Melatonin Cuts ICU Delirium Risk by 28% and Shortens Hospital Stays

Melatonin is best known as a sleep hormone, but it also regulates circadian rhythms, modulates immune function, and acts as a potent antioxidant. In the ICU, these systems are critically disrupted — and so is melatonin itself. Studies have consistently shown that critically ill patients produce far less endogenous melatonin than healthy individuals, raising the question of whether supplementation could meaningfully improve outcomes.

This systematic review and meta-analysis pooled data from 32 randomized controlled trials enrolling 3,895 adult ICU patients. Researchers compared melatonin supplementation against no melatonin across a range of patient-centered outcomes, applying the GRADE framework to assess certainty of evidence.

The headline result: melatonin reduced the risk of delirium by 28% (RR 0.72; 95% CI, 0.58–0.89). It also modestly shortened ICU length of stay by about half a day and improved perceived sleep quality. Importantly, melatonin did not increase adverse events — a meaningful safety signal given concerns about sedation and immune suppression in fragile patients.

However, the evidence was rated low certainty across most outcomes, downgraded due to significant risk of bias in included trials and inconsistency in results. Outcomes including anxiety, agitation, PTSD incidence, sleep awakenings, ICU mortality, and post-ICU functional status remained uncertain at very low to low certainty levels.

For longevity-minded readers, this research highlights how circadian rhythm disruption — a hallmark of aging and critical illness alike — may be partially addressable with a widely available, low-cost supplement. The findings reinforce melatonin's multi-system role beyond sleep. Still, clinicians should await higher-certainty evidence before standardizing ICU melatonin protocols, and future trials must clarify optimal dose, timing, and which patient subgroups benefit most.