062, p = 0.044), indicating a significant reduction with 6 mg of melatonin.The mean (SD) day of delirium onset and ICU length of stay were comparable between groups.Daytime somnolence was mild and similar across groups.Conclusions: Prophylactic administration of 6 mg of oral melatonin significantly reduced ICU delirium incidence compared with 3 mg, without added adverse effects.Higher-dose melatonin appears safe and more effective for delirium prevention in critically ill adults.