Results from a double blinded, randomised, placebo-controlled, feasibility trial of melatonin for the treatment of delirium in older medical inpatients

BACKGROUND: Delirium is common in elderly inpatients, causing distress, cognitive decline and death. No known intervention improves the course of delirium; current treatments are symptomatic, and limited by lack of efficacy and adverse effects. There is an urgent need to find an effective treatment for delirium. AIMS: To determine the feasibility of a trial of oral melatonin 5 mg nightly for five nights for the treatment of delirium in older medical inpatients, and determine the participants required to demonstrate a clinically and statistically significant decrease in severity of delirium in older medical inpatients treated with melatonin. METHODS: This was a double blinded, randomised controlled trial in general internal medicine units of a tertiary teaching hospital. Older (≥70 years) inpatients with confusion assessment method positive hyperactive or mixed delirium were suitable for inclusion. Subjects received melatonin 5 mg oral nightly for five nights or matching placebo. The primary outcome was the Memorial Delirium Assessment Scale (MDAS) administered daily. RESULTS: No adverse effects occurred due to melatonin. In the treatment group, the mean change in MDAS from baseline during treatment period was 2.5 ± 5.0 points, in the placebo group, 2.1 ± 4.1 points, a non-significant difference. A power calculation accounting for drop-out (31.0%), suggests 120 participants would be required to demonstrate with 90% power that melatonin 5 mg reduces the severity of delirium by 3 points or more on MDAS. CONCLUSIONS: A trial of the hypothesis that 5 mg melatonin nightly for five nights reduces delirium severity in older medical inpatients would require 120 patients, and is feasible