Melatonin Studied for Prevention Of Delirium in Elderly Patients

Delirium is a state of disturbed consciousness that often afflicts elderly, hospitalized patients and is associated with risks such as dementia or death. There is no Food and Drug Administration (FDA) approved medication for preventing it.

Studies have suggested that low levels of the pineal hormone melatonin might play a role in delirium. Indeed, low melatonin concentrations have been linked with delirium, and melatonin levels tend to decline considerably with aging. One study of this hypothesis, reported in 2011 in the International Journal of Geriatric Psychiatry, was conducted by Tareef Al-Aama, M.D., an internist and geriatrician at King Abdulaziz University in Saudi Arabia, and Canadian colleagues. Their randomized, double-blind, placebo-controlled study of elderly hospitalized patients suggested that melatonin might help prevent delirium. Only 12 percent of their study group getting melatonin experienced delirium, whereas 31 percent of a placebo group did—a significant difference.

Now Kotaro Hatta, M.D., Ph.D., a psychiatrist at Juntendo University in Japan, and coworkers have conducted a randomized, rater-blinded, placebo-controlled study of 67 older hospitalized patients to see whether a melatonin agonist called ramelteon might be able to prevent delirium.

Their results were encouraging. Only 3 percent of subjects getting ramelteon developed delirium, while 32 percent of subjects receiving a placebo did—a significant difference. These findings were published online February 19 in JAMA Psychiatry.

“This is an interesting study despite the small size of the sample,” Gary Kennedy, M.D., a professor of psychiatry at Albert Einstein College of Medicine and director of the Division of Geriatric Psychiatry at Montefiore Medical Center, told Psychiatric News. “It reinforces the novel theory that melatonin is involved in the genesis of delirium and would explain in part why older adults are more likely to develop delirium. The potential of Ramelteon to reduce the risk of delirium is especially appealing because of its low profile of adverse reactions, unlike the antipsychotics that are so often used when delirious behavior threatens the patient’s well-being.”

“Delirium is a common condition among the elderly patients who are admitted to hospitals, with profound and devastating effects on patients, families, health care systems, and society,” Al-Aama told Psychiatric News. “It’s quite frustrating that it remains poorly understood in spite of advancement in research and medical knowledge. There has been more interest lately in looking for a role for melatonin disturbance in the formation and therefore the prevention and treatment of delirium, in a ‘thinking outside the box’ kind of way. This study adds to the body of evidence that melatonin may indeed have a role in delirium. Melatonin and melatonin agonists are appealing as they tend to be reasonably safe and not so expensive. More and larger studies may be needed to confirm its role. But for now, we do seem to be moving in the right direction in fighting delirium.”

Ramelteon has been approved by the FDA for treating insomnia, Hatta and his team noted, but whether its sleep-promoting ability is related to its delirium-preventing ability is unclear, they said.

The study by Hatta and his group was funded by the Japan Society for the Promotion of Science. ■