Zolmitriptan

Bahra A, Gawel MJ, Hardebo J-E, Millson D, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurol 2000; 54:1832-39.

* BACKGROUND Acute treatments for cluster headaches include oxygen, ergotamine derivatives, and intranasal or subcutaneous sumatriptan. Although up to 95% of acute cluster headache patients treated with subcutaneous sumatriptan experience pain relief within 15 minutes,[1] the route of administration and restrictions on recommended daily dosage may limit patient use of this therapy. Oxygen is effective as abortive therapy but is frequently unavailable in settings where acute cluster headaches are experienced. Rectal and oral ergotamine derivatives have poor bioavailability, and all ergot alkaloids have a high incidence of adverse effects. Oral zolmitriptan is efficacious in the acute treatment of migraine headache. However, no previous studies have evaluated the efficacy of oral triptans in the treatment of cluster headaches.

* POPULATION STUDIED The authors of this study included patients aged 18 to 65 years who were recruited from multiple specialty referral centers in Canada, the United Kingdom, and Sweden. All subjects had an established diagnosis of chronic or episodic cluster headache, described as headaches typically lasting 45 minutes or longer that were distinguishable from other types of episodic headaches, and had tolerated previous treatment with a 5-hydroxytryptamine (5-HT) agonist, such as sumatriptan or ergotamine. The study excluded patients with a history of basilar, ophthalmoplegic, or hemiplegic migraine, and those with risk factors contraindicating the use of 5-HT agonists.

* STUDY DESIGN AND VALIDITY This randomized double-blinded placebo-controlled crossover study compared 5-mg and 10-mg doses of zolmitriptan with placebo for the acute treatment of cluster headaches. Headache intensity was rated on a diary card with a 5-point severity scale (no, mild, moderate, severe, or very severe pain); only headaches of moderate to very severe intensity were treated. Subjects were required to take the study medication within 10 minutes of headache onset, were not permitted to take escape medications, such as oxygen or analgesics, within 30 minutes of taking study medications, and were not permitted to institute prophylactic treatment during the study period. Subjects whose cluster headache period ended before treatment or who had fewer than 3 headaches before the end of the study period were excluded from the analysis. Those who failed to comply with the strict requirements for medication use were noted, but were still included in the intention-to-treat analysis. This is a well-designed study, with no major threats to validity. Patients were selected from referral centers and thus may differ from cluster headache sufferers in a primary care clinic population.

* OUTCOMES MEASURED The primary outcome was headache improvement at 30 minutes, defined as a reduction in headache intensity of 2 or more points on the 5-point scale. Secondary treatment outcomes included the proportion of subjects experiencing any headache relief at 15 and 30 minutes, experiencing headache relief at any time, using escape medication 30 to 180 minutes after treatment, having mild or no pain 30 minutes after treatment, and obtaining relief of associated symptoms. Subjects in each study arm were also asked to indicate their preferred treatment.

* RESULTS Different treatment responses were found for episodic and chronic cluster headache subgroups (the latter patients had attacks for more than a year without remission). Chronic cluster headache subjects showed no statistically significant treatment response to zolmitriptan. Compared with placebo, a greater proportion of episodic cluster headache sufferers experienced a 2-point reduction in headache intensity after taking 10 mg of zolmitriptan (47% vs 29%). Six patients would need to be treated with this dose for 1 patient to improve this much (number needed to treat [NNT]=6). Use of 10 mg zolmitriptan was also associated with statistically significant improvement in all of the secondary outcomes. Patients treated with 5 mg zolmitriptan had improvement in only 3 secondary outcomes: headache relief at any time (NNT=6), lower likelihood of escape medication use (NNT=5), and mild or no pain at 30 minutes (NNT=7). Zolmitriptan was associated with a significantly greater incidence of medication-related adverse effects (number needed to harm=5 for the 10-mg dose). The most frequently described adverse effects were paresthesia, heaviness, asthenia, nausea, dizziness, and (nonchest) tightness. No medication-related events led to withdrawal from the study. Forty-five percent of subjects preferred the 10-mg dose compared with 29% who preferred the 5-mg dose, and 26% the placebo.

RECOMMENDATIONS FOR CLINICAL PRACTICE

Oral zolmitriptan (particularly the 10-mg dose) is efficacious in acute treatment of episodic cluster headaches. Because of its ease of administration relative to other treatment options, oral zolmitriptan may be a good choice for patients unable to use sumatriptan. However, it shares similar adverse effects with other 5-HT agonists and has a slower onset of action compared with subcutaneous sumatriptan. Head-to-head trials in primary care populations comparing oral zolmitriptan with abortive oxygen treatment and with different forms of sumatriptan are needed to better establish the role of zolmitriptan in management of cluster headaches.

REFERENCE

[1.] Hardebo JE, Dahlof C. Sumatriptan nasal spray (20 gm/dose) in the acute treatment of cluster headache. Cephalgia 1998; 18:487-89.

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