Warfarin as a therapeutic option in the control of chronic cluster headache: a report of three cases

Abstract

IntroductionCluster headache is perhaps the best defined trigeminal autonomic cephalalgia. Its less frequent form, chronic cluster headache, frequently eludes available medical therapies [1]. Three cases of chronic cluster headaches that were responsive to oral anticoagulation are described. The paucity of effective therapies to treat this condition [1,2], and the puzzling effectiveness of warfarin in the cases described here, justify reporting of this uncontrolled evidence. Case reports Patient 1A 46-year-old white male presented with cluster headache since the age of 32 years, and with chronic cluster headache since the age of 35 years. He was submitted to currently available prophylactic therapies for cluster headache such as prednisone, deflazacort, verapamil, lithium carbonate, methysergide, divalproate, pizotifen, lamotrigine and topiramate, and to several other unconventional therapeutic drugs. He only responded to steroids, which produced a partial and transitory response. He took prednisone for a prolonged period, which may have contributed to the chronification of his cluster headache. A retrogasserian balloon compression led to a transitory remission. In September 2003, after an earlier communication of the case subsequently described by Souza et al. [3], warfarin 2.5 mg/day up to 10 mg/day was prescribed. Cluster headache attacks decreased during the titration period and were followed by a sustained remission in the succeeding two months, allowing him to discontinue prednisone. The attacks recurred when warfarin was withdrawn, but their frequency and intensity decreased again from 6 daily full-blown episodes to a headache-free condition after two mild episodes following J Headache Pain (2005) 6:417-419 DOI 10.1007/s10194-005-0234-6Warfarin as a therapeutic option in the control of chronic cluster headache: a report of three cases Abstract Chronic cluster headache remains refractory to medical therapy in at least 30% of those who suffer from this condition. The lack of alternative medical therapies that are as effective as, or more effective than, lithium carbonate makes new therapies necessary for this highly disabling condition. Based on a previous report, we gave oral anticoagulants to three patients with chronic cluster headache. Two of them remained cluster headachefree while taking warfarin. In the third patient, the use of warfarin for three weeks initially increased the frequency and intensity of cluster headache attacks but subsequently induced a prolonged remission. In spite of the paucity of data available, oral anticoagulation appears to be a promising therapy for chronic cluster headache.

Treatment of Cluster Headache: The American Headache Society Evidence‐Based Guidelines

“…Warfarin is the only medication that has been administered a new positive recommendation (Level C). The rationale for studying this treatment for CH was derived from anecdotal reports of incidental CH benefit in patients taking warfarin for other indications . The study author hypothesized that the potential benefit of warfarin in CH treatment relates to the impact of vitamin K antagonism on dendritic and neuronal metabolism, circadian rhythms of the hypothalamus, and nitric oxide mediated neurogenic inflammation.…”

“…The rationale for studying this treatment for CH 12 was derived from anecdotal reports of incidental CH benefit in patients taking warfarin for other indications. 24,25 The study author hypothesized that the potential benefit of warfarin in CH treatment relates to the impact of vitamin K antagonism on dendritic and neuronal metabolism, circadian rhythms of the hypothalamus, and nitric oxide mediated neurogenic inflammation. We agree with the study conclusions of the author, who advocated for larger RCTs that would further elucidate the possible efficacy of warfarin for treating CH, and if effective, would help to determine the optimal level and duration of anticoagulation.…”

Warfarin for Refractory Chronic Cluster Headache: A Randomized Pilot Study

“…Few case reports have described the induction of remission in patients with refractory CCH upon institution of warfarin therapy 12,13 . Similar case reports on the efficacy of warfarin 14,15 or acenocoumarol 16 in patients with migraine do exist.…”

“…There have been isolated case reports on induction of remission in patients with CCH refractory to pharmacological treatment upon institution of oral anticoagulant therapy 12,13 . Similar reports on the efficacy of oral anticoagulants in migraineurs do exist 14‐17 .…”

Recommandations pour le diagnostic et le traitement de l’algie vasculaire de la face

“…Après la description de l'efficacité de la warfarine [124] dans une observation clinique, un essai en double insu contre placebo a confirmé l'efficacité de la warfarine dans la forme chronique réfractaire de l'AVF (grade B) [125]. La mélatonine a eu une efficacité modeste dans une étude pilote en double insu chez des patients avec une forme épisodique d'AVF [126], les résultats étant négatifs dans la forme chronique [126,127].…”