Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy

Abstract

Purpose Melatonin, which is produced by the pineal gland at night, is an endogenous sleep regulator. Both sleep disorders and impaired melatonin production are common among the elderly. We examined the excretion of the major melatonin metabolite 6-sulfatoxymelatonin in insomnia patients aged ≥55 years and its relation with the subsequent response to melatonin therapy. Methods We studied 517 insomnia patients, along with 29 age-matched and 30 younger healthy volunteers. Nocturnal urinary 6-sulfatoxymelatonin excretion was assessed between 10 pm and 10 am. Three hundred and ninety-six of the insomnia patients were treated for 2 weeks with placebo and for 3 weeks with 2 mg per night of controlled-release melatonin, of which 372 provided complete datasets. Clinical response, assessed with the Leeds Sleep Evaluation Questionnaire, was defined as an improvement of 10 mm or more on the visual analog scales. Results Mean (± SD) 6-sulfatoxymelatonin excretion was lower in the insomnia patients (9.0 ± 8.3 μg per night) than in volunteers of the same age (18.1 ± 12.7 μg per night, P <0.05) and in younger volunteers (24.2 ± 11.9 μg per night, P <0.05). About 30% of patients (112/372) excreted ≤3.5 μg of sulfatoxymelatonin per night, which is considered to be lower than normal for this age group. These “low excretors” had a significantly higher response to melatonin replacement therapy (58% [65/112] vs. 47% [122/260], P <0.05). Conclusion Low nocturnal melatonin production is associated with insomnia in patients aged 55 years or older, and identifies patients who are somewhat more likely to respond to melatonin replacement.