Drugs which directly counteract nitric oxide (NO), such as endothelial receptor blockers, NO-synthase inhibitors, and NO-scavengers, may be effective in the acute treatment of migraine, but are also likely to be effective in migraine prophylaxis. In the underlying pilot study the prophylactic effect of the NO scavenger hydroxocobalamin after intranasal administration in migraine was evaluated. Twenty patients, with a history of migraine of <1 year and with two to eight migraine attacks per month, were included in an open trial. A baseline period was followed by an active treatment period of 3 months with 1 mg intranasal hydroxocobalamin daily. Patients were instructed to complete a diary in which details of each attack were described. A reduction in migraine attack frequency of ≥50% was seen in 10 of 19 patients, which corresponds to 53% of the patients (responders). A reduction of ≥30% was noted in 63% of the patients. The mean attack frequency in the total study population showed a reduction from 4.7 ± 1.7 attacks per month to 2.7 ± 1.6 ( P< 0.001). For the responders the migraine attack frequency was reduced from 5.2 ± 1.9 (baseline) to 1.9 ± 1.3 attacks per month ( P < 0.005), while for those who did not respond a non-significant reduction was found: 4.1 ± 1.4 to 3.7 ± 1.5 (P > 0.1). A reduction was also observed for the total duration of the migraine attacks per month, the total number of migraine days per month and the number of medication doses for acute treatment used per month. This is the first prospective, open study indicating that intranasal hydroxocobalamin may have a prophylactic effect in migraine. As a percentage of responders in prophylactic trials of > 35-40% is unlikely to be a placebo effect, a double-blind study is warranted.
