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Symptomatic
Treatment There are a wide variety of acute treatments available for migraine. (Table 7): Table 7. Drugs Used for Acute Migraine Therapy
A further listing of abortive and symptomatic therapies for migraine is adapted from Baumel.{207} (Tables 8 & 9): Table 8. Abortive therapy for migraine
Table 9. Symptomatic therapy for migraine
As pointed out by Silberstein and Lipton, the choice of acute treatment depends upon the severity and frequency of headaches, the pattern of associated symptoms, comorbid illnesses, and the patient's treatment response profile. The simplest treatment is with non-prescription or prescription analgesics. Many individuals find headache relief with compounds such as aspirin or acetaminophen either alone or in combination with caffeine. Butalbitol, a short-acting barbiturate is often added to the combination of simple analgesics and caffeine. The combination of acetaminophen, isometheptene, a sympathomimetic; and dichloralphenazone, a chloral hydrate derivative, is also safe and effective in headache treatment.{217,218} When simple analgesics fail, consideration may be given to combination with more potentially habit forming medication. Combinations are available with codeine. The nausea is often effectively treated with prochloperazine. More potent narcotic analgesics such as propoxyphene, meperidine, morphine, hydromophone, and oxycodone are available alone and in combination. However, because of medication overuse and rebound, these agents should be used sparingly and only for patients who experience infrequent headaches.{14} Silberstein and Lipton {9} further discuss the use of opioids including those transnasally delivered. Ergotamine and DHE can be used to treat moderate to severe migraine.{219} It was once the mainstay of acute therapy. It was once said that "if a headache does not respond to ergotamine tartrate, it is not true migraine."{220} This agent, derived from Claviceps purpurea, a fungus that grows in rye and other grains, is the major compound effective as a specific agent in an acute migraine attack. The interested reader may also enjoy the novel: Acceptable Risk by Robin Cook which discusses other aspects of the alkaloids derived from rye. Ergotamine is one of the naturally occurring alkaloids in crude ergot; all the ergot alkaloids are derivatives of lysergic acid.{221} Ergotamine has as one of its major pharmacologic properties the ability to produce a peripheral vasoconstriction and, in higher doses, damages capillary endothelium. Inasmuch as ergotamine is neither sedative nor analgesic and other forms of pain are not relieved by the drug, its action is believed to directly related to the pathophysiology of migraine. In the classic experiments of Graham and Wolff,{222} the intensity of pain was directly related to the amplitude of the temporal artery pulsation, and both decline in response to intravenous ergotamine tartrate. (Fig. 13):  Figure 13. Relation of amplitude of pulsations of temporal artery to intensity of headache after administration of ergotamine tartrate. The sharp decrease in the amplitude of pulsation following injection of ergotamine closely paralleled the rapid decrease in intensity of headache. Representative sections of photographic record are inserted. The average amplitude of pulsations for any given minute before and after administration of ergotamine was ascertained by measuring individual pulsations from the photographic record. The points on the heavy black line (lower half) represent these averages, expressed as percentages. Initial or "control" amplitude was taken as 100%. (Dalessio DJ: Wolff's Headache and Other Head Pain, 3rd ed. New York, Oxford) DHE is available in 1mg/mL ampules, which can be administered IM, subcutaneuously (SC), or with IV. 14 A nasal spray with 40% bioavailability is also available. It requires the user to open a vial and place it in an inhaler. A new delivery system in which a vial does not have to be borken open is awaiting FDA approval. Dosage for individual attacks should be limited to 1mg IM or IV, with a maximum of 3mg/d. Monthly limits, according to Silberstein and Lipton, are 18 ampules or 12 events. The oral combination for Egotamine tartrate with caffeine (Cafergot: 1 mg ergotamine tartrate and 100 mg of caffeine) remains widely used. The oral absorption of ergotamine is erratic. While often effective, it shares the disadvantage of most of the oral ergotamine preparations in that it can produce nausea and vomiting itself. However, patients who cannot tolerate ergotamine because of nausea can be pretreated with metoclopramide, {223}proclorperazine, promethazine{224} or a mixture of a barbiturate and a belladonna alkaloid. Intravenous DHE is recommended for patients with intractable migraine.{225} It should be noted that pregnant women should not use ergot preparations because of their potent oxytocic effects. Fortunately, pregnancy usually brings a diminution in the symptoms of migraine. Ergot preparations in high doses may cause peripheral capillary endothelial damage, peripheral paresthesias, pain, and even gangrene. These preparations are generally not recommended for patients in septic states or who have coronary artery disease, obliterative peripheral vascular disease, or cardiac conditions. Is it advisable to use vasoconstricting agents during a complicated migraine prodrome, such as mild hemiparesis or dysphasia? If the cerebral event is indeed vasoconstriction, will ergot preparations potentiate the possibility of permanent cerebral infarction? Theoretically, the preparations act only peripherally and not on the intracranial vasculature. However, since little is really known of the actual central nervous system effects of the ergot alkaloids,{221} it may be wise to be cautious with their use if prominent central nervous system symptoms precede the headache attack. Triptans Sumatriptan (IMITREX®, Galaxo-Wellcome) was introduced in 1993 for the acute treatment of migraine. Since then other triptans have been introduced including: naratriptan (AMERGE®, Galaxo-Wellcome); zolmitriptan (ZOMIG®, Zeneca); and rizatriptan (MAXALT ®, Merck). These agents are selective 5-HT1 receptor agonists. Cady et al{226} found that sumatriptan (6mg SC) was more effective than placebo in reducing moderate or severe pain to mild or no pain (70% vs 22%) and in completely relieving pain (49% vs 9%) after 1 hour. These agents are now the most widely used acute abortive agents.{207} The efficacy of oral sumatriptan in a 100mg dosage is comparable with that of the subcutaneous injection but the onset of treatment effects longer.{208,227} The initial starting dose is of oral sumatriptan is 25mg taken with fluids. The maximum recommended single dose is 100mg. If a satisfactory response is not obtained in two hours, a second dose of up to 100mg may be given. If headache returns, additional doses may be taken at intervals of at least two hours up to a maximum daily dosage of 300mg.{208-211} Specific contraindications to the use of sumatriptan include ischemic heart disease, Prinzmetal's angina, and vertebrobasilar migraine. Side effects include pain at the injection site, tingling, flushing, burning, and warm or hot sensations. Dizziness, heaviness, neck pain, and dysphoria can occur. These side effects generally abate within 45 minutes. There is a separate review of the Triptans on the next page. |
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