Urinary 6-sulphatoxymelatonin levels are depressed in chronic migraine and several comorbidities

Headache. 2010 Mar;50(3):413-9. doi: 10.1111/j.1526-4610.2009.01547.x. Epub 2009 Oct 8.


Objective: To assess urinary 6-sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls.

Background: Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders.

Methods: Urine samples were collected into a single plastic container over a 12-hour period from 8:00 pm to 8:00 am of the next day, and 6-sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory.

Results: A total of 220 subjects were evaluated - 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6-sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6-sulphatoxymelatonin levels and depression, anxiety, and fatigue.

Conclusions: To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anxiety Disorders / epidemiology
  • Anxiety Disorders / physiopathology
  • Anxiety Disorders / urine
  • Biomarkers / analysis
  • Biomarkers / urine
  • Comorbidity
  • Depressive Disorder / epidemiology
  • Depressive Disorder / physiopathology
  • Depressive Disorder / urine
  • Down-Regulation / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Fatigue Syndrome, Chronic / epidemiology
  • Fatigue Syndrome, Chronic / physiopathology
  • Fatigue Syndrome, Chronic / urine
  • Female
  • Fibromyalgia / epidemiology
  • Fibromyalgia / physiopathology
  • Fibromyalgia / urine
  • Humans
  • Male
  • Melatonin / analogs & derivatives*
  • Melatonin / analysis
  • Melatonin / metabolism*
  • Melatonin / urine
  • Middle Aged
  • Migraine Disorders / epidemiology*
  • Migraine Disorders / physiopathology
  • Migraine Disorders / urine*
  • Mood Disorders / epidemiology*
  • Mood Disorders / physiopathology
  • Mood Disorders / urine*
  • Neuropsychological Tests
  • Predictive Value of Tests
  • Prevalence
  • Sleep Initiation and Maintenance Disorders / epidemiology
  • Sleep Initiation and Maintenance Disorders / physiopathology
  • Sleep Initiation and Maintenance Disorders / urine
  • Surveys and Questionnaires
  • Young Adult


  • Biomarkers
  • 6-sulfatoxymelatonin
  • Melatonin