Recovery of circadian melatonin rhythm after a melatonin holiday in daytime haemodialysis patients on long-term exogenous melatonin.

The effects of exogenous melatonin on sleep diminish after its long-term use in haemodialysis patients. Our aim was to determine whether melatonin levels accumulate after chronic (at least three months) use of exogenous melatonin, 5 mg daily, and whether discontinuation of this treatment improves endogenous melatonin production and improves the circadian sleep-wake rhythm. In this case series, stable haemodialysis patients discontinued their chronic exogenous melatonin usage for seven days and melatonin concentrations in saliva were analysed. The primary endpoint was recovery of a normal circadian melatonin rhythm. Secondary endpoints were the effects on melatonin pharmacokinetics and sleep parameters. At day three after discontinuation the normal circadian melatonin rhythm recovered in the two patients who discontinued the treatment for the full week. They also had an effective maximum trough level of melatonin. Discontinuing melatonin seems to result in recovery of the circadian rhythm, based on achievement of effective melatonin thresholds. Further research is necessary to investigate whether sleep parameters improve after a drug holiday.most appropriate treatment.