title: Prophylactic activity of increasing doses of intravenous histamine in refractory migraine: Retrospective observations of a series of patients with migraine without aura.
abstract: BACKGROUND
  Histamine is thought to play a pivotal role in the modulation of peripheral and central pain. The administration of increasing doses of histamine may lead to desensitization of receptors of histamine types 1 and 2, causing meningeal vasodilation, and to depletion of neuropeptides in the trigeminal ganglion, thus inhibiting the initiation of migraine.
  
  
  OBJECTIVE
  In this study, the efficacy and tolerability of increasing doses of IV histamine in migraine prophylaxis were investigated.
  
  
  METHODS
  This single-center, open-label, retrospective, controlled study was conducted at the Headache Center (Department of Internal Medicine, University of Florence, Villa Monna Tessa, Italy). Patients included in the study had 3 to 6 migraines without aura per month that were refractory to common symptomatic and prophylactic agents in the 6 months preceding the study. Patients were treated with IV histamine hydrochloride for 21 days starting with a dosage of 0.5 mg/d and increasing to 4.0 mg/d. To assess the efficacy of the treatment, these patients were matched for age; sex; and frequency, duration, and severity of attacks with untreated migraineurs. Clinical benefit was defined as ⩽ 1 migraine of mild intensity per month. Tolerability was assessed during the hospitalization period, and patients were instructed to contact the Headache Center to report any adverse effects after hospital discharge.
  
  
  RESULTS
  The histamine group comprised 47 patients (40 women, 7 men; mean [SD] age, 42.0 [8.6] years) and the control group comprised 23 patients (20 women, 3 men; mean [SD] age, 38.8 [8.4] years). The histamine-treated patients showed a clinical benefit lasting for a mean of 10.4 (4.2) months, while the patients in the control group showed a clinical benefit of 3.8 (1.9) months. The difference in the duration of the clinical benefit between the 2 groups was 6.6 months (95% CI, 5.15-7.99). Adverse effects consisted of flushing, heat sensation during infusion, headache, and palpitations.
  
  
  CONCLUSIONS
  In this study, histamine showed lasting prophylactic efficacy in migraineurs. If further research confirms this preliminary finding, histamine could be considered when established prophylactic drugs, such as betablockers, calcium antagonists, antidepressants, and antiepileptics, have not been effective.
authors.affiliation: Headache Center, Department of Intemal Medicine, University of Florence, Villa Monna Tessa, Italy ; Department of Internal Medicine, Clinica Medica IV, Villa Monna Tessa, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Pietrini
authors.affiliation: Headache Center, Department of Intemal Medicine, University of Florence, Villa Monna Tessa, Italy ; Department of Internal Medicine, Clinica Medica IV, Villa Monna Tessa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: De Luca
authors.affiliation: Headache Center, Department of Intemal Medicine, University of Florence, Villa Monna Tessa, Italy ; Department of Internal Medicine, Clinica Medica IV, Villa Monna Tessa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Del Bene
authors.affiliation: Headache Center, Department of Intemal Medicine, University of Florence, Villa Monna Tessa, Italy ; Department of Internal Medicine, Clinica Medica IV, Villa Monna Tessa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Cesaris
authors.affiliation: Department of Internal Medicine, Clinica Medica IV, Villa Monna Tessa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bertinotti
authors.affiliation: Department of Internal Medicine, Clinica Medica IV, Villa Monna Tessa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Colangelo
authors.affiliation: Department of Internal Medicine, Clinica Medica IV, Villa Monna Tessa, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Moggi Pignone
keywords: histamine; migraine; prophylaxis