A single 4or 6-mg dose of sumatriptan or its equivalent, given subcutaneously, is an effective and well- tolerated treatment for migraine attacks (see Subcutaneous Sumatriptan Study cited in the references). When successful, it eliminates or reduces the accompanying symptoms of nausea, vomiting, photophobia, and phonophobia. An advantage of the serotonin agonist drugs, aside from their relative safety, is the ease of self-administration using prepackaged injection kits, thus avoiding frequent and inconvenient visits to the emergency department. Sumatriptan can also be given orally in a 25-, 50-, or 100-mg tablet and as a nasal spray (20 mg per spray), zolmitriptan in a 2.5or 5-mg tablet or 5-mg nasal spray, and rizatriptan in a 5or 10-mg dose tablet, repeated, if needed, in 2 h. For oral preparations, latency for headache relief is longer than with subcutaneous injection or inhalation. If one serotonin agonist is found to be ineffective, another drug or an alternative route of administration, such as intranasal, may be tried. These medications are summarized in Table 9-2.
A large and often cited meta-analysis of the available drugs in 53 separate trials conducted by Ferrari and colleagues (2001) found modest differences in overall efficacy between drugs. Loder has given a tabulated comparison of the main drugs for migraine and a review of their use in routine situations.
Ergotamine is an equally effective agent, but its peripheral and coronary vasoconstricting side effects, including nausea, have reduced its use. This is an alpha-adrenergic agonist with strong serotonin receptor affinity and vasoconstrictive action. The drug is taken as an uncoated 1to 2-mg tablet of ergotamine tartrate, held under the tongue until dissolved (or swallowed), or in combination with caffeine. Repeat use is not advisable as it may lead to prolonged or daily headache. A single oral dose of promethazine 50 mg, or of metoclopramide 20 mg, given with the ergotamine, allays the potential nausea and vomiting from ergotamine and may have independent effects on reducing the severity of headache. Patients in whom vomiting prevents oral administration may be given ergotamine by rectal suppository or DHE by nasal spray or inhaler (one puff at onset and another at 30 min) or can learn to give themselves a subcutaneous injection of DHE (usual dosage, 1 mg). Caffeine, 100 mg, is thought, on slim evidence, to potentiate the effects of ergotamine and other medications for migraine. When ergotamine is administered early in the attack, the headache will be abolished or reduced in severity and duration in 70 to 75 percent of patients.
An important problem pertains to the risk of stroke from serotonin agonists in patients with prolonged visual aura or other focal neurologic symptoms associated with the headache. What evidence exists suggests the risk of stroke is low or nonexistent as, for example, in the epidemiologic study by Hall and colleagues. As a matter of course, however, serotonin agonists and ergots are generally avoided if there is an ongoing and prolonged aura of any type, including visual, but particularly with hemiparesis, aphasia, or features such as vertigo, drowsiness, or diplopia, referable to the basilar artery. Not all experts agree with this proscription and some small series, among them 13 patients reported by Klapper and colleagues, have found triptans safe to use if a headache with neurologic signs has commenced, but this issue has not been resolved. As previously noted, although this class of drugs may not be helpful during the visual aura, they also seem to do no harm (see Bates et al).