Melatonin decreases delirium in elderly patients: A randomized, placebo-controlled trial

Background: Disturbance in the metabolism of tryptophan and tryptophan-derived compounds (e.g., melatonin) may have a role in the pathogenesis of delirium. Objective: To evaluate the efficacy of low dose exogenous melatonin in decreasing delirium. Design: A randomized, double-blinded, placebo-controlled study. Setting: An Internal Medicine service in a tertiary care centre in London, Ontario, Canada. Participants: 145 individuals aged 65 years or over admitted through the emergency department to a medical unit in a tertiary care hospital. Intervention: Patients were randomized to receive either 0.5 mg of melatonin or placebo every night for 14 days or until discharge. Measurements: The primary outcome was the occurrence of delirium as determined by Confusion Assessment Method (CAM) criteria. Results: Of a total of 145 individuals (mean age (standard deviation): 84.5 (6.1) years) 72 were randomly assigned to the melatonin group and 73 to the placebo group. Melatonin was associated with a lower risk of delirium (12.0% vs. 31.0%, p=0.014), with an odds ratio (OR), adjusted for dementia and comorbidities of 0.19 (95% confidence intervals (CI): 0.06-0.62). Results were not different when patients with prevalent delirium were excluded. Limitation: An intention to treat analysis was not possible due to loss to follow-up. Conclusion: Exogenous low dose melatonin administered nightly to elderly patients admitted to acute care may represent a potential protective agent against delirium.