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Treatment of Migraine Headaches

  • J.D. Bartleson
    Correspondence
    Address reprint requests and correspondence to J. D. Bartleson, MD, Department of Neurology, Mayo Clinic Rochester, 200 First St SW, Rochester, MN 55905
    Affiliations
    Department of Neurology, Mayo Clinic Rochester, Rochester, Minn
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      Migraine headaches are common and costly. Patients with migraine frequently seek medical attention from primary care physicians. Although effective therapy is available, migraine is underdiagnosed and undertreated. The 3 main forms of management are avoidance of migraine triggers, treatment of the acute attack with medications, and regular use of preventive medications. Although changes in lifestyle can help to prevent some migraine attacks, the mainstay of treatment is the use of medications taken early during the attack. A wide variety of single-ingredient and combination over-the-counter and prescription medications are now available. Especially effective are the new selective serotonin (5-hydroxytryptamine
      • Olesen J
      • Tfelt-Hanscn P
      • Welch KMA
      • et al.
      receptor) agonists such as somatriptan. For patients who have frequent and severe migraine headaches despite the use of acute treatment, preventive medications, including β-adrenergic blockers, calcium channel blockers, tricyclic antidepressants, and one anticonvulsant, should be considered. The vast majority of patients with migraine can be helped.
      DHE (dihydroergotamine), S-OT (S-hydroxytryptamine)
      The National Headache Foundation estimates that US businesses lose $50 billion each year because of absenteeism, reduced employee productivity, and medical expenses caused by headaches. Migraine, the most common cause of severe recurring headache, accounts for most of this financial loss. In a given year, 15% to 20% of women and about 7% to 10% of men will have at least 1 migraine attack.
      • Olesen J
      • Tfelt-Hanscn P
      • Welch KMA
      • et al.
      Prevalence is highest in the 25- to 55-year age-group. Many patients self-treat their migraine attacks, and most who seek professional help will be seen in a primary care setting. Migraine-type headaches are not recognized in many patients. Patients in whom migraine is diagnosed often receive suboptimal treatment. Fortunately, effective therapy is now available for migraine. This review focuses on treatments that can be prescribed by primary care providers for adults and most adolescents with migraine headaches.

      Diagnosis Of Migraine

      Diagnostic criteria for migraine with and without aura have been developed by the International Headache Society
      • Headache Classification Committee of the International Headache Society
      Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain.
      (Tables 1 and 2). Migraine without aura is more common, especially in women. Patients can experience migraine with aura, migraine without aura, or both types. Migraine aura can occur without accompanying headache. The migraine aura characteristically lasts 10 to 30 minutes and usually affects vision but can affect somatic sensation, speech, and motor function. About two thirds of patients with migraine have a family history of the condition.
      Table 1International Headache Society Criteria for Migraine Without Aura
      • Olesen J
      • Tfelt-Hanscn P
      • Welch KMA
      • et al.
      A.At least 5 attacks fulfilling criteria in B, C, D, and E
      BHeadache lasts 4 lo 72 h if untreated or unsuccessfully treated
      C.Headache has at least 2 of the following characteristics:
      • 1.
        Unilateral location
      • 2.
        Pulsating quality
      • 3.
        Moderate to severe intensity
      • 4.
        Aggravation by walking stairs or similar physical activity
      DDuring headache, at least 1 of the following:
      • 1.
        Nausea, vomiting, or both
      • 2.
        Photophobia and phonophobia
      E.History, physical and neurologic examinations, and, if appropriate, diagnostic tests exclude related organic disease
      Table 2International Headache Society Criteria for Migraine With Aura
      • Headache Classification Committee of the International Headache Society
      Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain.
      A.At least 2 attacks that fulfill criteria in B and C
      B.At least 3 of the 4 following characteristics:
      • 1.
        One or more fully reversible aura symptoms indicating focal cerebral cortical or brain-stem dysfunction (or both)
      • 2.
        At least 1 aura symptom develops gradually over >4 min or 2 or more symptoms occur in succession
      • 3.
        No single aura symptom lasts >60 min
      • 4.
        Headache begins during aura or follows aura with a symptom-free interval of 60 min (headache may begin before or with aura)
      C.History, physical and neurologic examinations, and, if appropriate, diagnostic tests exclude related organic disease
      The diagnostic criteria for migraine are probably too strict; for a headache to be a migraine, it does not need to be unilateral, pulsate, or last more than 4 hours. Tension-type headaches (tension or muscle contraction headaches) have probably been overdiagnosed in the Any episodic headache should be considered possible migraine; the likelihood increases if the pain is asymmetric, throbbing, or accompanied by light sensitivity, noise sensitivity, or gastrointestinal symptoms such as nausea. The following signs and symptoms are cause for concern, even if the patient has a history of clear-cut migraine headaches: progressively worsening headaches, a new or different type of headache, the “worst-ever” headache, headaches that reach maximal severity at onset, new headaches after the age of 40 years, headache precipitated by the Valsalva salva maneuver, evidence of systemic disease, persistent neurologic signs and symptoms, and a history of seizure disorder.
      • Institute for Clinical Systems Integration
      Health Care Guideline: Migraine Headache.

      Physician Approach

      The clinician's approach to the patient with migraine is critical for effective treatment. Physicians should be empathetic, be interested in their patients' symptoms, and demonstrate knowledge. They need to determine their patients' objective in seeking help: do they want help with pain or nausea or reassurance that they do not have a major underlying medical or neurologic problem? Reassurance and education can be beneficial. The generally benign outcome of individual migraine attacks and the excellent long-term prognosis for patients with migraine should be emphasized. In some instances, brain imaging can provide additional reassurance for both the patient and the provider.
      The 3 ways to manage migraine are avoidance of factors that can trigger an attack, treatment of the acute headache, and use of regular medication to prevent attacks. The first 2 approaches are usually combined and, if appropriate, preventive medication is added.

      Migraine Triggers

      Many factors have been associated with the provocation of individual migraine attacks: fasting, alcohol, oral contraceptives and hormone replacement therapy, caffeine and caffeine withdrawal, stress or release from stress, too little or too much sleep, menstruation, fatigue, change in weather, head trauma, exposure to bright lights, loud noises, smoke, and strong scents, and foods, including chocolate, aged cheeses, cured and processed meats that contain nitrites, dairy products, those with monosodium glutamate or aspartame, citrus fruits, and others. Patients should be informed about these potential migraine triggers and be instructed to look for them. Identifying migraine triggers and monitoring the patient's response to treatment can be facilitated with a headache diary in which the patient logs precipitating factors, headache characteristics, and details of therapy, including beneficial and adverse effects.
      In general, searching for and trying to avoid migraine triggers are not highly effective for most patients. First, most migraine headaches are not caused by an identifiable trigger. Second, a patient's response to a trigger varies—sometimes fasting will trigger a migraine and sometimes it will not—a factor that decreases the patient's will to avoid all recognized triggers. Third, many of the triggers are unavoidable.

      Treatment

      Acute Migraine Attack

      For most patients, early treatment of the migraine attack is the mainstay of therapy. Prompt treatment is intended to decrease the severity of pain, prevent or reduce associated symptoms such as nausea and vomiting, and shorten the attack duration. Three points deserve emphasis. First, early treatment is critical to obtaining benefit. For most patients, if they wait too long, they lose a “window of opportunity” to stop their migraine attack. Taking medication early during the course of migraine runs counter to human nature—we prefer not to take medications at all and try to wait as long as possible with the hope that symptoms will subside spontaneously. Therefore, patients must be encouraged to treat individual migraine attacks promptly. Second, rest, with or without sleep, usually in a dark and quiet environment, early during the course of a headache can be helpful in decreasing the duration of attack. Of course, this approach is not always feasible. Third, numerous medications are available for early treatment, and the patient may need to try several before finding I or more that are helpful.
      Some of the many available treatment options are listed in Table 3, with the usual dose, common adverse effects, and estimated cost. The list was obtained from various sources1,3–8 and is not all-inclusive.
      Table 3Selected Medications for Migraine
      GI = gastrointestinal; 5-HT1 = serotonin (5-hydroxylryplamine1); 1 M = intramuscularly; IV = intravenously; OTC = over-the-counter; SC = subcutarieously; SL = sublingually.
      Type of drugDose rangeMaximal dose in 24 hAdverse effectsRelative cost per dose
      Treatment of acute attack
       Single-ingredient OTC analgesic
        Acetaminophen500–1000 mg every 4–6 h4000 mgLiver toxic ityPennies
        Aspirin500–1000 mg every 4 6 h4000 mgGI upsetPennies
        lbuprofen200–800 mg every 4–6 h2400 mgGI upsetPennies
        Naproxen sodium220–550 mg every 6–8 hHOOmgGI upsetPennies
       Combination OTC analgesic
        Aspirin and caffeine with or without acetaminophenDosage varies, 1 −2 tablets every 4–6 h
      • Aspirin, 4000 mg
      • Acetaminophen, 4000 mg
      GI upset, liver toxicity, insomniaDimes
       Prescription analgesics
        Acetaminophen, 325 mg, isometheptene, 65 mg. and dichloralphenazone, lOOmg2 capsules at onset, then 1 every hour for 3 h or until headache is gone8 capsulesLiver toxicity, dizzinessDimes
        Butalbital and aspirin or acetaminophen with or without caffeineDosage varies, 1–2 tablets every 4–6 h6 tabletsDrowsiness, dependence, GI upset, liver toxicity, insomniaDimes
        Propoxyphene napsylate, 100 mg, and acetaminophen, 650 mg1 tablet every 4–6 h6 tabletsDrowsiness, dependence, liver toxicityDimes
        Acetaminophen, 300 mg, and codeine, 15–60 mg1–2 tablets every 4–6 h
      • Codeine, 360 mg
      • Acetaminophen, 4000 mg
      Liver toxicity, sedation, dependenceDimes
       Other prescription agents
        4% Lidocaine aqueous solution for nasal instillation0.5 mL to nostril(s) on side of pain over 30 s, repeat after 2 min if neededUncertainLocal burningDimes
        Ergotamine, 1 mg with caffeine. 100-mgoral tablets2, then 1 every 30 min 4 times6 tablets/24 h; 10/wkNausea, vasoconstriclion, fetal harmS0.50-S0.75
        Ergotamine, 2 mg with caffeine. 100-mg suppository1 rectally every hour for 2 h or until headache is gone2 suppositories/24 h; 5/wkNausea, vasoconstriction, fetal harm$5
        Ergotamine, 2-mg tablets SLL SL every 30 min, 3 times3 tablets/24 h; 5/wkNausea, vasoconstriction, fetal harm$5
       Parenleral agents
        Dihydroergotamine, 1 mg/mL for injection0.5–1 mg IM, SC, or IV every hour for 3 h3 mgNausea, vasoconstriction$10-$15
      For drug, not for administration.
        Dihydroergotamine, 0.5 mg/mL nasal spray0.5-mg spray in each nostril, repeat in 15 min3 mg (6 sprays)Nausea, vasoconstriction$15-$20
      For drug, not for administration.
        Ketorolac15–30 mg IM or IV every 6 h or30 mg (if 65 y) or 60 mg (if<65 y)If<65 y, 120 mg If 65 y, 60 mgGI upset, renal toxicity$10
      For drug, not for administration.
        Meperidine or alternative narcotic analgesic; often used with an adjuvant50–150 mg 1 M or SC every 4 h400 mgDrowsiness, respiratory depression, nausea, dependence$1
      For drug, not for administration.
      Selective 5-HT1 agonists
        SumatriplanAusoinjeclor, 6 mgj: SC every hour or longer12 mgChest or neck discomfort$40-$50
        SumatriptanNasal spray, 5 mg or 20 mg
      Optimal dose.
      every 2 h or longer
      40 mgChest or neck discomfort$15-$20
        SumatriptanTablet, 25 mg or 50 mg
      Optimal dose.
      every 2 h or longer
      300 mgChest or neck discomfort$15
        NaratriptanTablet, 1 mg or 2.5 mg
      Optimal dose.
      every 4 h or longer
      5 mgChest or neck discomfort$15
        RizatriptanRegular or oral-dissolving tablet, 5 mg or 10 mg
      Optimal dose.
      Usc 5-mg dose if patient is taking propranolol.
      every 2 h or longer
      30 mgChest or neck discomfort$15
        ZolmitriptanTablet, 2.5 mg
      Optimal dose.
      or 5 mg every 2 h or longer
      10 mgChest or neck discomfort$15
      Preventive antimigraine therapy
       β-Adrcnergic blockcrs
      Others can be used.
        Propranolol40–320 mg/d320 mgBronchospasm, bradycardia, hypotension, fatigue, depression$10-$80
      Average cost per month.
      (generic)
        Timolot10–30 mg/d30 mgBronchospasm, bradycardia, hypotension, fatigue, depression$ 15-S30
      Average cost per month.
      (generic)
       Calcium channel blocker
      Diltiazem can be used.
        Vcrapamil240–480 mg/d480 mgHypotension, constipation, edema$20-$70
      Average cost per month.
      (generic)
       Tricyclic antideprcssant
      Others can be used.
      ?
        Amitriptyline10–150 mg/d150 mgSedation, dry mouth, weight gain, tremor, cardiac arrhythmias, difficulty voiding$2-$8
      Average cost per month.
      (generic)
       Anticonvulsant
        Divalproex sodium250–1500 mg/d1500 mgNausea, fatigue, weight gain, hair loss, tremor, liver toxicity, fetal harm$25-$125
      Average cost per month.
      * GI = gastrointestinal; 5-HT1 = serotonin (5-hydroxylryplamine1); 1 M = intramuscularly; IV = intravenously; OTC = over-the-counter; SC = subcutarieously; SL = sublingually.
      For drug, not for administration.
      Optimal dose.
      § Usc 5-mg dose if patient is taking propranolol.
      // Others can be used.
      Average cost per month.
      # Diltiazem can be used.
      Although in general “stronger” medications are needed for severe migraine attacks, many attacks can be controlled with simple analgesics, especially if taken promptly. The choice of medication will be based on the patient's previous experience, the severity and duration of the headache and any associated symptoms, the frequency of the attacks, the patient's desire to avoid characteristic adverse effects, comorbid conditions, cost, and the clinician's experience. Experimentation with a medication may be necessary to determine an effective dose that does not produce excessive adverse effects.
      • Capobianco DJ
      • Cheshire WP
      • Campbell JK
      An overview of the diagnosis and pharmacologie treatment of migraine.
      Some patients use a staged approach for headache treatment in which they start with a weaker medication and use more potent drugs later during the attack if needed. Some patients use a stratified approach in which they choose among several treatment options, depending on the severity of the attack. Other patients prefer to take the best medication for all attacks. Evidence-based practice guidelines for the treatment of migraine have been published.
      • Institute for Clinical Systems Integration
      Health Care Guideline: Migraine Headache.
      • Prysc-Phillips WEM
      • Dodick DW
      • Edmeads JG
      • et al.
      Canadian Headache Society. Guidelines for the diagnosis and management of migraine in clinical practice [published correction appears in CMAJ. 1997;157:1354].
      Single-ingredient, over-the-counter analgesics (acetaminophen, aspirin, ibuprofen, and naproxen sodium) can be useful for mild to moderate headaches. The nonsteroidal anti-inflammatory drugs in this group can increase the nausea that usually accompanies migraine attacks. Combination over-the-counter analgesics containing caffeine and aspirin with or without acetaminophen are helpful, but caffeine-containing medications promote the occurrence of rebound headache (see subsequent discussion).
      Multiple prescription analgesic/antimigraine preparations are available. Many are combination medications that can lead to rebound headache.
      • Silberstein SD
      • Lipton RB
      • Goadsby PJ
      • Malhew NT
      • Kurman R
      • Perez F
      Drag induced refractory headache-clinical features and management.
      Some of these medications are formulated specifically for migraine (such as a combination of acetaminophen, isometheptene, and dichloralphenazone or ergotamine tartrate and caffeine), whereas others are pure analgesics. Many contain controlled substances (butalbital, codeine, and propoxyphene napsylate). A few of the medications are available as suppositories (ergotamine tartrate and caffeine). Several analgesics are available by injection (codeine, ketorolac, and meperidine).
      For severe nausea accompanying a migraine attack, prochlorperazine, chlorpromazine, and metoclopramide can be useful adjuncts. Metoclopramide can increase the bioavailability of analgesic agents by enhancing gastric motility and gastrointestinal absorption.
      The benefit of 4% lidocaine aqueous solution nose drops has not been as substantial as was initially suggested. Nonetheless, lidocaine nose drops are exceedingly safe, reportedly fast-acting, inexpensive, compatible with all other migraine medications, and helpful for a minority of patients.
      Parenteral dihydroergotamine (DHE) has been available for more than 50 years. In recent years, DHE has gained wider use for acute treatment of individual migraine attacks, to help break up a single prolonged migraine attack, and to help a patient through withdrawal from a medication causing rebound headache. Unlike ergotamine, DHE does not seem to promote chronic daily headache and is less likely to cause arterial constriction. In 1998, a nasal spray formulation of DHE was approved by the Food and Drug Administration for acute migraine attacks. The DHE nasal spray is somewhat cumbersome to use because the sprayer must be filled at the time of administration, and sprays to both nostrils must be delivered twice, 15 minutes apart. Like ergotamine, DHE can increase nausea. DHE can also be prescribed for self-injection (0.5 mg or 1 mg intramuscularly or subcutaneously approximately every hour, with a maximum of 3 mg in 24 hours). DHE is contraindicated in patients with peripheral or coronary artery disease, those with uncontrolled hypertension, and women who are pregnant or nursing.
      The development of selective serotonin (5-hydroxytryptamine1 [5-HT1] receptor) agonists has been a genuine breakthrough in the treatment of migraine headaches. These medications reverse the pain and nausea of migraine without clouding the sensorium and are not habit-forming. They can be .helpful even if administered well after the onset of headache. If the initial dose is helpful but the headache recurs or worsens, additional doses of the 5-HT1 agonist may augment the benefit or completely eliminate the migraine headache. The benefit is sustained over time.
      The 4 selective 5-HT1 agonists now available are sumatriptan, zolmitriptan, naratriptan, and rizatriptan. All are available as tablets; sumatriptan is also available as an autoinjector and a nasal spray, and rizatriptan is also available as an oral-dissolving tablet. Sumatriptan by injection acts more rapidly than sumatriptan nasal spray, which works quicker than rizatriptan, which works quicker than the other 2 available “triptans.” Naratriptan has the slowest onset of action and the longest half-life. DHE also has a relatively long half-life. Therefore, for patients with rapidonset migraine attacks, sumatriptan by injection or by nasal spray or rizatriptan is more likely to be effective. For patients with long-duration migraine attacks or those in whom the other medications provide only temporary relief, naratriptan or DHE might be more effective for reducing the risk of headache recurrence. If the patient experiences vomiting early during the migraine attack, sumatriptan by injection or by nasal spray, DHE by injection or by nasal spray, or the oral-dissolving rizatriptan tablet should be considered. Sumatriptan nasal spray and DHE are more likely than the other 5-HT 1 agonists to cause nausea. If the patient does not respond to one triptan, a different one may be effective.
      The triptans can cause chest and neck pressure and myocardial ischemia, usually in patients with underlying coronary artery disease. With sumatriptan, which has been in use the longest, the estimated risk of a myocardial infarction occurring is 1 in 1 million people, and deaths have been reported. Chest pressure is most likely to occur with sumatriptan by injection. Naratriptan has the lowest reported incidence of chest discomfort. Patients with or at risk of coronary artery disease should not take the triptans. If a triptan is given to such a patient, a test dose under medical surveillance is recommended. The triptans, OHE, and ergotamine should not be given within 24 hours of each other.
      Contraindications to 5-HT1 agonist therapy include known or suspected ischemic heart disease, Prinzmetal angina, uncontrolled hypertension, recent monoamine oxidase inhibitor therapy, severe liver disease, and hemiplegic or basilar migraine in which severe or prolonged neurologic deficits accompany the headache. The safety of the triptans during pregnancy is unclear, and the potential benefit must be weighed against an uncertain, probably low risk. Fortunately, migraine attacks usually diminish during pregnancy.
      Treatment of acute migraine attacks in patients at urgent care centers and emergency departments with parenteral medications, such as DHE, ketorolac, or meperidine, is expensive. The use of meperidine should be restricted to patients who have infrequent severe attacks that do not respond to other antimigraine medications or to those in whom the other antimigraine medications are contraindicated.
      • Welch KMA
      Drug therapy of migraine.
      Patients can be instructed in self-administration of DHE.
      • Welch KMA
      Drug therapy of migraine.
      • Capobianco DJ
      • Cheshire WP
      • Campbell JK
      An overview of the diagnosis and pharmacologie treatment of migraine.

      Menstruation-Associated Migraine

      Many women are likely to experience migraine during menses, and a few report migraine attacks exclusively during the perimenstrual period.
      • Olesen J
      • Tfelt-Hanscn P
      • Welch KMA
      • et al.
      • Silberstein SD
      • Lipton RB
      • Goadsby PJ
      Menstruation-associated migraine can be difficult to treat. Any of the medications listed in Table 3 can be used for menstruation-associated migraine. In particular, the 5-HT1 agonists are beneficial. Continuous preventive antimigraine therapy can be used if warranted based on the woman's complete headache history. If the woman's headaches are exclusively or primarily limited to menses and her menstrual cycle is regular, preventive medications can be used for a few days before and during menstruation. Nonsteroidal anti-inflammatory drugs (eg, naproxen sodium 550 mg twice a day) have been most commonly used in this setting, but other standard preventive medications (see subsequent discussion) can also be used. Ergotamine tartrate (1 tablet twice a day or half a suppository daily at bedtime) or sumatriptan (25 mg 3 times a day) has also been used for the few days before and at the start of menses in an effort to prevent expected migraine attacks.

      Prolonged Migraine Attack

      For patients with severe, prolonged migraine attacks (greater than 72 hours), treatment with intravenous fluids, parenteral antimigraine medications, parenteral antinauseants, and, possibly, corticosteroids should be considered. Repeated doses of DHE, 0.5 to 1 mg intravenously, intramuscularly, or subcutaneously every 8 hours, usually in combination with metoclopramide or an alternative antinauseant, are commonly recommended.1,3,5–7 For pain relief, ketorolac can be given, 15 to 30 mg intramuscularly or intravenously every 6 hours (not to exceed 120 mg in 24 hours) or a single dose of 30 to 60 mg, or meperidine can be used, 50 to 150 mg intramuscularly or subcutaneously every 4 hours. For nausea, the choices are metoclopramide, 5 to 10 mg intravenously; prochlorperazine, 5 to 10 mg intramuscularly or intravenously or up to 25 mg rectally; or chlorpromazine, 25 to 50 mg intramuscularly or 50 to 100 mg rectally. To stop a prolonged migraine headache, corticosteroid use is empirically justified as a “last resort”: dexamethasone, 4 to 20 mg/d; hydrocortisone, 100 to 250 mg/d; prednisone, 40 to 100 mg/d; or methylprednisolone, 40 to 100 mg/d can be given for several days.
      • Institute for Clinical Systems Integration
      Health Care Guideline: Migraine Headache.
      • Silberstein SD
      • Lipton RB
      • Goadsby PJ

      Transformed Migraine And Chronic Daily Headache

      Regular use of almost any migraine medication can lead to increasingly frequent headaches.
      • Silberstein SD
      • Lipton RB
      • Goadsby PJ
      • Malhew NT
      • Kurman R
      • Perez F
      Drag induced refractory headache-clinical features and management.
      The headaches can occur daily and are related to rebound withdrawal from frequent use of the antimigraine medication. Patients experiencing this phenomenon are said to have transformed migraine and often experience episodic migraine attacks superimposed on their daily headache. The combination over-the-counter analgesics, combination prescription an algesics, narcotic-containing analgesics, and ergotamine-containing medications are especially prone to promote the development of chronic daily headache. Caffeine alone can cause a similar clinical picture. Experience with the triptans tans is limited; sumatriptan has been reported to cause rebound-withdrawal headaches. DHE rarely, if ever, leads to rebound headaches.
      When patients are experiencing chronic daily headache due to rebound withdrawal, they do not usually respond to other acute or any preventive medications. Attempts to discontinue the medication that causes rebound withdrawal result in increased headache. Therefore, preventing the development of transformed migraine and chronic daily headache is preferable. The medications that are especially prone to cause transformed migraine are acceptable for occasional use—ie, the patient has 2 or fewer headaches per month. However, if the patient experiences migraine more frequently, use of single-ingredient, over-the-counter or prescription medications or several medications on a rotating basis is recommended; the patient should be instructed to not use any single medication, including triptans, more than 2 days per week.

      Preventive Antimigraine Therapy

      Another approach to treating migraine is the regular use of medications intended to prevent the occurrence of individual migraine attacks and to reduce their intensity and duration. Although an occasional patient will experience dramatic improvement with prophylactic medications, a more realistic expectation is a 50% reduction in headache symptoms. The patient's migraine symptoms must be severe enough to justify the use of daily preventive medications. Suggested criteria include (1) patient has 6 or more headache days per month, (2) symptomatic medications are contraindicated or ineffective, (3) medication is necessary more than twice a week, or (4) there is a great need to prevent infrequent migraine attacks, including hemiplegic migraine, those producing profound disruption, or those associated with a risk of stroke.
      • Silberstein SD
      • Lipton RB
      • Goadsby PJ
      Ultimately, the patient makes the decision whether to use preventive medications.
      For practical purposes, 6 types of medication can be considered for preventive antimigraine therapy
      • New “triptans” and other drugs for migraine
      • Ramadan NM
      • Schultz LL
      • Gilkey SJ
      Migraine prophylactic drugs: proof of efficacy, utilization and cost.
      ; the 4 most commonly used are shown in Table 3. The doseresponse relationships vary. Usually, the initial dose is low, and the dose is gradually increased as needed and tolerated. Patients need to take the preventive medications for at least 2 to 3 weeks before a benefit is noted, and the maximal beneficial effect can take as long as 8 to 12 weeks to occur. A preventive agent is chosen based on its potential effect on other medical conditions the patient has and the desire to avoid characteristic adverse effects associated with each medication.
      The β-adrenergic blocking drugs that are used are propranolol, timolol, atenolol, metoprolol, and nadolol. One β-blocker may fail, and another may be effective. Adverse effects include aggravation of asthma, bradycardia, hypotension, fatigue, depression, and masking of the symptoms of hypoglycemia. Calcium channel blockers are used, generally verapamil and occasionally diltiazem. Adverse effects include hypotension, constipation, and peripheral edema.
      Tricyclic antidepressants can be used to prevent migraine and treat tension-type headache, chronic daily headache, and other chronic pain states. Although amitriptyline has been the most studied, nortriptyline has fewer adverse effects. Other tricyclic agents have not been studied but are probably effective. Adverse effects include sedation, dry mouth, weight gain, tremor, cardiac arrhythmias, aggravation of angle-closure glaucoma, and difficulty in urinating. Clinicians should note that the newer selective serotonin reuptake inhibitor-type antidepressants are not recommended for the prevention of migraine headaches.
      A single anticonvulsant, divalproex sodium, has been shown to be an effective preventive agent for migraine and can decrease chronic daily headache as well. Adverse effects include nausea, fatigue, weight gain, hair loss, tremor, liver dysfunction, and neural tube defects in developing embryos.
      Taken regularly, several nonsteroidal anti-inflammatory drugs, including naproxen, aspirin, tolfenamic acid, flurbiprofen, and fenoprofen, have been shown to help prevent migraine. Adverse effects include gastrointestinal upset, mild bleeding tendency, and renal dysfunction.
      Because of potentially serious adverse effects, methysergide is uncommonly used to prevent migraine, even though it is effective. Adverse effects include weight gain, muscle cramps, vasoconstriction, and, most worrisome, retroperitoneal, pleuropericardial, and subendocardial fibrosis, which occurs with prolonged use. Therefore, pa tients should take methysergide continually for no more than 5 to 6 months, followed by a 1-month drug holiday. Patients taking methysergide should not take 5-HT
      • Olesen J
      • Tfelt-Hanscn P
      • Welch KMA
      • et al.
      agonists, DRE, or ergotamine for acute migraine headaches.
      In general, 1 preventive medication is used at a time. The combination of a tricyclic agent and a β-blocker or calcium channel blocker has been recommended for patients with refractory migraine.
      • Capobianco DJ
      • Cheshire WP
      • Campbell JK
      An overview of the diagnosis and pharmacologie treatment of migraine.
      • Silberstein SD
      • Lipton RB
      • Goadsby PJ
      Preventive medications are usually given for 6 to 12 months, at which time the need for continuing the medication is reassessed.

      Conclusion

      Effective therapy is now available for migraine headaches, which are a common cause of short-term pain. Migraine is underdiagnosed and often undertreated. Some patients can benefit from the recognition and elimination of factors that trigger their migraine headaches. Treating the individual acute migraine attacks promptly is the optimal strategy for most patients. A wide variety of medications can be helpful when given early during the course of the migraine. Patients and their health care providers may need to experiment to find optimal medications and dosages. For patients with frequent, severe migraine attacks that do not respond adequately to acute treatment, regular use of 1 of several preventive antimigraine medications should be considered.

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        • Tfelt-Hanscn P
        • Welch KMA
        • et al.
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