ABORTIVE DRUG THERAPY IN MIGRAINE

Edward Lichten, M.D.,PC
555 S. Old Woodward Avenue Suite 700
Birmingham, MI 48009 
248.593.9999

Email: drlichten
@yahoo.com

 

 

Lecturer #6: Bruce Silverman, D.O.
Neurologist, Senior Attending, Providence Hospital, Southfield, Michigan
 
Novi Headache Symposium 1994

 

TOPICS INCLUDED IN THIS ARTICLE

INTRODUCTION
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The treatment of vascular headaches is both a challenge and enigma. Primarily, there is extreme importance in proper classification, although patients with similar headache types may not respond to the same headache treatment regimen. For this reason, pathogenic origin and therapeutic maneuvers have varied significantly over the years.

Historically, supernatural forces were felt to play a significant role in the origin of headache. The writings of the ancient Sumerians (4000 BC.) suggested that prayers and incantations would "ascend the headache to heaven." Might this be the first description of biofeedback and behavior modification? Later (around 2500 B.C.), Egyptians utilized binding a clay model of a crocodile to the head of the afflicted; was this perhaps the beginning of the musculoskeletal treatment of headache?

The Renaissance period brought a more scientific approach to the treatment of headache, when blood letting was still in vogue: "The painful temples would be incised and as a heated glass globe was applied over it, the cool blood was drawn from the head into the globe." Not until the 19th century did Osler and Gowers begin an attempt to classify headache into acute and chronic varieties and recommend treatment therein.

By the 20th century the experimental headache model began to take shape, and drug therapies catapulted forward. Initially, ergot preparations were developed. Rothlin purified the alkaloid of ergot, which was widely utilized by Maier and Tzank in the 1920's; a major advance in the treatment of migraine. More recently, the importance of serotonin activity has come to the forefront, and the belief that excessive serotonergic activity is at least biochemically responsible for migraine has further advanced our efforts at headache control.

Finally prophylactic therapeutics including beta blockers, calcium channel blockers, 5-HT antagonists, antidepressants and anti-inflammatory agents have contributed to the management of headache.

Initially, the classification of headache will clearly guide the practitioner to the most reasonable approach to treatment. Abortive therapy should be considered in those patients whose frequency of attacks is less than one or two events per week, and used as an adjutant to maintenance therapy for breakthrough attacks.

Emphasis must be on timing in the face of an acute attack. Early institution of abortive drugs in general is correlated with heightened success in treatment of headache. The associated changes that may occur in gastrointestinal motility and absorption can adversely affect the therapeutic response from medications administered. Slowed gastro-intestinal motility with associated nausea/vomiting and diarrhea will alter absorption pharmaco-dynamics and limit responsiveness to oral medications. Concomitant administration of antiemetic drugs such as metoclopramide (Reglan™) and/or phenothiazines can help overcome this difficulty. The antinausea effects of these medications are felt to be mediated through the dopamine D2-receptor blockade, while the gastrokinetic effects may be due to cholinergic activity at muscarinic sites both central and peripherally.

Analgesics are often used to abort acute migraine. The use of various NSAIDs such as ketoprofen (Orudis™), naproxen (Naprosyn™), etc. have been beneficial and are associated with inhibition of prostaglandin synthesis, platelet aggregation, release of serotonin from platelets and release of bradykinin. Finally, by decreasing capillary permeability and the associated inflammatory reaction, relief is obtained.

Careful use of narcotic analgesics in association with an abortive agent in the treatment of acute migraine may be helpful. The sedative effect from these medications often assists with analgesia. Caution must be maintained against abuse potential. Literature supports the greater efficacy of ergot preparations compared to both narcotic and nonnarcotic analgesics.

MIDRIN
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Isometheptene mucate (Midrin) acts as a vasoconstrictor through its sympathomimetic action. It is very effective as an abortive agent in the treatment of migraine. This drug is contraindicated in patients with extreme hypertension, hepatic and renal failure, and concomitant use of MAO inhibitors.

Chlorpromazine (Thorazine™) used in the abortive treatment of migraine has gained favor not only in attempts to abort the acute attack, but its anxiolytic and antinauseant effects are beneficial as well. Dosing varies from 5-50 mg IV or IM.

Corticosteroids have also found their way into the treatment of acute migraine. Their action is likely related to control of inflammatory perivascular response and sensitizing blood vessels to the vasoconstrictive effects of circulating vasoactive substances. Steroids are seldom of help beyond twenty-four hours.

ERGOTAMINE
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Ergotamine preparations have been the most consistently used agent in the acute treatment of migraine. The pharmacological effects include potent vasoconstriction of the external carotid system (in the peripheral vascular tree as well), with little effect on the intracranial vasculature. Therefore, use of ergotamine during the vasoconstrictive aura phase is acceptable. Ergots affect the vascular bed dependent on the preexisting tone, such that with low resistance it may act as a vasoconstrictor and with high resistance it may act as a vasodilator. The vasoconstrictive effects are mediated thorough alpha adrenergic blockade and a direct effect on arterial serotonergic receptors. Furthermore, ergots may cause the closure of A-V shunt channels, suppress release of neurokinin substances and depress firing of serotonergic brainstem nuclei.

Ergots can be administered in a variety of methods including oral, sublingual, inhalation, injectable, and rectal suppository. Nausea is a frequent side effect of these medications and dosage must be maintained at a subnauseating level. Side effects of ergots include nausea, abdominal cramping, dizziness, muscle cramping, seizures (5-10%). Infrequently (<1%) reports of myocardial infarction, cerebral atrophy/infarction, gangrene and death have been described. One must look closely for symptoms of angina and peripheral vascular disease before administering ergots. Dihydroergotamine has the added benefit of primary venoconstriction as a mechanism of action and has little effect on arteries.

SUMATRIPTAN
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Sumatriptan was synthesized by Glaxo in 1984. Initial trials of this medication began as a randomized and double blinded study. Specific inclusion criteria consisted of males and female sat least eighteen years of age, one year history of migraine (as established by the International Headache Society), one to six migraines per month and the ability to distinguish migraine from other headache types. Exclusion criteria included history of ischemic heart disease, uncontrolled hypertension, peripheral vascular disease, Raynaud's disease, renal or hepatic impairment, epilepsy, cerebral infarction, psychiatric illness, pregnancy or lactation. Overall satisfaction of response was as high as seventy percent with sumatriptan versus twenty-two percent in the placebo controlled group.

Sumatriptan is a selective five hydroxytryptamine (5-HT) one receptor agonist. Therefore, evidence supporting a role of 5-HT in the pathogenesis of migraine has led to the development of this compound. Inadequate synthesis of 5-HT, excessive breakdown of 5-HT, formation of an unstable 5-HT and an abnormality of 5-HT receptor function has been suggested in the development of migraine. With this hypothesis and an understanding of the role of serotonin in the development of migraine, 5-HT 1 receptor agonists have been suggested. These receptors act as a neuronal inhibitor and block the release of nociceptive (pain transmitting) substances from the trigeminovascular afferent terminals within the meninges.

Sumatriptan (Imitrex™) is currently available as a intramuscular injection, therefore overriding the potential gastrokinetic malabsorption that may occur with migraine. This drug is specific to binding of the 5-HT 1 receptor sites as its mechanism of action. It is felt that through stimulation of this inhibitory neuroreceptor that migraine termination occurs. The dose of sumatriptan is six milligrams and may be repeated in one hour as needed. The patient must be cautioned to avoid exceeding two shots per day or fourteen shots per week. Also, concomitant use of other vasoconstrictive drugs should be avoided (DHE-45™, Isometheptene). Individuals with ischemic heart disease, myocardial infarction, vasospastic angina, basilar and complicated migraine should not be treated with sumatriptan. Concomitant use of prophylactic migraine therapy as no ill effects on the response to sumatriptan.

Side effects include: injection site reaction, tingling, dizziness/vertigo, warm/hot sensations, burning sensation, feeling of heaviness, pressure sensation, flushing, and feeling of tightness are typically well-tolerated.

 

 
Revised: January 1, 2011