Melatonin Supplements Improve Sleep in Hemodialysis Patients

Nancy A. Melville

November 22, 2010

November 22, 2010 (Denver, Colorado) — Patients undergoing dialysis who have sleep disturbances showed significant improvements in their sleep patterns with the short-term treatment of daily exogenous melatonin; however, the improvements appeared to diminish after a year, according to a study presented here at Renal Week 2010: American Society of Nephrology 43rd Annual Meeting.

Researchers in the Netherlands recently reported that kidney dialysis patients, who commonly report sleep problems, lack a natural nocturnal rise in endogenous melatonin, a hormone that plays a key role in the circadian sleep–wake rhythm.

In a double-blind placebo-controlled study that followed that study, the researchers treated 35 hemodialysis patients with daily melatonin 3 mg and another 35 patients with placebo over the course of a year. Researchers found that patients treated with melatonin showed significant improvement in sleep efficiency, actual sleep time, and actual awake time over the placebo group after 3 months.

"At 3 months, the melatonin levels among the patients in the placebo group remained the same, but in the treatment group, the patients' own melatonin rhythm improved," said lead author Marije Russcher, PharmD, from the Meander Medical Center, in Amersfoort, the Netherlands.

"At 12 months, there were no significant differences in melatonin rhythm or sleep time; however, there were improvements in the treatment group in terms of social functioning," Dr. Russcher reported.

At 3 months, the benefit of short-term use of exogenous melatonin on sleep onset latency, seen in the previous study, was confirmed (P = .023).

The improvements seen at 3 months included sleep efficiency (P = .105), actual sleep time (P = .057), and actual awake time (P = .150). At 12 months, the improvements were no longer seen. However, a trend toward improved social functioning (P = .032) and mentality (P = .094) were seen.

Noting that drugs in general often show effects in the short term but wear off in the longer term, Dr. Russcher speculated that several approaches might help improve longer-term efficacy.

"We are thinking that perhaps introducing drug holidays might help, or maybe the doses we gave were too high, and a lower dose might have a longer-term efficacy," she said. "The timing of the dose might also play a role, as might the addition of light therapy, but those are all ideas for future research," she said.

Sleep problems are exceptionally high among hemodialysis patients, with as much as 80% complaining of sleep issues, and while the problems range from restless legs syndrome to insomnia, all affect the quality of life for patients negatively.

A multitude of factors can cause sleep problems, ranging from sleep during the day in dialysis sessions to physiological aspects of the treatment itself, Dr. Russcher said.

"When you walk in our dialysis ward, I think half of the patients are sleeping during their treatment because the dialysis treatment makes them sleepy. This, of course, affects their sleep rhythm and makes it harder for them to sleep at night," she said.

"In addition, dialysis patients use a lot of medications, and those can also affect their sleep negatively."

The treatment's effect on body temperature also plays a role, she explained.

"Body temperature rises during the treatment and the body feels it has to do a cooling process, which is what normally happens at night and makes you feel sleepy. So this process also causes a lot of physiological stress."

The various factors eventually take their toll on melatonin levels.

"As kidney function declines, melatonin rhythm declines as well, and once people have impaired kidney function, melatonin levels are lower than normal," Dr. Russcher said. "With kidney disease, the levels are even lower, and by the time patients need dialysis, there's hardly any rhythm of melatonin at all anymore. This is why we feel administering melatonin might help these patients."

Although more studies are needed to better understand the role melatonin can play in helping dialysis patients, the findings are intriguing enough, and melatonin is attractive enough, to consider for patients, at least in the short term, suggested Frank C. Brosius, MD, moderator of the session and professor of internal medicine, Department of Molecular and Integrative Physiology, University of Michigan, in Ann Arbor.

"Certainly, dialysis patients have disrupted sleep patterns that at least reduce wellbeing and may enhance certain morbidities, although that's not certain," he said. "In terms of melatonin, I think the scientific underpinning for the study was valid and the trial seemed to be conducted well."

"It is reasonable to try melatonin for short periods (e.g., 3 months)," he suggested. "Longer-term treatment should be validated in their next study, but certainly this adds to the armamentarium with a low-toxicity, 'natural' compound."

Dr. Russcher and Dr. Brosius have disclosed no relevant financial relationships.

Renal Week 2010: American Society of Nephrology 43rd Annual Meeting. Abstract SA-PO2333. Presented November 20, 2010.


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