Long‐term effects of melatonin on quality of life and sleep in haemodialysis patients (Melody study): a randomized controlled trial

Abstract

AIMThe disturbed circadian rhythm in haemodialysis patients results in perturbed sleep. Short term melatonin supplementation has alleviated these sleep problems. Our aim was to investigate the effects of long-term melatonin supplementation on quality of life and sleep. METHODSIn this randomized double-blind placebo-controlled trial haemodialysis patients suffering from subjective sleep problems received melatonin 3 mg day -1 vs. placebo during 12 months. The primary endpoint quality of life parameter 'vitality' was measured with Medical Outcomes Study Short Form-36. Secondary outcomes were improvement of three sleep parameters measured by actigraphy and nighttime salivary melatonin concentrations. RESULTSSixty-seven patients were randomized. Forty-two patients completed the trial. With melatonin, no beneficial effect on vitality was seen. Other quality of life parameters showed both advantageous and disadvantageous effects of melatonin. Considering sleep, at 3 months sleep efficiency and actual sleep time had improved with melatonin compared with placebo on haemodialysis days (difference 7.6%, 95% CI 0.77, 14.4 and 49 min, 95% CI 2.1, 95.9, respectively). At 12 months none of the sleep parameters differed significantly from placebo. Melatonin salivary concentrations at 6 months had significantly increased in the melatonin group compared with the placebo group. CONCLUSIONSThe high drop-out rate limits the strength of our conclusions. However, although a previous study reported beneficial short term effects of melatonin on sleep in haemodialysis patients, in this long-term study the positive effects disappeared during follow up (6-12 months). Also the quality of life parameter, vitality, did not improve. Efforts should be made to elucidate the mechanism responsible for the loss of effect with chronic use.

The Effects of Kidney Transplantation on Sleep, Melatonin, Circadian Rhythm and Quality of Life in Kidney Transplant Recipients and Living Donors

“…As a result, we observed only a small, non-significant difference in mean melatonin concentrations and AUCs between donors and recipients, whereas we had expected much lower melatonin concentrations in KTR than in LD based on our earlier findings in hemodialysis patients [15] and recent findings [unpublished data]. In our study, the timing of saliva sampling may have played a role since the nocturnal melatonin peak is expected to occur between 2:00 and 4:00.…”

“…We did not take samples at these times not wanting to create discomfort to the patients. Possibly, the melatonin peak differences between donors and acceptors would have been larger if nightly samples had been collected between 2 and 4 a.m. [12,13,15,23,35]. …”

“…Its increase in the evening correlates with sleep propensity and onset of sleep [9,10,11]. In ESRD not only do sleep disturbances frequently occur, but nocturnal melatonin levels are also reduced [12,13,14,15]. Even though sleep disturbances in renal patients are well recognized clinically, little attention is paid to their possible linkage with lowered melatonin levels or perturbed functioning of the circadian clock.…”

Sleep Disorders, Restless Legs Syndrome, and Uremic Pruritus: Diagnosis and Treatment of Common Symptoms in Dialysis Patients

“…Although shown to be effective in dialysis patients in the short term, a study of 67 maintenance HD patients randomly assigned to receive melatonin (3 mg, immediate release) versus placebo for 1 year did not show an improvement in sleep parameters over the longer time frame. 22 …”

What to eat for a better sleep in haemodialysis patients: Potential role of B vitamins intake and appetite

“…Circadian rhythm deteriorates in HD patients because melatonin secretion, which plays the crucial role in biological clock and circadian sleep-wake rhythms and in the onset of the sleep in evenings, decreases when the kidney functions decline. Moreover, nocturnal melatonin secretion was reported to be absent in HD patients 4. Uremic restless leg syndrome (URL-Synd) negatively affects sleep.…”