Melatonin, a commonly used over-the-counter sleep aid, reduced the incidence of postoperative delirium in people over 60 years of age according to the results of a systematic review and meta-analysis of clinical trials.¹ While melatonin was concluded to be successful at lowering postoperative delirium compared to controls, ramelteon, a prescription drug that mimics melatonin by binding to melatonin's receptors, showed no similar benefit.

Postoperative delirium is a disturbance in cognition which includes altered attention and awareness that develops after surgery. It has been estimated to affect up to 74% of older individuals following surgery and is associated with an increased risk of mortality or illness, longer hospital stays, and greater healthcare costs. Circadian sleep-wake cycle disturbances observed in people with postoperative delirium have led to the premise that melatonin, a sleep-inducing hormone produced in the body in response to darkness, could be of benefit. Synthesis of the hormone by the brain's pineal gland has been found to be reduced in association with anesthesia and surgery.

The meta-analysis included 12 randomized, controlled trials that evaluated the potential benefit of melatonin plus four trials that examined the use of the melatonin mimetic ramelteon for the prevention of postoperative delirium. The trials included a total of 1,788 men and women over the age of 60 years, among whom 48.7% received melatonin or ramelteon and the remainder were part of the control groups.

Delirium incidence among participants who were given melatonin was reduced by 33% compared with control group participants, but was not significantly reduced, compared to controls, among participants who received ramelteon. When the researchers examined the effects of higher melatonin doses of at least 5 milligrams, the risk of delirium was reduced by 48% compared with the controls.

"Perioperative administration of melatonergic agents—particularly melatonin—was associated with reduced postoperative delirium among elderly surgical patients," the authors concluded. "Future research should include adequately powered, multicenter randomized controlled trials designed to compare melatonin and ramelteon directly, explore mechanistic biomarkers of neuroinflammation and sleep-wake regulation, and evaluate broader postoperative outcomes such as pain, recovery profiles, and functional cognition."