Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study

Eur Neurol. 2008;59(5):237-42. doi: 10.1159/000115637. Epub 2008 Feb 8.


Background: Histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology.

Objective: To evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate.

Methods: Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment.

Results: The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%).

Conclusion: The present study provides evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis. Subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Double-Blind Method
  • Female
  • Fructose / administration & dosage
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Histamine / administration & dosage*
  • Histamine / adverse effects
  • Histamine Agonists / administration & dosage*
  • Histamine Agonists / adverse effects
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Migraine Disorders / prevention & control*
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / adverse effects
  • Topiramate


  • Histamine Agonists
  • Neuroprotective Agents
  • Topiramate
  • Fructose
  • Histamine