title: Melatonin as adjunctive therapy in the prophylaxis of cluster headache: a pilot study.
abstract: BACKGROUND
  The periodicity of cluster headache suggests involvement of the suprachiasmatic nucleus of the hypothalamus, the biological clock. The secretion of melatonin, a hormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, is altered in patients with cluster headache. Melatonin shifts circadian rhythms. A previous study of melatonin for primary prophylaxis of cluster headache demonstrated a 50% response rate.
  
  
  OBJECTIVE
  To evaluate the use of melatonin as adjunctive therapy in patients with cluster headache who have incomplete relief of their headaches on conventional therapy.
  
  
  METHODS
  Nine patients participated in the study, six with chronic cluster headache and three with episodic cluster headache. Patients with chronic cluster headache completed a baseline diary for 1 month, followed by 1 month of melatonin treatment, then 1 month of placebo. Patients with episodic cluster headache received placebo for 1 month, then melatonin for 1 month. Patients continued their usual prophylactic and abortive treatments during the study. Headache frequency, intensity, and use of analgesics were recorded. The primary endpoint of the study was the mean number of headaches per day, with mean daily analgesic consumption and percentage of mild, moderate, and severe headaches as secondary endpoints.
  
  
  RESULTS
  There were no significant differences between means on analysis of variance and t testing for the melatonin, placebo, and baseline months for all primary and secondary endpoints. There were no side effects reported.
  
  
  CONCLUSIONS
  Patients with chronic cluster headache or patients with episodic cluster headache whose headaches are uncontrolled on conventional therapy do not appear to gain therapeutically from the addition of melatonin to their usual treatment regimens. It is perhaps the phase-shifting properties of melatonin that mediate its effect in patients with episodic cluster headache, and it may be necessary to treat from the beginning of the cluster bout to reset the circadian pacemaker, thus producing a more positive outcome.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: Tamara
authors.initials: T
authors.lastname: Pringsheim
authors.forename: Eric
authors.initials: E
authors.lastname: Magnoux
authors.forename: Colin F
authors.initials: CF
authors.lastname: Dobson
authors.forename: Edith
authors.initials: E
authors.lastname: Hamel
authors.forename: Michel
authors.initials: M
authors.lastname: Aubé
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000368:Aged; D000700:Analgesics / Q000627:therapeutic use; D002908:Chronic Disease; D002940:Circadian Rhythm; D003027:Cluster Headache / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000700:Analgesics; D003692:Delayed-Action Preparations; D008550:Melatonin