Melatonin Agonist Cuts Delirium Risk

Caroline Cassels

February 19, 2014

Nightly administration of a melatonin agonist may help prevent delirium in older patients hospitalized for acute medical illness, new research shows.

A multicenter, randomized, placebo-controlled trial showed that ramelteon was associated with a lower risk for delirium ― 3% vs 32% ― compared with placebo.

"Ramelteon administered nightly to elderly patients admitted for acute care may provide protection against delirium. This finding supports a possible pathogenic role of melatonin neurotransmission in delirium," the authors, led by Kotaro Hatta, MD, PhD, University of Amsterdam in the Netherlands, write.

The study was published online February 19 in JAMA Psychiatry.

Heavy Burden

Independently associated with increased mortality, impaired physical and cognitive recovery, and increased healthcare costs, the estimated incidence of delirium during hospitalization in elderly patients is between 3% and 56%. Yet, at present, there is no US Food and Drug Administration (FDA)–approved medication for delirium prevention.

Several agents have been tested for delirium, and although antipsychotic agents have shown some benefit, the associated risk for adverse effects, particularly in acutely ill patients, may be cause for concern.

One previous randomized controlled trial suggested that melatonin, a pineal gland hormone that regulates the sleep-wake rhythm, is associated with a lower risk for delirium. In addition, case series have suggested that ramelteon, which was approved in 2005 by the FDA for the treatment of insomnia, may help prevent delirium in elderly patients.

To examine whether the drug may have a preventive effect, the investigators conducted the trial, which included 67 eligible patients between 65 and 89 years old.

All participants were admitted to hospital because of serious medical problems and were able to take medications orally. Patients were randomly assigned to receive ramelteon (8 mg/d, n = 33) or placebo (n = 34) every night for 7 days.

The study results revealed that ramelteon was associated with a lower risk for delirium (3% vs 32%; P = .003) with a relative risk of 0.09 (95% confidence interval [CI], 0.01 - 0.69). Even after controlling for risk factors, ramelteon was still associated with a lower incidence of delirium (P = .01; odds ratio, 0.07; 95% CI, 0.008 - 0.54).

More Research Needed

In an accompanying editorial, Sophia E. de Rooij, MD, PhD, and colleagues from the University of Amsterdam note that this study "is the first to show a significant prophylactic effect on the incidence of delirium in elderly ICU [intensive care unit] patients treated with ramelteon."

More research is needed to determine whether this strategy is effective in preventing delirium in other high-risk populations, including patients with dementia or elderly patients undergoing hip surgery.

"Other issues that remain to be addressed are the pathophysiologic mechanisms responsible for the development of delirium and the effects of melatonin and/or melatonin receptor agonists on the long-term sequelae of delirium," Dr. de Rooij and colleagues write.

The authors and editorialists report no relevant financial relationships.

JAMA Psych. Published online February 19, 2014. Abstract, Editorial

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