Dear Editor,
We read with interest the randomized controlled trial comparing 3 and 6 mg prophylactic melatonin for the prevention of intensive care unit (ICU) delirium. The study addresses an important question, and we commend the authors for their work in this area. We would like to offer three brief concerns before the findings are interpreted as practice-changing.1
First, there appears to be a baseline age imbalance despite randomization, with the 6 mg group being older than the 3 mg group. Since age is an established risk factor for delirium, this may have influenced the results and makes simple unadjusted comparisons less robust.2
Second, the analysis did not appear to account for several important ICU-related confounders, including illness severity, sedative and analgesic exposure, mechanical ventilation status, and evolving organ dysfunction. Given the multifactorial nature of delirium, adjustment for these variables would have strengthened the interpretation that the observed benefit was truly attributable to melatonin dose.2
Third, delirium assessment may not have captured all episodes. Although confusion assessment method for the intensive care unit (CAM-ICU) was performed twice daily, delirium is often fluctuating and may have been missed between assessments. In addition, because melatonin was given at night and CAM-ICU scoring was done at the same time, the timing of assessment may have affected the detection of delirium. As a result, it is unclear whether the observed reduction was due to the drug itself, the assessment schedule, or both.
In summary, this trial provides useful preliminary insight into a possible dose-response effect of melatonin.3,4 The findings should be interpreted cautiously in light of the age imbalance, unadjusted confounders, and the possibility of incomplete delirium ascertainment. Further multicenter studies with standardized assessment, appropriate adjustment for confounding, and intention-to-treat analysis would help clarify the role of 6 mg melatonin in delirium prophylaxis.
Orcid
Nishanth Baliga https://orcid.org/0000-0002-6401-0887
Footnotes
Source of support: Nil
Conflict of interest: None
References
- 1.Kumar PA, Chawla K, Kohli S, Singh R. Comparison of two doses of prophylactic melatonin on incidence of delirium in intensive care unit patients: A randomized controlled trial. Indian J Crit Care Med. 2026;30(4):319–323. doi: 10.5005/jp-journals-10071-25187. [DOI] [PMC free article] [PubMed] [Google Scholar]
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