Evaluation and Management of Migraine in the Emergency Department
Author: Eric Davis, MD, Associate Professor of Emergency Medicine, University of Rochester College of Medicine and Dentistry, Director, Urgent Care, Strong Memorial Hospital, Rochester, NY.
Peer Reviewer: Larry B. Mellick, MD, MS, FAAP, FACEP, Professor, Department of Emergency Medicine and Pediatrics, Residency Program Director, Department of Emergency Medicine, Medical College of Georgia, Augusta.
Many of the patients I see in the emergency department use the term "migraine" to describe their symptoms. There may be different reasons for that. Some patients may think that migraine is synonymous with headache. Others may think that using the term migraine may get them more rapid or stronger pain treatment.
As a resident (now about 30 years ago!), I dreaded picking up a patient ED chart and seeing a triage complaint of "migraine." I knew that the patient would often be unhappy and usually would leave dissatisfied with my treatment. Since then, much has changed. There is now better understanding of the migraine process and much better treatment.
I have learned and now welcome the triage complaint of "migraine." I can explain to patients why they hurt. I can provide specific treatment. And I can give the patient instructions on how to deal with future episodes.
I found this issue of Emergency Medicine Reports to be very useful in my practice. I trust you will, too.
J. Stephan Stapczynski, MD, FACEP, FAAEM, Editor
Introduction
Patients experience headache more than any other form of pain. Headaches account for more than 10 million physician visits annually, including 0.5-2.7% of emergency department (ED) visits.1-4 Headaches can be divided into 2 groupsprimary and secondary. Primary headaches are classified as migraine, cluster, or tension, with secondary headaches consisting of all other types.5 In patients presenting to the ED with head pain, primary headaches represent 81.2 %.2,6,7 One-third of these are migraines.2 The population incidence of migraine is approximately 18% in females, and 6% of males8,9 with an estimated 23-28 million Americans suffering from severe disease.3,10 This makes the prevalence of migraine equal to that of asthma and diabetes combined. Whites are affected more than other racial sub-types, and prevalence is inversely related to household income, a population that often utilizes the ED for their medical care. The prevalence is highest in the 25- to 55-year-old age group.11,12 This greatly affects work productivity, with estimated direct cost of more than $1 billion, and indirect costs of $11-50 billion8,11 due to absenteeism and decreased productivity. The World Health Organization ranks migraine headache as one of the most disabling chronic medical disorders.
Despite the commonality of migraine headaches, they remain misunderstood and inappropriately treated. Population-based studies have shown that only 50% of patients meeting the International Headache Criteria (IHC) for migraine have an official diagnosis;13 among those patients seen in the ED with a prior diagnosis, only 45% met formal criteria, and of those with a discharge diagnosis of migraine, 56% were deemed appropriate,14 and 31% had never seen a physician for their headaches.12 Those patients who have seen an office-based physician for their migraine are satisfied with their care less than 50% of the time.14-17 Those who are not seeing a physician regularly for treatment of their migraine are more likely to use the ED for their care. Only 23-50% of those who carry the diagnosis take prescription medications for migraine,12,18 despite increasing numbers of effective treatments. Migraine-specific treatments have been shown to improve quality of life and decrease job absenteeism.19-21 This form of treatment is not always utilized in the ED, where it is more common to treat patients with migraine with nonspecific medications such as opiates8,22 or antiemetics,3 with triptan use ranging from 2-41%.3,8 It is important for the ED physician to understand proper treatment of the acute migraine to both maximize benefit and prevent unwarranted outcomes.
Pathophysiology
The pathophysiology of migraine genesis is complex, and while understanding of it has improved in recent years it is still not completely understood. The past explanation that migraines are purely a vascular phenomenon related to first vasoconstriction and decreased oxygenation followed by vasodilatation and pain is no longer accepted.23-26 Current evidence supports that migraines originate from disturbances in the central nervous system,7 which lead secondarily to vascular changes. Primary stressors cause release of inflammatory substances, which lead to dilatation of meningeal blood vessels resulting in pain, further nerve activation, and inflammation.24,25,27 This results from dysfunction of brain stem diencephalic nuclei that are responsible for sensory (especially nonciceptive) modulation of craniovascular efferents.23,25,28 The trigeminal nerve is also involved.7,24 Sensitization usually progresses from peripheral to central, and as central sensitization develops, cutaneous allodynia (pain in the skin initiated by a stimulus that is not normally painful) develops.29 Treatment is much more effective when initiated prior to this event.30,31 The pain is thus secondary to both altered perception (central and peripheral) of stimuli that do not normally cause pain as well as activation of an afferent forward neurovascular dilator mechanism in the ophthalmic branch of the trigeminal nerve.23,25,32 The trigeminal nerve, notably the first (ophthalmic) branch, is an important factor.33 Pain impulses are carried along the nerve through nociceptive tracts, which leads to sensitization of second and third order neurons, including innervation of intracranial blood vessels and meninges.34 Recruitment of other neurons through convergence in the dorsal horn and trigeminal caudate nucleus occurs, which may be responsible for the occipital and cervical pain seen in migraine. This complex cascade of events helps to explain the fact that no one treatment is successful in treating all migraines, as well as establishing new potential methods for treatment with existing as well as future medication.35-37
The Convergence Hypothesis. A clinical view of the most commonly seen patient presentations of primary headache disorders that integrates the current understanding of migraine pathophysiology has been put forward as the convergence hypothesis.38 Convergence states that there is likely one underlying clinical process for primary headache and specifically views the clinical entities of migraine, migrainous, and tension-type headache as resulting from the same underlying pathophysiologic process. Because the only tool we have to formulate the clinical diagnosis of primary headache types is the clinical history, convergence states that the clinical diagnosis depends on how far the headache process progresses before being terminated by the brain's normal homeostatic mechanisms and what level of the trigeminal system is activated. (See Figure 1.) It seems likely that for the primary headache sufferer there is an inherent sensitivity of the brain to changes, internal and external, and that the ability of the brain to regulate the response to these changes is less effective than the brain of a person who does not have headache. Because headache is a nearly universal human experience, it seems likely that any brain can experience the clinical phenomenon of headache if the right set of circumstances exists. A likely extension of the convergence hypothesis is that this inherent brainstem syndrome can be initiated from various levels and can produce the entire spectrum of headache syndromes discussed in this article.
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There is clearly a genetic component to migraine with a well demonstrated familial association.29,39 Most migraine syndromes are probably polygenic and thus multifactorial39 with the noted exception of familial hemiplegic migraine.36 This may contribute to the difficulty in finding universally effective therapy as well as explaining individuals' non-uniform responses to treatment.
Diagnosis
Migraine headache complaint is common in patients presenting to the ED, yet it remains under-diagnosed. Population-based studies have shown that only 48% of patients meeting the criteria for migraine headache carry a formal diagnosis.7,22 A basic understanding of diagnostic criteria will help the emergency physician both to accurately diagnose and to refer appropriate patients for specific migraine therapy. The most commonly used criteria are from the International Headache Society (IHS)40 and are presented in Tables 1 and 2; however, it is important that the emergency physician first determine that no life-threatening cause for the headache is present. Danger signals or "red flags" of secondary headaches that may represent intracranial pathology include sudden onset of new, severe headache, headache progression in severity, onset with exertion or sexual activity, onset later than middle age, headache with alteration in level of consciousness, meningeal signs, headache with abnormal vital signs including fever, failure of symptomatology to fit a benign profile,3,22,28,41,42 abnormal neurological findings,21 history of seizure, occipitonuchal location,41,42 or increase with valsalva.21 Somewhat surprisingly, headache type, severity, characteristics, or duration of pain did not correlate with abnormalities on neuroimaging.43 Absence of these factors and a headache profile that fits the IHS criteria make a presumptive diagnosis of migraine probable. Migraine screening tools may also be of help.44,45
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In 50-80% of patients with migraine, the headache is preceded by premonitory symptoms occurring hours to days prior to the onset of pain.10 These symptoms are commonly osmophobia (sensitivity to odors), photophobia, phonophobia, yawning, drowsiness, irritability, euphoria, fluid retention, thirst, polyuria, and food cravings.10 These may or may not be recognized by the patient. Those with a consistent association may seek treatment with symptom onset prior to the actual headache. Ten to twenty percent of migraines experience an aura, which usually lasts 10-30 minutes but may last up to an hour.10,11 Visual disturbances are the most common, with less common symptoms of numbness/tingling, motor disturbances (monoparesis or hemiparesis), cognitive impairment, or language disorders.10 In children, aura can manifest itself as an acute confusional state.10 These symptoms abate with the onset of pain. The pain of migraine is usually pulsatile in character but may be constant and non-pulsatile. In 60 % of patients the pain will be unilateral with the remainder bilateral.9 Onset is usually gradual and the total duration is 4-72 hours in most cases, although severe migraine or status migrainosus can last much longer (up to 8 days).
Associated findings along with pain are almost universal photosensitivity (90%) and phonosensitivity (76%), due to sensitivity of cranial afferents during an attack.5 Phonophobia is more specific to migraine.46 Nausea(70%) and vomiting (29-40%) are also common and are often rated by patients as being as incapacitating as the pain itself.29 Other less common associations include anorexia, osmophobia, blurred vision, skin pallor, inability to concentrate, light headedness, and nasal congestion.
Treatment
Migraine therapy consists of three separate typesnonpharmacologic, abortive, and preventive. While emergency physicians should be most familiar with abortive medication therapy, they should be aware of other phases of migraine treatment to provide the best overall care for patients.
Nonpharmacologic. Patients diagnosed with migraine are often undereducated about their condition. It is important to discuss the nature of the disorder, including explaining that it is not life-threatening but a chronic, relapsing disease, so that realistic expectations can be set. A good way to explain it in lay terms is that patients have a sensitive neurovascular system that overreacts to internal changes or external stimuli.10,11 There are therapies that lessen the severity of migraine headaches, and the patient needs to be an active participant in treatment, which has shown to improve response.
The next step is to identify potential triggers for migraine. Multiple factors have been implicated. (See Table 3.) A headache diary can help to identify the causal agent, and patients should be encouraged to record events in temporal relation to the migraine onset. While this is a recommended step, it should be noted that most migraines are not associated with an identifiable trigger. Wellness programs and such basic interventions as regular meals, adequate sleep, and exercise have also been demonstrated to improve outcome.10,47 Weather changes, which frequently have been cited as a trigger, apparently do not cause migraine.26
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Abortive Therapy. While non-pharmacologic intervention may help prevent or lessen migraine severity, most patients will need pharmacologic treatment at some point.7 There are multiple medications that can be used to treat an acute migraine headache. Table 4 outlines the recommendations of the U.S. Headache Consortium and the AAFP/ACP-ASIM. Table 5 is from the Canadian Medical Association with recommendations for treatment of severe and ultra-severe attacks. Each class of medication will be discussed separately. Certain general principles should be noted, however. Patients should be placed in a dark quiet environment with external stimuli as limited as possible.11 For medication administration, two types of approaches to acute migraine therapy have been testedstep care vs. stratified care. In step care, treatment is based on starting with a first line of medication and progressing with more potent drugs until relief is obtained, while stratified care seeks to match the initial medication treatment to the severity of the attack. Studies have found that the stratified approach is superior15,41,48 and is the preferred method. Effective migraine therapy also can vary among patients48 and it is prudent to inquire what has worked on prior headaches for the individual. Earlier treatment is better, especially when utilizing ergots or triptans.30,49 Response to triptans or ergots is also not diagnostic of migraine headache and as such does not rule out a more serious cause of headache.23 Women of child-bearing age must always be asked about the potential of pregnancy as most treatments can be harmful to the fetus, including preterm labor for triptans and congenital abnormalities with ergots.10,24 Finally, overuse of symptomatic medications can lead to rebound headaches and eventually to chronic daily headache, which may necessitate special treatment. Return of headache after initial response to therapy is also common and must be taken into consideration when discharging patients.1,3,6,10,13,50
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NSAIDs, Nonopiate Analgesics, and Combination Analgesics. Generally, studies support the effectiveness of this class of pain medication, especially in mild to moderate attacks and they are recommended as first-line agents.10,13,14,51 Naproxen, ibuprofen, and aspirin may have some advantage over other NSAIDs,15 and indomethacin suppositories are useful in patients with nausea and vomiting.10 This class may also be helpful in severe attacks that have previously responded to them.13 Combining NSAIDs with antiemetics14 or sumatriptan42 may show a synergistic effect, and use in combination with opiates may decrease the effective narcotic dose. The combination agent of acetaminophen and aspirin and caffeine is also considered a first-line agent,51 but acetaminophen alone is ineffective.13,14,52
Antiemetics. Antiemetics serve a dual role in the treatment of migraine headaches. As nausea and vomiting are common in migraine attacks, and may be as debilitating as the headache pain, liberal use is recommended. As gastric atony is common in migraine attacks, the use of an antiemetic that enhances gastric motility, such as metoclopramide, may be a helpful adjunct to improve absorption when oral medications are used. Used alone, the antiemetics with dopamine antagonism have shown efficacy.
In addition to their relief of nause and vomiting, antiemetics with dopamine antagonism appear to have specific anti-migraine activity. The three agents that have been most studied are droperidol, metochlopramide, and prochlorperazine. Droperidol has been studied in several clinical trials, using initial doses of 5 mg IM or 2.5 mg IV.53-56 Effective relief in pain and other symptoms have been observed in 80-90% of patients within 1 hour, although some patients may require additional doses. Depending on the severity and duration of the migraine episode, recurrence of symptoms may be seen in 10-24%.
Metoclopramide also may have utility as a primary agent.40,50 In one study it was found to be equal to a single 6 mg SQ dose of sumatriptan in a dose of 20 mg IV with up to 4 doses.57 Prochlorperazine has been shown to be superior to metoclopramide when using the IV or IM route.39,58 In one study 88% had complete or partial relief when it was used as a single agent.37 Chlorpromazine may also have benefit.51 Incidence of adverse events was similar with all types; drowsiness was the most common with a lower incidence of dystonia and akasthesia.32 It should also be noted that the use of antiemetics by the parental route was found to be 3.5 times as effective in alleviating headache pain relative to the agents patients can take at home,3 so utilizing the same agent by a different route may improve efficacy.
Triptans (Serotonin 5 HT Agonists). The development of triptans for the treatment of migraines has been a major therapeutic breakthrough. There are five currently in clinical use: sumatriptan, naratriptan, rizatriptan, zolmitriptan, and almotriptan, with only sumatriptan available for parenteral administration. They are classified as migraine-specific treatments, although evidence exists that they can be effective in all primary undifferentiated headaches.59,60 Onset of action is fastest with sumatriptan 6 mg SQ injection11,13 with naratriptan slowest but having the longest half-life, which may help to prevent recurrence headaches.61 Recurrence of the migraine pain after a pain-free interval has been seen in 17-40% of headaches,10,61 with the initial efficacy (2 hours) ranging from 24-76%.62 Early administration is very important as treatment at the onset of pain when the headache is mild is far more effective11,49,62 especially prior to development of cutaneous allodynia, usually within 2-4 hours.30 Early administration also decreases the rate of recurrence when the headache is mild.57 Side effects include tingling, paresthesias, dizziness, and flushing, which for the most part are well tolerated. Contraindications to administration include inadequately controlled hypertension, ischemic heart disease, complicated migraine, MAOI use, and pregnancy. It is also recommended to be cautious with use in patients thought to be at risk for coronary artery disease.
Ergot Derivatives. This class of medication, which includes the ergots and dihydroergotamine (DHE), was the first migraine-specific treatment discovered. DHE has largely replaced ergotamine in use due to its improved efficacy in constriction of peripheral arteries and lack of physical dependence.10,13 A review of the use of parenteral DHE for acute migraine headache concluded that the data show that it is not as effective as sumatriptan or phenothiazines as a single agent; if administered with an antiemetic, however, it was as effective as opiates, ketorolac, or valproate.36,40,63,64 With the advent of triptans, their use is now mostly confined to the treatment of intractable migraine and status migrainosus.10,15 Both types cause nausea and should be given with an antiemetic, preferably metoclopramide or prochlorperazine. Side effects may also include paresthesias and abdominal cramping.10 Contraindications to their use include pregnancy or consideration of pregnancy, poorly controlled hypertension, sepsis, vascular disease, and hepatic or renal insufficiency. Any patient experiencing chest tightness with use should be worked up for coronary artery disease.10
Opiates. The use of opiates for treatment of migraine headache is controversial. While some ED studies have shown that they are the most commonly administered agent,8,22 most guidelines urge caution with their routine and especially first-line use.10,15,23 Some research has suggested that opiates may not be the most effective migraine treatment.5,13 Other concerns include over-sedation, addiction, and overuse rate;19 this, however, may not be applicable in an ED population.13 The general consensus is that opiates may have utility as breakthrough or rescue medications when other concerns have been addressed.5,13,15,19,23 The only well studied application is intranasal butorphanol which had good efficacy.13,51 Methadone has also been suggested as a treatment for status migrainosus due to the long half life.22 It should be noted that due to central changes in pain receptors that occur during migraine, higher than usual dosage of opiates may be needed.
Other Agents. A variety of other medications have been touted as effective treatments. While commonly used, barbiturates are not recommended for general use.15,52 Steroids (i.e., dexamethasone or hydrocortisone) do not have adequate studies to support or refute their efficacy but are recommended for status migrainosus.10,52 Intravenous valproate was shown in a single study to provide significant improvement in pain, nausea, and disability after 300 mg IV over 10 minutes.65 Botox injections have shown some promise.18 In a retrospective review of lower cervical injections with 0.5% bupivacaine, a demonstrated benefit of 85.4% of complete or partial relief was found.52
Severe, Ultra-Severe Attacks, and Status Migrainosus. While the standard treatment for migraine guidelines are for primary care physicians and patients with the entire spectrum of migraine, certain patients may present to the ED with migraines at the severe end of the spectrum. It is difficult to determine what intervention will be beneficial, so standard treatment should be employed for most patients. In the event that the normal treatment regimens are unsuccessful, the ED physician should consider moving to additional therapy. The Canadian Medical Association has published guidelines for this population as presented in Table 5 and included input from emergency physicians.32 Treatment should start with DHE IV, IM, or SQ, or sumatriptan orally or SQ. Intravenous metoclopramide should be administered if an IV is established. Hydration is also beneficial. If ineffective, 0.5-1.0 mg of DHE may be added IV to a maximum of 2 mg in 3 hours. An alternative is to give chlorpromazine 0 .1 mg/kg IV over 20 minutes, or prochlorperazine 25 mg rectally or 5-10 mg IV. If symptoms persist despite these treatments ketorolac IV or IM can be given. Dexamethasone 12-20 mg IV has been shown to be effective in some resistant cases. If all the above treatments fail, it may be necessary to employ opiates.
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The most severe form of migraine, which has been termed intractable migraine or status migrainosus, presents a unique challenge for the ED physician. This form of headache lasts greater than 72 hours and very often is resistant to multiple therapeutic interventions.7,11,66 It is recommended to treat these patients with DHE 0.5-1 mg IV, SQ, or IM along with metoclopramide.11,39,52 Additional medications, such as ketorolac or opiates, may need to be added. Therapy for this form of migraine is best accomplished as an inpatient with care managed by a clinician experienced in their administration. Other treatments such as adequate hydration, nutrition, and sleep must also be addressed.11
Preventive Therapy
While not in the normal scope of care for emergency medicine, practitioners should be aware that there are a number of therapies that have been shown to help prevent migraine attacks. In general, two-thirds will experience a reduction of 50% in headache frequency with prophylaxis.23 Beta-blockers, amitriptyline, divalproex sodium, and sodium valproate have shown efficacy14,15,45 for migraine alone, with amitriptyline best for mixed types. Effective dose and response to individual medication varies greatly and may take multiple changes in regimen to achieve the desired effect.18 Initiation of this form of treatment should be considered in patients experiencing greater than 6 headache days per month, if abortive medication is needed 2 or more times a week, if symptomatic medications are ineffective or contraindicated, or with high-risk migraines such as hemiplegic forms or migraine with prolonged aura.11,13,39 These patients, who are often frequent users of the ED, should be referred to a headache specialist. It has been estimated that only 5% of migraineurs are taking prophylactic therapy medication with a much higher percentage of potential candidates.12
Medication Overuse Headache
Medication overuse headache, also known as rebound headache or drug-induced headache, is a result of frequent use of acute or abortive medication that results in a cycle of increasing headache frequency, which, in its most severe form, results in chronic daily headaches. Initially described in the 1950s and well established in the 1980s,67,68 this disorder was first associated with opiates and ergots but is now recognized to occur with a wide variety of medications used to treat migraine.69 Classical features include headache that is refractory to treatment and occurs daily or near daily (> 15 days a month)70 occurring in patients with a primary headache disorder who use immediate relief medication frequently and often in excessive quantities. The headache varies in severity, type, and location; patients have a low threshold for pain induction; the headaches have a drug-dependent rhythmicity, and usually begins in the early morning (0200-0500). These headaches require progressively larger doses of analgesics, withdrawal symptoms are observed with cessation of pain medication, spontaneous improvement occurs with discontinuing of pain medications, and response to prophylactic medications is relatively ineffective.7,70,71 This patient population often uses medication on anticipation of headache. Diagnosis may be difficult and other more serious causes of headache may need to be evaluated. The development of these headaches may result after years of frequent analgesic use.35 If a patient of this nature is identified in the ED, usually because of frequent and/or escalating visits, it is important that the physician institute proper therapy and not perpetuate the problem by administering more frequent and higher doses of pain medication, usually opiates. Often, these patients are best treated in the inpatient setting under the care of a headache specialist. The first step is to discontinue all current pain medications including over-the-counter analgesics, opiates, sedatives, caffeine, ergotamine,11,71 and triptans.11,35 The recommended regimen is to then use DHE 0.5 mg (after a test dose at 1/3 strength) with 5-10 mg of IV metoclopramide every 6 hours for 48-72 hours.71 There is a 70-80% response rate to this regimen. Prophylactic medication may also be introduced at this time.
Summary
Headache is a common ED complaint. Of patients presenting with headache, over 25% are migraine in nature. New knowledge of the pathophysiology of migraine has changed our understanding of the cause, as well as treatment of this disorder. Emergency physicians should be aware of migraine-specific treatment to abort the acute attack, and should utilize care principles that match the medication used to the severity of the headache (stratified care). Opiates should not be utilized as a first-line agent, with interventions such as triptans, intravenous antiemetics such as prochlorperazine or metaclopramide, used primarily along with hydration in a dark, quiet room. Opiates may have utility as a rescue therapy. Severe attacks, especially those lasting more than 72 hours, need inpatient therapy with DHE or intravenous antiemetics. Finally, ED practitioners should be aware of red flags in the migraineur that may signal a more serious cause such as a sudden onset of a more severe or different headache, new neurological findings, increase in frequency or severity of attacks, fever or new meningeal signs, or onset with exertion. Most migraine patients should be referred to a headache specialist.
References
1. Miner J, Smith S, Moore J, et al. Sumatriptan for the treatment of undifferentiated primary headaches in the ED. Am J Emerg Med 2007;25:60-64.
2. Locker T, Manson S, Rigby A. Headache management-are we doing enough? An observational study of patients presenting with headache to the emergency department. Emerg Med Journal 2004;21:327-332.
3. Morgenstern L, Huber J, Lona-Gonzales H. Headache in the emergency department. Headache 2001;41:537-541.
4. International Headache Committee (IHC) ICD-10 guide for headaches. Cephalgia 1997; 17(Supp 19):115-127.
5. Ziegler DK. Opioids in headache treatment. Is there a role? Neurol Clin 1997;15:199-208.
6. Coppola M, Yealy D, Leibold R. Randomized, placebo-controlled evaluation of prochlorperazine vs metoclopramide for emergency department treatment of migraine headache. Ann Emerg Med 1995;26:541-546.
7. Villeneuve P, Szyszkowicz M, Steib D. Weather and emergency room visits for migraine headaches in Ottawa, Canada. Headache 2006;46:64-72.
8. Tepper S, Martin V, Burch S, et al. Acute headache treatments in patients with health care coverage: What prescriptions are doctors writing? Headache and Brain Diagnostic Challenges 2006;17:11-17.
9. Lipton R, Stewart W, Dramond S, et al. Prevalence and burden of migraine in the US: Data from the American migraine study II. Headache 2001;41:646-657.
10. Capobianco DJ, Cheshire WP, Campbell JK. An overview of the diagnosis and pharmacologic treatment of migraine. Mayo Clin Proc 1996;71:1055-1066.
11. Fiessler F, Kec R, Mandell M. Do ED patients with migraine headaches meet internationally accepted criteria? Am J EM 2002;20:618-623.
12. Silberstein S, Rosenberg J. Multispecialty consensus on diagnosis and treatment of headache. Neurology 2000;54:1553-1555.
13. Geraud G, Keywood C, Senard J. Migraine headache recurrence: Relationship to clinical, pharmacological, and pharmacokinetic properties of triptans. Headache 2003;43:376-388.
14. Snow V, Weiss K, Wall E, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Int Med 2002;137:840-849.
15. Lawrence E. Diagnosis and management of migraine headaches. South Med J 2004;97:1069-1077.
16. Capobianco D, Swanson V, Dodick D. Medication induced (analgesic rebound) headache: Historical aspects and initial descriptions of the North American experience. Headache 2001;41:500-502.
17. Lipton R. Stewart W, Stone A. Stratified care vs step care strategies for migraine the disability in strategies of care (DISC) study: A randomized trial. JAMA 2000;284:2599-2605.
18. Bartleson J. Treatment of migraine headache. Mayo Clin Proc 1999;74:702-708.
19. Lainez M, Lopez A, Pascual A. Effects on productivity and quality of life of rizatriptan for acute migraine: A workplace study. Headache 2005;45:883-890.
20. Weaver MB, Mackowiak JI, Solari PG. Triptan therapy impacts health and productivity. J Occ Environ Med 2004; 46:812-817.
21. Pransky G, Berndt E, Finkelstein S, et al. Performance decrements resulting from illness in the workplace: The effect of headaches. J Occ Environ Med 2005;47:34-40.
22. Vinson D. Treatment patterns of isolated benign headache in US emergency departments. Ann Emerg Med 2002;39: 215-222.
23. Goodsby P, Lipton R, Ferrari M .Drug therapy: Migraine current understanding and treatment. N Engl J Med 2002; 346:257-270.
24. Lipton R, Scher A, Kolodner K, et al. Migraine in the United States: Epidemiology and patterns of health care use. Neurology 2002;38:885-894.
25. Brandes JL. Treatment approaches to maximizing therapeutic response in migraine. Neurology 2003;61(Supp 4):S21-S26.
26. Silberstein S. Practice parameter: Evidence-based guidelines for migraine headache (an evidence based review). Neurology 2000;55:754-763.
27. Schreiber C. Pathophysiology of migraine. Clin Fam Pract 2005;7:407-421.
28. May A, Shepheard S, Wessing A, et al. Retinal plasma extravasation in animals but not humans: Implications for pathophysiology of migraine. Brain 1998;121:1231-1237.
29. Burstein R, Cutrer M, Yarnitsky D. The development of cutaneous allodynia during a migraine attack. Brain 2000;123: 1701-1709.
30. Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: A race against the development of cutaneous-allodynia. Ann Neurol 2004;55:19-26.
31. Davidoff R. Migraine: Manifestations, pathogenesis and management, 2nd ed. New York: Oxford University Press; 2002.
32. Pryse-Phillips W, Dodick D, Meads E, et al. Guidelines for the diagnosis and management of migraine in clinical practice. Can Med Assoc J 1997;156:1273-1287.
33. Monastero R, Camarda C, Pipia C, et al. Prognosis of migraine headaches in adolescents. Neurology 2006;67: 1353-1356.
34. Malick A, Burstein R. Peripheral and central sensitization during migraine. Functional Neurology 2003;15(supp)28-35.
35. Graves B. Management of migraine headaches. J Midwifery Womens Health 2006;51:174-184.
36. Carleton S, Shesser R, Pietrzak M, et al. Double-blind multicenter trial to compare the efficacy of intramuscular dihydroergotamine plus hydroxyzine versus intramuscular merperidine plus hydroxyzine for the emergency department treatment of acute migraine headache. Ann Emerg Med 1998;32:129-138.
37. Jones J, Sklar D, Dougherty J, et al. Randomized double blind trial of intravenous prochlorperazine for the treatment of acute headache. JAMA 1989;261:1174-1176.
38. Schreiber CP. The pathophysiology of primary headache. Prim Care Clin Office Pract 2004;31:261-276.
39. Jones J, Pack S, Chun E. Intramuscular prochlorperazine vs. metoclopramide as single agent therapy for the treatment of acute migraine headache. Ann Emerg Med 1996 14:262-264.
40. Coleman I, Brown M, Innes G, et al. Parenteral metoclopramide for acute migraine: A meta analysis of randomized controlled trials. BMJ 2004 doi:10.1136/bmj.38281.595718.7c.
41. American Academy of Family Physicians. Migraine headaches: How to deal with the pain. Available at www.aafp.org/atp.
42. Blumenthal HJ, Rapoport AM. Common headache syndromes. In: Warfield CA, Bajwa ZH, eds. Principles and Practice of Pain Management, 2nd ed. McGraw-Hill; New York:2004:209-215.
43. Young WB, Gangal KS, Aponte RJ, et al. Migraine with unilateral motor symptoms: A case control study. J Neurol Neurosurg Psychiatry 2007;78:600-604.
44. Saper J. Headache disorders. Med Clin NA 1999:83:663-690.
45. Bigal M, Lipton R, Krymchantowski A. The medical management of migraine. AMJ Therapeutics 2004;11:130-140.
46. Detsky M, McDonald D, Baerlocher M, et al. Does this patient with headache need neuroimaging? JAMA 2006;296: 1274-1283.
47. Gunner K, Smith H. Practice guideline for diagnosis and management of migraine headaches in children and adolescents: Part one. J Ped Health Care 2007;21:327-332.
48. Brandes JL, Kudrow D, Stark SR, et al. Sumatriptan-naproxen for acute treatment of migraine: A randomized trial. JAMA 2007;297:1443-1454.
49. Limroth V, Katsarava Z. Medication overuse headache. Curr Opin Neurology 2004;17:301-306.
50. Maizels M. Headache evaluation and treatment by primary care physicians in an emergency department in the era of triptans. Arch Int Med 2001;161:1969-1973.
51. Silberstein S, Rosenberg J. Multispecialty consenses on diagnosis and treatment of headache. Neurology 2000;54: 1553-1555.
52. Mellick LB, McIlrath ST, Mellick GA. Treatment of headaches in the ED with lower cervical intramuscular bupivacaine injections: A 1-year retrospective review of 147 patients. Headache 2006;46:1441-1449.
53. Wang SJ, Silberstein SD, Young WB. Droperidol treatment of status migrainosus and refractory migraine. Headache 1997;37:377-382.
54. Richman PB, Reischel U, Ostrow A, et al. Droperidol for acute migraine headache. Am J Emerg Med 1999;17: 398-400.
55. Richman PB, Allegra J, Eskin B, et al. A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache. Am J Emerg Med 2002;20:39-42.
56. Silberstein SD, Young WB, Mendizabal JE, et al. Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial. Neurology 2003;60:315-321.
57. Friedman BW, Corbo J, Lipton RB, et al. A trial of metoclopramide vs. sumatriptan for the emergency department treatment of migraines Neurology 2005;64:463-468.
58. Balnda M, Ranch T, Gerson L, et al. Intranasal lidocaine for the treatment of migraine headache: A randomized controlled trial. Acad Emerg Med 2001;8:337-342.
59. Matchair D, Young W, Rosenberg J. Evidence-based guidelines for migraine headache in the primary care setting: Pharmacological management of acute attacks. U.S. headache consortium.
60. May A, Goodbsy P. The trigeminovascular system in humans: Pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J Cereb Blood Flow Met 1999;19:115-127.
61. Lainez M, Dominguez M, Rejas S, et al. Development and validation of the migraine screen questionnaire. Headache 2005;45:1328-1338.
62. Cady RK, Sheftell F, Lipton RB, et al. Effect of early intervention with sumatriptan on migraine pain: Retrospective analyses of data from three clinical trials. Clin Ther 2000; 22:1035-1048.
63. Carelton S, Sbesser R, Pietrzak M, et al. Double bland multicenter trial to compare the efficacy of intramuscular dihydroergotamine plus hydroxyzine versus intramuscular merperidine plus hydroxizine for the emergency department treatment of acute migraine headache. Ann Emerg Med 1998;32:129-138.
64. Colman I, Brown M, Innes G, et al. Parenteral dihydroergotamine for acute migraine headache: A systematic review of the literature Ann Emerg Med 2005;45:393-401.
65. Mathew N, Kailasam J, Meadors L, et al. Intravenous valproate sodium (depacon) aborts migraine rapidly: A preliminary report. Headache 2000;40:720-723.
66. Mosser S, Guyuron B, Jamis J, et al. The anatomy of the greater occipital nerve: Implications for the etiology of migraine headaches. Plas Recon Surg 2004;113:693-697.
67. Mathew N. Transformed migraine, analgesic rebound and other chronic daily headaches. Neuro Clinics 1997:15: 167-186.
68. Tepper SJ. Debate: Analgesic overuse is a cause, not consequence, of chronic daily headache. Headache 2002;42: 543-547.
69. Bahra A, Walsh M, Menon S, et al. Does chronic daily headache arise de novo in association with regular use of analgesics? Headache 2003;43:179-190.
70. Ramirez-Lassepas M, Espinosa C, Cicero S, et al. Predictors of intracranial pathology findings in patients who seek emergency care because of headaches. Arch Neuro 1997;54: 1506-1509.
71. Lipton R, Dodick D, Sadousky R, et al. A self-administered screen for migraine in primary care. Neurology 2003;61: 375-382.
Patients experience headache more than any other form of pain. Headaches account for more than 10 million physician visits annually, including 0.5-2.7% of emergency department (ED) visits.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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