Ergots were the earliest effective therapy, although they have been largely supplanted by newer agents (3). Horton demonstrated that intravenous ergotamine tartrate 0.2 to 0.3 mg rapidly terminated attacks of cluster headache (15). Horton and others also studied the use of ergotamine tartrate 1 mg and caffeine 100 mg (17). Two tablets at attack onset was the effective dose. Unfortunately, the oral route of administration does not work rapidly or reliably enough. Taking this drug sublingually or by inhalation can be highly effective, when available (20,40). Suppositories of ergotamine and caffeine have been utilized, but again are generally not fast enough, although some have used oral and rectal ergotamine as prophylaxis (36).

Dihydroergotamine mesylate 0.5 to 1 mg intravenously, preceded by 10 mg metoclopramide intravenously rapidly terminates attacks of cluster headache. Benefit occurs in less than 15 minutes (26). This strategy is most appropriate for the office or emergency room. Dihydroergotamine may also be self-administered subcutaneously or intramuscularly at 1 mg two to three times daily, although these routes do not provide relief as quickly. Intranasal dihydroergotamine as reported does not work fast enough to shorten individual attacks, but may lessen their severity (1). The optimal dose by this route is unclear and 2 mg administered intranasally might be effective (39). Personal observations on the use of a compounded 2 mg suppository suggest too slow an onset of action to be a therapeutic consideration given the variety of options available (43).

Ergots have effects at many receptors, including 5-HT_1D/1B. They are known to suppress neurogenic inflammation and prevent the release of inflammatory neuropeptides, including CGRP (24). The side effects of ergots are well known and limit their usefulness in treating cluster headache. They are vasoconstrictors and therefore should be avoided in patients with coronary artery disease, vasospastic angina, Raynaud disease, and other vascular diseases. They are also contraindicated in uncontrolled hypertension and pregnancy. Concomitant use with other vasoconstrictors such as methysergide and triptans should be avoided. Limitations on ergotamine dosing to 6 mg per day and 10 mg per week have been advocated to avoid ergotism, although other parameters are sometimes utilized (36). There are also limitations on dihydroergotamine use (≤3 mg per day), although this drug may be better tolerated. Nausea can be treated with antiemetics, and leg
cramps respond to dose reduction. Diarrhea usually responds to diphenoxylate and atropine, or loperamide.

Inhalation of oxygen as a cluster treatment has a number of desirable features. Unlike ergotamine, it is not contraindicated in the presence of coronary artery disease. When used correctly, it is rapidly effective, and can be administered multiple times a day. Like ergotamine tartrate, its use in this condition was first advocated by Horton at the Mayo Clinic (16). Kudrow reported that when used properly, between 70% and 80% of patients respond within 15 minutes, making it an ideal therapy (21). The efficacy of inhaled oxygen has been confirmed in a double-blind study (9). The mechanism of action is unclear. Oxidation of nitric oxide, the putative final common mediator of “vascular” headache is one possibility, resulting in vasoconstriction. Oxygen may suppress neurogenic inflammation. Ultimately, why oxygen is effective is not known (18). Hyperbaric oxygen therapy has been studied in cluster headaches both as acute therapy and as a preventive agent (5,31). At present, the results are contradictory. Benefit may actually be a result of either the hyperbaric condition or a significant placebo effect (32). In any event, it does not seem to offer any advantage over routine oxygen treatment (see below). Even if it were shown to be effective, the lack of hyperbaric chambers and the amount of time required to perform such treatments make them of theoretical interest only.

Many patients use more than one type of oxygen tank, typically a larger tank at the bedside for nocturnal attacks, and a smaller portable tank to take in their car and for the office. During a headache, 100% oxygen at at least 7 L/min by face mask is inhaled. The patient should sit upright, lean slightly forward, and breathe deeply, but not rapidly. Most patients respond well, although some report oxygen use merely delays the headache attack, rather than eradicating it.

A recent report suggests that high-flow oxygen therapy (15 L/min) may be effective in those unresponsive to lower flow rates (35) (Table 95-1).

The introduction of sumatriptan to the market was a real revolution in cluster headache treatment, and subcutaneous sumatriptan 6 mg can currently be considered the most effective drug for the management of the cluster headache attack.

The clinical response to subcutaneous sumatriptan appears to be greater and more rapid in cluster headache compared with migraine patients, and the drug is also better tolerated in cluster headache.

Headache relief was obtained in 96% of cluster headache cases at 15 minutes (7,8). The efficacy of subcutaneous sumatriptan was reported to be approximately 8% less in patients with chronic as opposed to episodic cluster headache (12). Given the short duration and severity of the attacks, rapidity of action is a crucial factor. Subcutaneous sumatriptan usually takes effect in 10 to 15 minutes (8) (Fig. 95-1). Increasing the dose from 6 to 12 mg neither increases the number of responders, nor enhances the drug’s effect (7). Experience of long-term treatment with sumatriptan is fairly limited in cluster headache, and no evidence of tachyphylaxis has been reported (12) (Fig. 95-2).