BACKGROUND
Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders.
This study aims to determine the effect of oral Melatonin 5mg immediate release (IR) nightly for 5 nights on severity of delirium in older (≥65 years) medical inpatients.
METHODS
This was a double blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital.
Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 hours of admission or onset of in-hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS).
RESULTS
120 were randomized, 61 to Melatonin 5mg and 59 to Placebo. The medication was well tolerated. The mean MDAS was -4.85 (S.D. 7.56) in the Melatonin group and -5.35 (S.D. 7.23) in the Placebo group, p-value 0.42, a non-significant difference. A post-hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [IQR 4,12] vs Placebo group 10 [IQR 6,16] p-value =0.033, Wilcoxon Rank Sum test).
CONCLUSIONS
This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied.