Treatment of migraine in the emergency department

DRUG DEVELOPMENT RESEARCH 68:360–368 (2007)

Clinical Commentary

Treatment of Migraine in the Emergency DepartmentGary Hunter and Jose F. Tellez-Zenteno�

Division of Neurology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Strategy, Management and Health Policy

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ABSTRACT Migraine is defined as a severe, episodic, unilateral, throbbing headache accompanied bynausea, photophobia, visual symptoms, and neurological manifestations. The goal of acute migrainetreatment is to ensure a prompt cessation of pain and associated symptoms and resumption of normalactivity. Additional considerations include minimizing adverse effects and cost of therapy. As for allneurological patients, a careful history is the first and most critical step in diagnosis and management. Formany years, NSAIDs and dihydroergotamine were the main medications used to treat migraine in theemergency setting. In 1993, sumatriptan was introduced as an effective medication to treat migraine. Sincethen a generation of medications mechanistically similar to sumatriptan have been introduced that shownotable benefits in the treatment of migraine. Over the years, other treatments have been introducedincluding dexamethasone, magnesium, and metoclopramide. In this article, we review the best evidenceregarding the acute treatment of migraine, describing major advances and the conventional drugs thatremain as effective treatments. Drug Dev Res 68:360–368, 2007. �c 2007 Wiley-Liss, Inc.

Key words: migraine treatment; triptans; acute treatment; dihydroergotamine

INTRODUCTION

The spectrum of symptoms resulting frommigraine pathology is vast, but typically consistsof moderate to severe throbbing pain, often lateralizing,and associated with nausea, vomiting, and sensitivity tolight and sound [Silberstein et al., 1991a]. Aura occurs inone-third of patients, and most commonly manifests asvisual symptoms of scintillating scotoma. The severity ofpain and associated symptoms varies widely, from minorheadache or aura without pain, to the acute disablingfeatures encountered in the emergency room setting[Tellez-Zenteno et al., 2005]. This latter presentation ofmigraine will be the focus of this overview.

As in any neurological consultation, the first stepis a careful history and physical examination as well asappropriate tests to ensure accurate diagnosis [Silber-stein et al., 1991b]. From there, an individualizedapproach that ascertains degree of disability, medicalcomorbidities, and usual course of the attacks ismandatory.

The selection of individual agents or combina-tions therefore is then tailored to provide the mosteffective therapy, with options including a numberof nonspecific analgesics, as well as a growing numberof migraine-specific medications. Finally, an approachto refractory acute migraine and a brief review ofnewer treatments will be undertaken.

Historical Treatments

Descriptions of migraine headache and itstherapies can be dated back at least to the time ofHippocrates in 400 BC, when he described visualauras, typical headaches, and vomiting as a cluster of

DDR

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/ddr.20202

�Correspondence to: Jose Francisco Tellez-Zenteno, Divi-sion of Neurology, Department of Medicine, Royal UniversityHospital, 103 Hospital Drive, Box 26, Room 1622, Saskatoon SKS7N OW8, Canada. E-mail: [email protected]

�c 2007 Wiley-Liss, Inc.

symptoms in certain patients [Silberstein et al., 1991c].For the next 1,500 years, treatment of migraine wasbased largely on resolution of ‘‘humoral’’ balance and‘‘liver pills.’’

Until quite recently, Wolff’s [Wolff, 1963] theoryof vasoreactive pathology as the underlying cause ofmigraine symptomatology was widely accepted.Thus, migraine treatments were largely targeted atmodulating the two described phases of the disorder,namely the aura, which was thought secondary tovasoconstriction, and the headache, a presumedconsequence of vasodilatation. This eventually led tothe application of a wide array of vasoconstrictiveagents, including ergots, caffeine, isometheptene,serotonin, and triptans. Ergotamine was present inextracts of ergot and was used to treat migraine since1862 by physicians such as Edward Woakes in Englandand Albert Eulenburg in Germany [Eulenburg, 1883;Woakes, 1868]. In 1918, Stoll isolated ergotamine fromvarious alkaloids present in extracts of the sclerotiaof the fungus Claviceps purpurea [Stoll, 1918],which grow on rye and, to a lesser extent, on othergrasses. Between 1925 and 1928, ergotamine wasbeginning to be used again to treat migraine attacks[Maier, 1926; Tzanck, 1928] with good results afterthe initial use by Woakes and Eulenburg [Eulenburg,1883; Woakes, 1868]. The first controlled ergotaminestudy was conducted in the Unites States by Lennox[1934] showing good results and since this time hasbeen used to treat migraine. Ergots, while effectiveat abating migraine, have been limited by contra-indicated use in vascular disease, severe nausea, andrebound phenomena.

While Wolff’s theory of primary vasoreactivepathology has now fallen out of favor, his recognitionthat the brain was insensate, and therefore that painmust originate in the vasculature or meninges [Wolfand Trimble, 1985], was invaluable in leading toeffective treatments.

Another pivotal event leading to advances inmigraine treatment was that of Anthony et al. [1967,1968], who found that reserpine, a vasodilator, couldinduce migraine, and that 5HT levels were decreasedin migraineurs but not controls when subjected to themedication. Trials of 5HT were successful in producingvasoconstriction, and in relieving migraine, but at theexpense of intolerable side effects including bloodpressure fluctuations, diaphoresis, and intractablenausea [Kimball et al., 1960; Kimball and Friedman,1961].

Ultimately, effective treatments for acutemigraine were extremely limited until the arrivalof triptans in the late 1980 s. Humphrey [2007] testedagonists of multiple 5HT receptors and eventually

found that, of the agents tested, only sumatriptan hadsignificant vasoactive properties without the unfavour-able side effects of ergots and serotonin. Sumatriptanwas approved for use in 1993 [Cady et al., 1991;TSSIGS, 1991], and since then a myriad of similarmedications with various routes of administration havebecome available, and have revolutionized the treat-ment of this disabling condition, much to the delight ofpatients and their treating physicians.

Goals of Treatment

The goals of migraine treatment are obvious andneed minimal emphasis: prompt cessation of painand associated symptoms and resumption of normalactivity should be the goals of patient and physician[Arulmozhi et al., 2005]. Additional considerationsshould include minimizing adverse effects and the costof therapy. When applicable, therapies that mayaddress more than one problem for the patient deservepriority.

Approach to the Acute Migraine Patient

As for all neurological patients, a careful historyis the first and most critical step in diagnosis andmanagement [Silberstein et al., 1991a]. While notall migraineurs will meet strict criteria for migraine asoutlined in the International Classification of HeadacheDisorders, most will [International Headache Society,1988], headache with features suggestive of migraine inthe setting of personal or family history of migraineis very likely to be of migraine etiology, even withoutmeeting these criteria. However, the core featuresof severe, unilateral, pulsating headache aggravatedby activity, combined with nausea and/or vomitingor stimulus sensitivity (light/sound) remain of utmostimportance while eliciting the history [Silberstein et al.,1991a]. The presence of classic auras can be extremelyhelpful if they match traditional descriptions or aresimilar to previous auras, or can complicate the case ifthe aura is not usual for the patient or has prominentnegative features such as visual loss, aphasia, orweakness, in which case a more extensive workup isnecessary [Silberstein et al., 1991d].

The history must also inquire directly about thenature and frequency of previous attacks, previoustherapies and their successes and failures, specificlimitations for the patient such as allergies and sideeffect profiles, and personal preferences. Social aspectsmust be included in the headache history, includingtobacco, alcohol, and drug use, as well as impact onsocial function and access to funding for prescriptions[Silberstein et al., 1991a,d].

Given the wide spectrum of potential deficitsassociated with migraine and the broad differential

361ACUTE TREATMENT OF MIGRAINE

Drug Dev. Res. DOI 10.1002/ddr

diagnosis, a careful physical exam is mandatory inruling out more sinister causes of headache, especiallywhen prominent systemic symptoms are present.Special attention should be paid to assessment offundi, visual fields, eye movements, and the motorexamination [Silberstein et al., 1991a,d].

Nonspecific Treatments

Once the diagnosis has been established,non-pharmacological measures should be taken tomaximize patient comfort. This includes reassurancethat the diagnosis is, in fact, migraine, and not a moremalicious disorder such as stroke or brain tumor.Second, the patient should be placed in a dark roomwith minimal environmental stimulation if possible,recognizing that this is often difficult or impossible inthe Emergency Room. Finally, ensure the patient isadequately hydrated, providing intravenous fluid asnecessary, especially if nausea and vomiting have beenprolonged.

Nonspecific Drugs for Acute Migraine

The fact that migraine has been a difficult illnessto treat is evidenced by the extensive list of medicationsshowing some evidence for efficacy. The list includesNSAIDs such as ASA, acetaminophen, and naproxen,which are used alone or in combination with caffeineand ergotamine. Other drugs have also been usedsuch as neuroleptics, anticonvulsants, antihistamines,barbiturates, and opioids.

Given that none of these has emerged as clearlysuperior to the others, one can only sensibly concludethat none is highly effective for the treatment of acutemigraine. Nonetheless, many have proven superiorto placebo, and NSAIDs may be appropriate choicesin patients without severe migraine and intoleranceor lack of access to triptans. In the practice parameterpublished in 2000 by the American Academy ofNeurology (AAN), evidence for the acute treatmentof migraine was rated from I to IV, Group I being thestronger evidence. Acetaminophen or aspirin pluscaffeine, aspirin, ibuprofen, and naproxen sodium wereincluded in the Group I (proven, pronounced statisticaland clinical significance). Included in Group II(moderate statistical and clinical benefit) wereacetaminophen plus codeine, diclofenac, ketorolac,and naproxen. Acetaminophen was included in GroupIV (clinical and statistical significance unknown)[Silberstein, 2000].

A recent European task force rated the informa-tion in level A, B, and C, A being the strongestrecommendation (best evidence) [Evers et al., 2006].This study showed similar results to the consensusperformed in 2000 by the AAN, and aspirin, ibuprofen,

naproxen, diclofenac, and aspirin or paracetamol pluscaffeine were rated with a level A of recommendation.A recent randomized clinical trial showed that thecombination of sumatriptan (85 mg) plus naproxen(500 mg) had a better efficacy compared with suma-triptan alone, opening the door for future trialscombining triptans with the medications that havebeen used over the years such as the NSAIDs [Brandeset al., 2007]. In general, NSAIDs are a proven optionfor acute treatment and their use should be imple-mented when appropriate.

A popular treatment for acute migraine over thelast several years has been the neuroleptic metoclo-pramide, which is a D2 dopamine receptor antagonistwith gastric motility and anti-nausea effects. As withother antidopaminergics, metoclopramide has thepotential to cause dystonic reactions and is used withcaution, especially in elderly patients. However, it isgenerally well tolerated and a meta-analysis of rando-mized controlled trials has demonstrated its efficacy inacute migraine therapy [Colman et al., 2004a]. Fried-man et al. [2005] compared metoclopramide versussubcutaneous sumatriptan in the treatment of acutemigraine, concluding that metoclopramide has similarefficacy to sumatriptan. The study was criticizedto some extent for combining diphenhydramine withmetoclopramide, since diphenhydramine may havesome benefit in treating migraine independently[Friedman et al., 2005]. The intent of diphenhydra-mine administration in this study was for prophylaxisagainst dystonic reactions while using high-doseneuroleptics. It should also be noted that this authorused 20 mg of metoclopramide given up to four timesin 2 h. Fifty-nine percent of patients in the metoclo-pramide arm were pain free at 2 h, versus 35% ofpatients in the sumatriptan group. The primaryoutcome of change in the pain scale rating at 2 h didnot achieve statistical significance. One can concludefrom this evidence that metoclopramide combined withdiphenhydramine may be an effective regimen for theacute treatment of migraine, especially for patientswith contraindications to vasoactive medications suchas triptans, including those with vascular disease. In therecent task force from Europe [Evers et al., 2006],metoclopramide was considered as level B of evidencein agreement with the practice parameter of the AANwhere metoclopramide IV was included in Group II (Ito IV) and metoclopramide IM in group 3 (provenstatistically but not clinically) [Silberstein, 2000].According to the available evidence, metoclopramidecould be especially useful in patients with prominentnausea.

There is also some evidence to suggest thatintravenous magnesium may be a viable option for

362 HUNTER AND TELLEZ-ZENTENO


acute migraine treatment. Its use in this setting stemsfrom findings in animals suggesting a link betweenhypomagnesemia and cortical spreading depression[Mody et al., 1987]. Magnesium is also known to affectvascular tone and nitric oxide production [Altura andAltura, 1978] and substance P [Weglicki and Phillips,1992]. Bigal et al. [2002] compared magnesiumsulphate 1 g IV with placebo in the acute treatmentof migraine, and found that 36.7% of patients with aurain the treatment group were pain free at 2 h, comparedto 6.7% of placebo patients. The difference was notas robust for those without aura. Magnesiumwas effective for relief on nausea regardless of aurastatus in this study. Cete et al. [2005] compared IVmagnesium with IV metoclopramide or placebo in ablinded controlled study of 113 patients and found thatmagnesium had significantly reduced pain scores at15 min, but there was no difference at 30 min. Whilethe placebo and metoclopramide groups required morerescue medications than the magnesium group, theauthors concluded that metoclopramide and magne-sium were not more effective than placebo in thisgroup of patients with acute migraine. However, theyrecognized that the number of patients with aura intheir study was relatively small. Other randomizedclinical trials compared magnesium plus metoclopra-mide vs. metoclopramide [Corbo et al., 2001]. Surpris-ingly, there was no benefit to adding magnesium tometoclopramide. Finally, in a randomized singleblinded trial comparing 1 g of magnesium versusplacebo [Demirkaya et al., 2001], magnesium wasfound to be safe and efficient in treating acute migraineattacks. Further studies using magnesium in acutemigraine are needed, especially with respect todifferences based on the presence of aura, but givenits safety and available evidence, it remains a reason-able option for some patients.

Finally evidence of opioid use in the acutetreatment of migraine is very poor and is notconsidered an alternative for management. In the taskforce generated in Europe, opioids were not recom-mended, and in the practice parameter from the AANpublished in 2000, methadone IM was the onlyopiod that was recommended for acute treatmentand was graded as level II (moderate statistical andclinical benefit) of evidence. Despite lack of goodevidence for narcotics as first line therapy, recentstudies demonstrate that these medications are stillbeing frequently employed in this manner [Colmanet al., 2004b], perhaps as a ‘‘knee-jerk’’ response topatients with severe pain. Given the lack of evidence,less favourable side effect profiles, and potential forabuse, narcotics should be avoided in the treatment ofacute migraine.

Migraine Specific Treatments

DihydroergotamineDihydroergotamine (DHE) has been used

routinely to treat migraine since the randomized trialof Lennox [1934]. The Practice parameter forevidence-based treatment for migraine that was devel-oped in 2000 by the Quality Standards Subcommitteeof the AAN recommended dihydroergotamine mesy-late for use in the acute treatment of moderateor severe migraine, as well as for mild to moderateheadaches that have not responded to NSAIDs orcombination products (such as aspirin plus acetamino-phen plus caffeine) [Silberstein and Young, 1995]. Inthese guidelines, each medication was graded accord-ing to the strength of the evidence from A (bestevidence, mainly based on randomized clinical trials),B (some evidence from randomized clinical trials, butthe scientific support is not optimal), and C (notadequate evidence due to the lack of randomizedcontrolled trials). Intranasal DHE was rated as grade Aevidence, while intramuscular and subcutaneous for-mulations have a rating of grade B. In addition to thisrating scheme, the evidence for acute treatment wasscored in the AAN Grouping. All four delivery routesfor DHE (intravenous, intramuscular, subcutaneous,and intranasal) were designated as Group I. A specificpractice parameter and numerous reviews in recentyears also support its use [American Academy ofNeurology, 1995; Saper et al., 2006]. Despite thesupportive data showing the proven clinical effective-ness of DHE in the acute treatment of migraine, its usehas waned in clinical practice compared to other drugswith similar safety and supportive efficacy data. Thismay be due in part to its poor bioavailability andtendency to cause severe nausea even at low doses, aswell as minimal marketing attention compared withtriptans. Contraindications are similar to triptans,mainly with respect to vascular disease. Only parenteralformulations are available precluding patients fromself-medicating on an ambulatory basis. Finally in-tranasal DHE, which has demonstrated high efficacy inthe acute treatment of migraine, has not gainedpopularity over the years. This may be a result of thefirst intranasal delivery system being cumbersome touse and minimal marketing compared with triptans,and a tendency to cause nasal congestion. Some recentrandomized clinical trials and metanalyses suggest thattriptans can be better than DHE, although morestudies are needed in the future [McCrory and Gray,2003; Lainez, 2003]. In general, the use of DHE hasrobust evidence since 1936 and its use is advised in anemergency setting where the intravenous formulationsare available and there are no contraindications.



Triptan Mechanisms

It is now well accepted that migraine symptomsarise from activation of trigeminovascular systems andthe release of vasoactive neuropeptides in geneticallysusceptible individuals [May and Goadsby, 1999; Goads-by and Edvinsson, 1993]. The role of 5HT in themigraine cascade is supported by findingsthat 5HT1B receptors are heavily concentrated inmeningeal vessels and can modulate smooth musclevasoconstriction [Bussone, 2004; Welch, 2003a,b].5HT1D receptors are found in both peripheral andcentral trigeminal projections, where they inhibit neuro-peptide release and central pain transmission, respec-tively [Hargreaves, 2007]. While the vasoconstrictiveproperties of triptans are approximately 10 times morepotent in the meningeal vasculature compared tocoronary vessels, 5HT1B receptors are found in cardiacvessels, and triptans are therefore contraindicated inpatients with known cardiovascular and cerebrovasculardisease [Hargreaves, 2007; Welch, 2003a].

Selecting a triptanThere are at least seven triptans available, each

with slightly different profiles with respect to speed,administration, cost, and availability. Several rando-mized clinical trials have been published about theiruse in migraine and probably the best evidenceconsidering the large amount of articles are systematicreviews and metanalyses. The first systematic reviewwas published in 2000 and compared the rate of headrelief and the mean therapeutics gain defined aspercentage relief with active drug minus percentagerelief with placebo [Tfelt-Hansen et al., 2000]. Themean therapeutic gain with sumatriptan s.c. 6 mg was51%, sumatriptan p.o. 100 mg 32%, sumatriptan 50 mgp.o. 29%, intranasal sumatriptan 20 mg 30%, rectalsumatriptan 25 mg 31%, zolmitriptan 2.5 mg p.o. 32%,rizatriptan 10 mg p.o. 37%, eletriptan 40 mg p.o. 37%,and almotriptan 12.5 mg p.o. 26%. In this study,the authors concluded that comparative randomizedclinical trials with oral triptans revealed similar results.The recurrence of headache within 24 h after an initialsuccessful response occurred in 30–40% of sumatrip-tan-treated patients. Apart from naratriptan, which hasa tendency towards less recurrence, there appeared tobe no consistent difference in recurrence ratesbetween the newer triptans and sumatriptan. Riza-triptan with its shorter time to maximum concentration(tmax) tended to produce a quicker onset of headacherelief than sumatriptan and zolmitriptan.

A second systematic review was based on thenumber needed to treat (NNT) [Oldman et al., 2002].Forty-eight publications reporting on 54 trials were

included in the meta-analyses, with 79 placebo compar-isons for the primary outcome of headache relief at 2 h.The NNT for subcutaneous sumatriptan 6 mg was 2.0(95% CI 1.8–2.2); sumatriptan 100 mg (NNT 5 3.3, 95%CI 3.0–3.7), aspirin plus ergotamine (NNT 5 3.2, 95%CI 2.6–4.0), intranasal dihydroergotamine (NNT 5 2.5,95% CI 1.9–3.7), rizatriptan 10 mg (NNT 5 2.7, 95% CI2.4–2.9), naratriptan 2.5 mg (NNT 5 5.4, 95% CI5.4–9.2). For the pain-free outcome after 2 h, aspirinplus metoclopramide (NNT 5 8.6, 95% CI 6.2–14),sumatriptan 100 mg (NNT 5 4.7, 95% CI 4.1–5.5),sumatriptan 6 mg s.c. (NNT 5 2.1, 95% CI 1.9–2.4),and rizatriptan (NNT 5 3.1, 95% CI 2.9–3.5). Inagreement with the metanalysis of Tfelt-Hansen et al.[2000], sumatriptan s.c. showed the greatest benefit forthe acute treatment of migraine but in general all thetriptans showed similar benefits.

A third metanalysis performed in Canada in 2001,including the available triptans at that time in Canada(sumatriptan, rizatriptan, zolmitriptan, and naratriptan)also calculated the NNT [Gawel et al., 2001] and showedsimilar results to the first two metanalysis. Finally,Ferrari et al. published a metanalysis that included 53clinical trials (12 unpublished) involving 24,089 patients[Ferrari et al., 2001]. Mean headache relief results for100 mg sumatriptan were 59% (95% CI 5 57–60) for 2-hheadache response (improvement from moderate orsevere to mild or no pain); 29% (27–30) for 2-h pain free(improvement to no pain); 20% (18–21) for sustainedpain free (pain free by 2 h and no headache recurrenceor use of rescue medication 2–24 h post dose); and 67%(63–70) for consistency (response in at least two of threetreated attacks); placebo-subtracted proportions forpatients with at least one adverse event (AE) were13% (8–18), for at least one CNS AE 6% (3–9), and forat least one chest AE 1.9% (1.0–2.7). Compared withthese data, 10 mg rizatriptan showed better efficacy andconsistency, and similar tolerability; 80 mg eletriptanshowed better efficacy, similar consistency, but lowertolerability; 12.5 mg almotriptan showed similar efficacyat 2 h but other better results; 2.5 mg naratriptan and20 mg eletriptan showed lower efficacy and (the first two)better tolerability; 2.5 mg and 5 mg zolmitriptan, 40 mgeletriptan, and 5 mg rizatriptan showed very similarresults. The results of the 22 trials that directly comparedtriptans showed the same overall pattern. In general, thismetanalysis concluded that all oral triptans were welltolerated and effective. Rizatriptan (10 mg), eletriptan(80 mg), and almotriptan (12.5 mg) provided betterbenefits.

With the information generated over the years,some points emerged: firstly all the triptans are safe totreat migraine, have a better efficacy compared withplacebo, differences of clinical effectiveness between



the different triptans are mild, some triptans haveequivalent and some them higher efficacy than classicmedications such as DHE with fewer side effects andbetter efficacy than NSAIDs. Given that there is noclear difference in overall efficacy among currentlyavailable triptans, only a few decision points apply. Onetruism that has emerged is that triptans are mosteffective if given early in the course of symptoms,particularly if given prior to development of cutaneousallodynia [Rozen, 2007; Goadsby, 2006; Linde, 2006;Ramadan and Buchanan, 2006]. Early treatmentprobably also decreases the recurrence rate if givenwithin the first 90 min [Diamond et al., 2006; Rapoportet al., 2006a; Rozen, 2006]. Patients who are naıve totriptans should be advised of typical side effects,including paresthesias, warm sensations, dizziness,and flushing, all of which are generally short-livedand well tolerated if they occur [Tfelt-Hansen, 2006].Rare side effects include a wide array of nonspecificcomplaints of motor dysfunction, cognitive slowing, orchest discomfort.

The first step is to decide which route ofadministration will be most effective for the currentpatient [Rapoport et al., 2006b]. If vomiting is a majorconcern, as it may well be in the acute setting, nasalspray, subcutaneous, or suppository administrationmay be most effective [Rapoport et al., 2006b]. If thepatient is encountered early in the course of migraine,oral medications are the easiest to administer andprovide adequate relief in most cases [Rapoport et al.,2006b]. An even more basic but equally importantquestion is whether the patient has used triptans beforeand which formulations have been effective, since atpresent there are no accurate predictors of whichpatients will respond to which triptans [Rapoport et al.,2006b]. In Table 1 are summarized the availabletriptans, recommended doses, and the most frequentside effects.

Status Migrainosus

Migraine episodes that persist for at least 3 daysdespite treatment are termed status migrainosus.

TABLE 1. Pharmacologic Options for Treatment of Acute Migraine

Non-specific Dose Adverse effects Comments

Ibuprofen 800 mg po Gastrointestinal irritationAcetaminophen 1000 mg po Minimal Caution with hepatic disease,

EtOHNaproxen 500 mg po Gastrointestinal irritation Caution with peptic ulcer

disease, renal failureKetorolac 30 mg IV, 60 mg IM Gastrointestinal pain, dyspepsia,

nauseaNon sedating

Metoclopramide 10 mg IV, may be repeatedafter 1–2 hrs

Acute dystonic reactions, mildsedation

Caution in elderly, Parkinson’sdisease, history of movementdisorder

Ondansetron 4–8 mg IV Diarrhea, constipation, headacheProchlorperazine 10 mg IV Acute dystonic reactions, mild

sedation

SpecificSumatriptan 1. 50 mg po, may be repeated

in 1 h 2. 5–20 mg nasal spray3. 6 mg SC 4. 25 mg pr

All triptans may cause flushing,paresthesias, drowsiness

All triptans contraindicatedwith vascular disease

Eletriptan 20–40 mg poNaratriptan 1–2.5 mg poRizatriptan 5–10 mg po or disintegrating tabletZolmitriptan 2.5 mg po or 5 mg nasal sprayAlmotriptan 12.5–25 mgFrovatriptan 12.5–25 mgDHE 1 mg SC, IM, IV Nausea Contraindicated in vascular

disease

RescueDexamethasone 4–10 mg IV GI irritation, insomniaValproic acid 500–1000 mg IV Minimal Caution with hepatic

impairment, EtOHMagnesium 1–2 g IV Minimal Most effective for migraine with

aura



Traditionally, these long-lasting migraine episodes weretreated with brief in-patient hospitalizations withIV medication [Marcus, 2001]. Practically speaking,when to make this designation is subject to individualexperience and local practices, but the diagnosis servestwo important purposes. First, the clinician shouldquestion the diagnosis and consider again moremalicious causes of headache. For example, if subar-achnoid hemorrhage has not been adequately ruledout, and the migraine is atypical or new suggestivefeatures emerge from the history, a lumbar puncture ismandatory. Second, the diagnosis of status migrainosusalerts the treating physician that other routes oftherapy may need to be offered. These ‘‘rescue’’therapies include little in the way of evidence-basedtreatments, but conventional wisdom has seen thempersist nonetheless. These options include shortcourses of corticosteroids such as intravenous dexa-methasone, or other options such as magnesium,valproate, and dihydroergotamine [Hawken et al.,2001; Stead and Josephs, 2005; Alberca et al., 1995;Raskin, 1990]. These should probably be reserved forselect patients without contraindications who have notresponded to adequate trials of triptans and NSAIDs,and trials of their use in this setting would be helpful inelucidating their exact role in the treatment of acutemigraine.

Emerging Treatments

Interest in calcitonin gene-related peptide(CGRP) antagonists has seen a resurgence recently,largely based on research demonstrating its releaseduring stimulation of trigeminal ganglia and corre-sponding vascular effects, increased levels of CGRP inmigraineurs, and correlations between CGRP levelsand migraine intensity [Goadsby, 2007; Hargreaves,2007; Buldyrev et al., 2006]. The relationship betweenmigraine and epilepsy has long been questioned andstudied, and now seems well established, especiallygiven some new findings in the field of genetics[Deprez et al., 2007]. While the main impetus forstudying anticonvulsant drugs to this point has beenmigraine prophylaxis, acute treatment with valproatehas been advocated as rescue therapy for somepatients, especially those with comorbid epilepsy orfamilial hemiplegic migraine [Spina and Perugi, 2004].Other newer agents such as lamotrigine and topiramateare currently used as prophylactic agents and may alsobecome options in the acute setting with more research[D’Amico, 2007]. More recently, leviteracetam hasemerged as a possible option for acute migraine withcomorbid epilepsy [Farooq et al., 2007], although mostevidence to date has been in the form of animal studiesor case reports.

CONCLUSIONS

Prompt cessation of pain and associated symp-toms and resumption of normal activity should be thegoals of patient and physician

As for all neurologic patients, a careful history isthe first and most critical step in diagnosis andmanagement

NSAIDs are frequently used for the acutetreatment of migraine and the evidence is adequatefor some medications such as aspirin, ibuprofen,naproxen, diclofenac, and aspirin or paracetamol pluscaffeine

The use of dihydroergotamine has strongevidence since its introduction in 1925. Its use hasdeclined over the years due to lack of marketing but itsefficacy is not questioned

Since the introduction of sumatriptan in 1993, ageneration of medications similar to sumatriptan havebeen introduced. Currently, these are considered thebest medications in the treatment of migraine with avery well-demonstrated clinical efficacy

Metoclopramide is a medication that has beenused over the years for migraine and probably the mainuse is in patients with prominent nausea

Magnesium is a safe therapy and some initialtrials have shown good efficacy in the treatment ofpatients with migraine.

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Treatment of migraine in the emergency department