Cafergot

Migraine headaches are a major public health problem affecting more than 28 million persons in this country. (1) Nearly 25 percent of women and 9 percent of men experience disabling migraines. (2,3) The impact of these headaches on patients and their families is tremendous, with many patients reporting frequent and significant disability. (4) The economic burden of migraine headaches in the United States is also tremendous. Persons with migraines lose an average of four to six work days each year, with an annual total loss nationwide of 64 to 150 million work days. The estimated direct and indirect costs of migraine approach $17 billion. (5,6) Despite the prevalence of migraines and the availability of multiple treatment options, this condition is often undiagnosed and untreated. (7) About one half of patients stop seeking medical care for their migraines, in part because of dissatisfaction with the therapy they have received. (4)

Patients with migraine headaches often present family physicians with diagnostic and therapeutic challenges. The aspects of migraine management that deserve careful consideration include the treatment of acute pain, the role of neuroimaging, and the management of patients who fail to respond to initial treatment. This article addresses these issues, presenting the evidence-based migraine headache treatment guidelines recently established by the U.S. Headache Consortium, a multidisciplinary team consisting of members from seven organizations, including the American Academy of Family Physicians (AAFP). The guidelines are available on the AAFP Web site. (8)

Clinical Presentation

The classification of migraines is based on the clinical features of the headache, most notably the presence or absence of a characteristic aura before the onset of pain. The aura may take many forms but usually involves visual distortions, including scotomas. Other prodromal symptoms described by many patients with migraines include nausea, food cravings, heightened sensory perceptions, and alterations in mood or behavior.

The International Headache Society's categorization of headaches is listed in Table 1. (9) Migraines can be triggered by hormonal changes, certain foods, sensory stimuli (i.e., light, smells), missed meals, or the relief of tension after stressful events.

Evaluation

The initial task in managing a patient who presents with migraine headache is to take a detailed history and perform a thorough physical and neurologic examination. Patients may present with significant expectations derived from the numerous sources of information available, especially those on the Internet. One of the most popular and authoritative Web sites is that of the National Headache Foundation (NHF) (http://www.headaches.org/). The NHF site provides patients with a "checklist" of questions that primary care physicians should ask when taking an appropriate history (Table 2). (10)

This site can be a highly useful part of patient education, but family physicians should be aware that it advises patients to seek referral to a subspecialist or headache clinic if the primary care physician does not appear to appropriately appreciate, diagnose, or treat the headache. This suggestion may raise concern in some patients about the ability of primary care physicians to appropriately manage headaches. Family physicians might ask patients about their sources of medical information.

Physicians may struggle to determine the appropriate use of neuroimaging in the patient with migraine. The American Academy of Neurology suggests that neuroimaging should be considered only in patients with migraine who have atypical headache patterns or neurologic signs (11); the U.S. Headache Consortium has developed evidence-based guidelines on the use of neuroimaging for patients with migraines.

In general, the U.S. Headache Consortium guidelines do not recommend neuroimaging if the patient is not at higher risk of a significant abnormality than the general population or if the results of the study would not change the management of the headache. Symptoms that increase the odds of positive neuroimaging results include rapidly increasing frequency of headache, a history of uncoordination, focal neurologic signs or symptoms, and a headache that awakens the patient from sleep. Other "red flags" include abrupt onset of severe headache, marked change in headache pattern, or persistent headache following head trauma. The specific U.S. Headache Consortium guidelines for neuroimaging are outlined in Table 3. (12)

Electroencephalography is not useful in the routine evaluation of patients with headache but may be appropriate in those who have associated symptoms suggestive of a seizure disorder, atypical migrainous aura, or episodic loss of consciousness. (13)

Goals of Migraine Treatment

Migraine treatment depends on the duration and severity of pain, associated symptoms, degree of disability, and initial response to therapy. Management of migraines can be difficult because of the complexity of migraines and the variation of symptoms among and within patients. Some medical conditions (stroke, myocardial infarction, epilepsy, affective and anxiety disorders, and some connective tissue disorders) are more common in people with migraine. These conditions provide opportunities to treat both conditions with one medication but are also limiting because of drug interactions or contraindications. Appropriate migraine therapy should allow for consideration of the above factors. (14)

The U.S. Headache Consortium identified the goals of long-term migraine treatment and successful management of acute migraine (Tables 4 and 5). (14) These goals emphasize the importance of patient education and self-participation in the management of migraines, and of establishing reasonable patient expectations and effective communication. Of note, these treatment goals are also designed to avoid "rebound" or medication-overuse headaches. Frequent use of some migraine medications (e.g., ergotamine [Ergostat], opiates, analgesics, and triptans) may cause medication-overuse headaches. Preventive therapy should be considered if the patient has more than two headaches per week. (15)

If identified early, a migraine may be aborted with pharmacologic treatment using either nonspecific or migraine-specific medications. Gastrointestinal motility is reduced during acute migraine, causing impaired drug absorption. If administration of oral medication is not possible because of nausea or if the oral agents fail, alternative methods of administration (rectal, nasal, subcutaneous or intravenous) may be used for many medications.

Nonspecific Abortive Migraine Therapy

Table 6 (4,16-18,22) lists the nonspecific treatments that may be effective for mild to moderate migraines. Non-narcotic analgesics can be used for mild to moderate migraines that are not associated with nausea and vomiting. Administration as early as possible during an attack improves efficacy. The use of these analgesics should be closely monitored because overuse may lead to rebound headaches.

Acetaminophen alone has not been shown to be beneficial in migraine treatment, but it is effective in combination with aspirin and caffeine. Ketorolac (Toradol), a parenteral nonsteroidal anti-inflammatory drug (NSAID), has a relatively rapid onset of action and a duration of approximately six hours. It is generally reserved for abortive therapy of severe migraines, and rebound headache is unlikely. Opioid analgesics such as meperidine (Demerol) and butorphanol (Stadol) are sometimes required to abort severe migraines. Narcotic use should be avoided for chronic daily headaches because it can lead to dependency, rebound headaches, and eventual loss of efficacy.

Adjunctive therapy is used to treat the associated symptoms of migraine and provide synergistic analgesia. While metoclopramide (Reglan) is sometimes recommended as a single agent in the treatment of migraine pain, its main use is for treating accompanying nausea and improving gastric motility, which may be impaired during migraine attacks. Prochlorperazine (Compazine) can effectively relieve headache pain. (19,20) Other adjunctive therapies for the abortive treatment of migraines are caffeine and sleep.

The combination of isometheptene, acetaminophen, and dichloralphenazone (Midrin) has been shown to be effective in the treatment of milder migraine headaches. (10,21) Sedatives such as the barbiturates have historically been used to induce sleep in persons with migraines. However, with the advent of effective nonsedating agents and migraine-specific therapy, sedatives are no longer widely used in migraine therapy.

Other nonspecific therapies that have been used to abort acute migraine attacks include intranasal lidocaine (Xylocaine) and systemic steroids. While limited studies report lidocaine to be superior to placebo, the reported incidence of recurrent headaches has been inconsistent. Because the evidence is insufficient, a defined role for intranasal lidocaine as abortive migraine therapy has yet to be established. Steroid therapy may be the treatment of choice for patients with status migrainosus (a severe, continuous migraine that may last up to one week), but there are no good studies documenting its efficacy in the treatment of the acute migraine attack. (14)

Specific Abortive Migraine Therapy

ERGOTAMINE AND ITS DERIVATIVES

Historically, ergotamine, a 5-hydroxytryptamine (5-H[T.sub.1]) nonselective agonist, was the standard abortive migraine therapy. It now has a more limited use because of its potential for causing medication-overuse headaches and increasing the frequency of headaches, ergot poisoning, and negative effects on migraine prophylactic medications. The effectiveness of ergotamine depends on its administration at the onset of migraine pain. (22)

Oral preparations combining ergotamine and caffeine (Cafergot) are available, as are rectal suppositories. Dihydroergotamine (DHE), a semisynthetic ergot alkaloid and nonselective 5-H[T.sub.1] receptor agonist, is considered to be more appropriate for the treatment of severe migraines. It is available in parenteral preparations and as a nasal spray. Like ergotamine, DHE has oxytocic properties, precluding its use in pregnancy. Because of their ability to cause peripheral vasoconstriction, ergot alkaloids should not be used chronically. The ergotamine derivatives used to treat migraines are described in Table 7. (4,16-18,22)

TRIPTANS

A widely prescribed and effective class of medications for migraines is the 5-H[T.sub.1] receptor-specific agonists ("triptans"). The use of triptans in the treatment of migraine headaches is described in Table 7. (4,10,16-18) Triptans are usually reserved for use in patients with moderate to severe migraines or mild to moderate migraines that are unresponsive to analgesics or NSAIDs. As a class, triptans are usually well tolerated. Contraindications to their use include ischemic vascular conditions, vasospastic coronary disease, uncontrolled hypertension, or other significant cardiovascular disease. While members of the triptan family are similar in many ways, there are significant differences in time to peak blood concentration and half-life.

Subcutaneously injectable sumatriptan (Imitrex) reaches peak blood concentrations faster than any other migraine-specific medications (in approximately 15 minutes) and has been shown to be effective in 70 to 82 percent of patients. The oral form of rizatriptan (Maxalt) reaches peak concentration in 60 to 90 minutes, compared with two to three hours for most other triptans. The longest half-life of the triptans belongs to naratriptan (Amerge). There is some speculation that this longer half-life will decrease the chance of recurrence headaches. In general, if recurrence occurs with use of the triptans, it occurs within eight to 12 hours and can be relieved with a second dose of the medication. (16,23)

Some triptans have the benefit of non-oral routes of administration. Sumatriptan is available in subcutaneous or intranasal form, while rizatriptan (as Maxalt MLT) is offered in an absorbable wafer. When significant nausea and/or vomiting are part of the migraine syndrome, these choices may be better for the patient. Frovatriptan (Frova) and almotriptan (Axert) are oral triptans approved by the U.S. Food and Drug Administration. These and eletriptan (under development) are reportedly more effective, have fewer adverse reactions, and have a more rapid onset of action than sumatriptan.

Several important principles of migraine management have emerged from clinical trials of migraine-specific treatments. First, patients should try a medication for two to three headache episodes before abandoning that line of therapy. Second, if one triptan is ineffective in a patient, a different triptan should be tried. In addition, in selecting a migraine-specific drug, the characteristics of the drug should be matched with the patient's needs and the usual duration of the headache. (17,18)

Various approaches exist for the management of migraine headaches. In the "step-care" approach, patients with acute migraine attacks are initially treated with the safest, least expensive therapies and progress to the more expensive migraine-specific medications, such as the triptans, only when the initial treatment fails. (24) In contrast, the "stratified-care" approach assigns treatment based on the severity of migraine-related disability, with the nonspecific therapies used in patients with little or infrequent disability, and the migraine-specific medications used in patients with moderate to severe disability. In a recent randomized trial, the stratified-care approach was found to be superior to the step-care approach. (25)

Nonpharmacologic Alternatives to Migraine Therapy

Because of the current popularity of complementary and alternative therapies, many patients may first request nonpharmacologic treatment. In their consensus guidelines, the U.S. Headache Consortium reviewed behavioral and physical treatments for migraine headaches. Based on available evidence, it appears that relaxation training, thermal biofeedback combined with relaxation training, electromyographic biofeedback, and cognitive-behavioral therapy may be effective in preventing migraines. Behavioral therapy such as relaxation or biofeedback may be combined with preventive drug therapy to achieve additional clinical improvement. Other modalities, such as acupuncture, hypnosis, transcutaneous electrical nerve stimulation, cervical manipulation, occlusal adjustment, and hyperbaric oxygen, have shown mixed results in reported studies but may be worth trying in patients who want to use medication only as a last resort.

The authors indicate that they do not have any conflicts of interest. Sources of funding: none reported.

REFERENCES

(1.) National Headache Foundation. NHF headache facts. Retrieved April 2002, from: www.headaches.org/factsheet.html.

(2.) Rasmussen BK, Jensen R, Schroll M, Olesen J. Epidemiology of headache in a general population--a prevalence study. J Clin Epidemiol 1991;44:1147-57.

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(6.) Cady RK. Diagnosis and treatment of migraine. Clin Cornerstone 1999;1:21-32.

(7.) Bartleson JD. Treatment of migraine headaches. Mayo Clin Proc 1999;74:702-8.

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(9.) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Headache Classification Committee of the International Headache Society. Cephalalgia 1988;8 Suppl 7:1-96.

(10.) Moore KL, Noble SL. Drug treatment of migraine: part I. Acute therapy and drug-rebound headache. Am Fam Physician 1997;56: 2039-48.

(11.) Frishberg BM. The utility of neuroimaging in the evaluation of headache in patients with normal neurologic examinations. Neurology 1994;44:1191-7.

(12.) Frishberg BM, Rosenberg JH, Matchar DB, McCrory DC, Pietrzak MP, Rozen TD, et al. U.S. Headache Consortium. Evidence-based guidelines in the primary care setting: neuroimaging in patients with nonacute headache. Retrieved April 2002, from: www.aan.com/public/practiceguidelines/02.pdf.

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(14.) Matchar DB, Young WB, Rosenberg JH, Pietrzak MP, Silberstein SD, Lipton RB, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. U.S. Headache Consortium. Retrieved April 2002, from: www.aan.com/public/practiceguidelines/03.pdf.

(15.) Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:754-62.

(16.) Dooley M, Faulds D. Rizatriptan: a review of its efficacy in the management of migraine. Drugs 1999;58:699-723.

(17.) Stark S, Spierings EL, McNeal S, Putnam GP, Bolden-Watson CP, O'Quinn S. Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan. Headache 2000;40:513-20.

(18.) Mathew NT, Kailasam J, Gentry P, Chernyshev O. Treatment of nonresponders to oral sumatriptan with zolmitriptan and rizatriptan: a comparative open trial. Headache 2000;40:464-5.

(19.) Jones J, Pack S, Chun E. Intramuscular prochlorperazine versus metoclopramide as single-agent therapy for the treatment of acute migraine headache. Am J Emerg Med 1996;14:262-4.

(20.) Coppola M, Yealy DM, Leibold RA. Randomized, placebo-controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. Ann Emerg Med 1995;26:541-6.

(21.) Jackson CM. Effective headache management. Postgrad Med 1998;104:133-47.

(22.) Tfelt-Hansen P, Saxena PR, Dahlof C, Pascual J, Lainez M, Henry P, et al. Ergotamine in the acute treatment of migraine: a review and European consensus. Brain 2000;123(pt 1):9-18.

(23.) Diener HC, Kaube H, Limmroth V. Antimigraine drugs. J Neurol 1999;246:515-9.

(24.) Matchar DB, McCrory DC, Gray RN. Toward evidence-based management of migraine. JAMA 2000;284:2640-1.

(25.) Lipton RB, Stewart WF, Stone AM, Lainez MJ, Sawyer JP. Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) Study: a randomized trial. JAMA 2000;284:2599-605.

Members of various medical faculties develop articles for "Practical Therapeutics." This article is one in a series coordinated by the Department of Family Medicine at Ohio State University College of Medicine and Public Health, Columbus. Guest editor of the series is Doug Knutson, M.D.

GLEN AUKERMAN, M.D., is professor in the Department of Family Medicine at Ohio State University College of Medicine and Public Health in Columbus. He received his medical degree from Ohio State University College of Medicine. Dr. Aukerman is past president of the Ohio Academy of Family Physicians and the American Academy of Family Physicians.

DOUG KNUTSON, M.D., is assistant professor in the Department of Family Medicine at Ohio State University. He received his medical degree from Ohio State University College of Medicine and completed a residency in family medicine at Riverside Methodist Hospital in Columbus, Ohio.

WILLIAM F. MISER, M.D., M.A., is associate professor in the Department of Family Medicine at Ohio State University, where he also serves as residency director. Dr. Miser received his medical degree from Ohio State University College of Medicine and completed a residency in family medicine in Augusta, Ga.

Address correspondence to Glen Aukerman, M.D., Department of Family Medicine, Ohio State University College of Medicine and Public Health, 2231 N. High St., Columbus, OH 43201 (e-mail: aukerman-1@medctr.osu.edu). Reprints are not available from the authors.

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