Use of High Sumatriptan Dosages During Episodic Cluster Headache: Three Clinical Cases

Abstract

The authors describe three patients with episodic cluster headache whose attacks were all treated with subcutaneous sumatriptan.The patients described had a high frequency of attacks (more than two per day); therefore, far higher dosage of the drug was taken than commonly used in cluster headache. The patients did not experience any particular side effects, neither during the treatment period nor on abrupt withdrawal of the drug. Moreover, neither tachyphylaxis nor addiction were observed.The authors point out both the efficacy of sumatriptan, confirmed in all the treated attacks, and its safety even at higher dosages than recommended.Key words: episodic cluster headache, sumatriptan, side effects (Headache 1996;36:389-391) The lack of reliable models by which to interpret the different pathophysiologic events underlying migraine and cluster headache makes the definitive pharmacological therapy, either preventive or symptomatic, of these diseases a yet unresolved issue. Sumatriptan, with a chemical structure very similar to serotonin, is a specific and highly selective agonist at 5HT1-like receptors located in the trigeminal nerve endings which are correlated to vascular and meningeal structures sensitive to pain. It is also active on serotonin receptors found on the intracranial blood vessels, thus selectively constricting the major arteries. Sumatriptan's mechanism of action is also believed to implicate an inhibition of the neuropeptide-mediated neurogenic inflammation of the extracranial and meningeal blood vessels. In fact, it seems to inhibit the release of calcitonin gene-related peptide. [1][2][3][4][5][6] The high selectivity of this molecule explains the fact that it does not alter flow resistance of the coronary and peripheral vessels 7 unlike, for example, ergotamine. [8][9] At present, sumatriptan is available in Italy as 100-mg tablets and as preloaded syringes containing 6 mg for subcutaneous administration by an autoinjector device. In other countries, the oral preparation is available as 25-mg and 50-mg tablets.

Alteration in Nature of Cluster Headache During Subcutaneous Administration of Sumatriptan

“…9 Similar results were seen in 138 patients participating in the Cluster Headache Long-Term Study Group, which treated a total of 6353 attacks over 3 months. 10 No side effects were found in Centonze's three patients who were treated for at least three attacks a day for up to 4 months with sumatriptan, 6 mg, for each attack, 11 while Gobel et al, 12 in a 1-year long-term study of 52 patients, reported sumatriptan side effects but no alteration in the nature of the CH of the type found in our series.…”

“… 7 Studies of the efficacy and adverse effects of long‐term treatment with sumatriptan in CH are limited and report conflicting findings. 8–12 …”

“…7 Studies of the efficacy and adverse effects of longterm treatment with sumatriptan in CH are limited and report conflicting findings. [8][9][10][11][12] This study describes four episodic CH patients treated with the drug for the first time who developed a dramatic increase in the frequency of their attacks. Three also developed a change in the nature of the headache and two experienced prolongation of the CH period.…”

Cluster Headache: Opportunities for Pharmacists to Improve Care

“…Another case report observed 3 individuals with CH over 1 year, all of whom experienced 3 to 4 attacks daily and administered SC SM 6 mg for each attack. 35 Per the authors, “none of the patients showed any side effect, not even of a minor nature.” No electrocardiograph or blood pressure value alterations were detected. Regarding efficacy, the authors stated, “the efficacy of the final dose of sumatriptan for each of the 3 patients was equivalent to that observed at the beginning of the cluster.” An open, prospective study examined 52 patients with CH and cumulatively treated 2,031 attacks over the 1-year study period.…”

Cluster headache

“…Sumatriptan, 6 mg subcutaneously, was effective in 88% of the attacks, with 57% of patients becoming pain free within 15 minutes [12•, Class III]. Centonze et al [21] describe three patients who treated three or more attacks per day during bouts lasting 2 to 4 months, for a total of 166 to 278 attacks. The drug was well tolerated in these high doses.…”