Rare cases of severe but reversible cerebral vasospasm have been reported after the use of ergotamine or a serotonin agonist drug, but most of these patients in fact had not had neurologic features as part of their initial headache syndrome. Of particular danger, however, is the often unnoticed, concurrent use of other sympathomimetic drugs such as phenylpropanolamine as in one of the cases described by Singhal and colleagues and by Meschia and associates (see discussion of Call-Fleming syndrome, “Diffuse Vasoconstriction,” “Diffuse and Focal Cerebral Vasospasm” in Chap. 33). Cerebral hemorrhage is another rare complication of serotonin agonist use that possibly relates to hypertension induced by triptans or ergots. Ergot drugs and triptans are contraindicated in symptomatic and asymptomatic coronary artery disease and poorly controlled hypertension.
For severely ill patients who arrive in the emergency department or physician’s office, having failed to obtain relief from a prolonged headache with the above medications, Raskin (1986) has found metoclopramide 10 mg IV, followed by DHE 0.5 to 1 mg IV every 8 h for 2 days, to be effective. We also use this approach as well as intravenous magnesium infusions, starting with 1 g, in cases of status migrainosus. The administration of intravenous DHE can be combined with a lidocaine infusion, this combination having not been exposed to a rigorous clinical trial. The potential success of metoclopramide alone should not be dismissed, as we and others have occasionally found that the headache abates after this initial injection. A wide array of other drugs including almost all of the conventional nonsteroidal anti-inflammatory medications has been recommended as adjunctive therapy, for example, prochlorperazine, ketorolac, and intranasal lidocaine. Each of these drugs, given alone, is effective in alleviating the headache in about half of patients, emphasizing the need for blinded placebo-controlled trials for any drug that is introduced for the treatment of headache.
Intravenous and oral corticosteroids have been found anecdotally to be useful in refractory cases and as a means of terminating migraine status. In a randomized trial of intravenous dexamethasone 10 mg in an emergency department setting, Friedman et al found no benefit. As an alternative to steroids and more commonly used nonsteroidal agents, Weatherall and colleagues used intravenous aspirin (lysine acetylsalicylate, 1 g, repeated up to five times) with reasonably good effect in inpatient management of migraine and other headache disorders. We have determined that this agent is difficult to obtain from our hospital pharmacies.
If, in an individual attack, all of the foregoing measures fail, it may be reasonable to resort briefly to narcotics, which usually give the patient a restful, pain-free sleep. Halfway measures at this point are usually futile. However, the use of narcotics as the mainstay of acute or prophylactic therapy is to be avoided. As mentioned above, if the pain does not abate in 12 to 24 h, corticosteroids in any of several regimens may be added and continued for several days.
Based on the action of certain peptides in the trigeminovascular complex, novel antagonists of CGRP have been investigated, and while symptomatically equivalent to triptans (Olesen and colleagues and also Ho et al), they have been largely abandoned because of liver toxicity with frequent use. Drugs of this type as well as inducible nitric oxide synthase (iNOS) inhibitors and receptor blockers that work by a different mechanism than do the serotonin agonists may be alternatives in the future.