title: Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention.
abstract: BACKGROUND
  Melatonin has been studied in headache disorders. Amitriptyline is efficacious for migraine prevention, but its unfavourable side effect profile limits its use.
  
  
  METHODS
  A randomised, double-blind, placebo-controlled study was carried out. Men and women, aged 18-65 years, with migraine with or without aura, experiencing 2-8 attacks per month, were enrolled. After a 4-week baseline phase, 196 participants were randomised to placebo, amitriptyline 25 mg or melatonin 3 mg, and 178 took a study medication and were followed for 3 months (12 weeks). The primary outcome was the number of migraine headache days per month at baseline versus last month. Secondary end points were responder rate, migraine intensity, duration and analgesic use. Tolerability was also compared between groups.
  
  
  RESULTS
  Mean headache frequency reduction was 2.7 migraine headache days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo. Melatonin significantly reduced headache frequency compared with placebo (p=0.009), but not to amitriptyline (p=0.19). Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency. Melatonin was better tolerated than amitriptyline. Weight loss was found in the melatonin group, a slight weight gain in placebo and significantly for amitriptyline users.
  
  
  CONCLUSIONS
  Melatonin 3 mg is better than placebo for migraine prevention, more tolerable than amitriptyline and as effective as amitriptyline 25 mg.
authors.affiliation: Albert Einstein Hospital, São Paulo, Brazil Department of Neurology, UNIFESP, São Paulo, Brazil.
authors.forename: Andre Leite
authors.initials: AL
authors.lastname: Gonçalves
authors.affiliation: Albert Einstein Hospital, São Paulo, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Martini Ferreira
authors.affiliation: Department of Neurology, UNIFESP, São Paulo, Brazil Neurology Department, FMABC, Santo Andre, Brazil.
authors.forename: Reinaldo Teixeira
authors.initials: RT
authors.lastname: Ribeiro
authors.affiliation: Albert Einstein Hospital, São Paulo, Brazil.
authors.forename: Eliova
authors.initials: E
authors.lastname: Zukerman
authors.affiliation: Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Cipolla-Neto
authors.affiliation: Albert Einstein Hospital, São Paulo, Brazil.
authors.forename: Mario Fernando Prieto
authors.initials: MF
authors.lastname: Peres
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D008881:Migraine Disorders / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000639:Amitriptyline; D008550:Melatonin
keywords: MIGRAINE