Cluster headache: trial of a combined histamine Hl and H2 antagonist treatment

SUMMARY Fifteen patients with symptomatic cluster headache participated in a double-blind crossover trial of a combined histamine HI and H2 antagonist treatment. The trial lasted six weeks. There was no significant improvement on active treatment as regards mean number of headache attacks per week, intensity, or duration of attacks. These results suggest that histamine does not play a significant role in the pathogenesis of cluster headache. There is evidence that histamine is implicated in the pathogenesis of cluster headache. Spontaneous attacks in some patients are associated with in-creased urinary excretion of histamine (Sjaastad and Sjaastad, 1970), and an increase in whole blood histamine (Anthony and Lance, 1971). Studies with histamine HI and H2 antagonists in the monkey have shown that the vasodilator effect of histamine on the external carotid artery is mediated predominantly by H2 receptors, whereas in the internal carotid artery both HI and H2 re-ceptors are involved (Lord et al., 1976). The prob-ability of a similar distribution of histamine receptor sites in man suggested, therefore, that if histamine is involved in the pathogenesis of cluster headache, a therapeutic effect was most likely with a combined histamine HI and H2 antagonist treatment. Patients and methods Fifteen symptomatic adult patients, aged 33-69 years (mean 49 years), suffering from cluster headache as defined by the "ad hoc " committee on the classification of headache (1962), were in-cluded in a double-blind trial. Patients were allocated to one of four treatment schedules. In two of the schedules, active treatment and placebo were crossed over at weekly intervals, whereas in the other two, each treatment was continued for two weeks at a time. Active treatment consisted of cimetidine 400 mg three times a day after meals, and 800 mg at bedtime, together with chlor-pheniramine 4 mg three times a day and 8 mg a