Managing Migraine

Abstract

Migraine is a recurrent headache disorder that afflicts 18% of US women and 9% of US men.1Victor T.W. Hu X. Campbell J.C. et al.Migraine prevalence by age and sex in the United States: a life-span study.Cephalalgia. 2010; 30: 1065-1072Crossref PubMed Scopus (295) Google Scholar It causes at least 1.2 million visits to US emergency department (EDs) annually; the actual number is probably substantially larger because many migraine patients are assigned nonspecific headache diagnostic codes.2Friedman B.W. West J. Vinson D.R. et al.Current management of migraine in US emergency departments: an analysis of the National Hospital Ambulatory Medical Care Survey.Cephalalgia. 2015; 35: 301-309Crossref PubMed Scopus (62) Google Scholar Migraine severity, as measured by the frequency with which it disrupts a patient’s life, ranges from minimal to severe. On one end of this spectrum are patients who have occasional headaches that are rapidly and effectively treated with over-the-counter therapies. On the other end are patients with chronic migraine. They have headache on more days than not and their work and social life is detrimentally affected. An aura is one of several reversible neurologic phenomena that precede the headache and resolve completely. Most commonly, these are visual or sensory, although they may involve motor function or speech. Migraine patients also frequently report neurologic phenomena including dizziness, sensory disturbances, and visual symptoms during the acute attack. Because they occur during the headache, these latter symptoms are not typically referred to as aura. The migraine prodrome is a constellation of symptoms that precede the acute migraine attack by several days and include changes in mood, alertness, and appetite. Allodynia, an alteration of nociception that causes typically non-noxious sensory stimuli (such as brushing one’s hair or shaving one’s face) to be perceived as painful, develops as acute migraine duration increases. This is thought to indicate involvement of higher-order central nervous system sensory relay stations, notably, the thalamus. Migraine was once believed to be a vascular headache. Advanced imaging studies do not support this description and indicate that migraine is a neurologic disorder involving dysfunctional nociceptive processing.3Goadsby P.J. Pathophysiology of migraine.Ann Indian Acad Neurol. 2012; 15: S15-22Crossref PubMed Scopus (91) Google Scholar Abnormally activated sensory pathways turn non-noxious stimuli into headache, photophobia, phonophobia, and osmophobia. Cortical spreading depression, a slow wave of brain depolarization, underlies migraine aura but has not been demonstrated clearly in migraine patients without aura. Migraine is a clinical diagnosis. There are currently no laboratory or imaging findings available to confirm this diagnosis. The International Headache Society’s International Classification of Headache Disorders, currently in its third iteration, is used to standardize the diagnosis for both research studies and clinical practice.4Olesen J. Bendtsen L. Dodick D. et al.The International Classification of Headache Disorders, 3rd edition (beta version).Cephalalgia. 2013; 33: 629-808Crossref PubMed Scopus (41) Google Scholar The specific criteria for migraine are somewhat cumbersome (Figure 1) and may be difficult to ascertain during a severe acute attack. ID-Migraine (Figure 2), a 3-item screening instrument that has been validated against expert diagnosis in the outpatient setting, seems apropos to ED patients with recurrent headaches.5Lipton R.B. Dodick D. Sadovsky R. et al.A self-administered screener for migraine in primary care: the ID Migraine(TM) validation study.Neurology. 2003; 61: 375-382Crossref PubMed Scopus (417) Google ScholarFigure 2ID-Migraine.5Lipton R.B. Dodick D. Sadovsky R. et al.A self-administered screener for migraine in primary care: the ID Migraine(TM) validation study.Neurology. 2003; 61: 375-382Crossref PubMed Scopus (417) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT) Some question the need to establish a specific primary headache diagnosis among ED patients. Central to this argument is the observation that other primary headaches (cluster and tension-type headache) respond to many of the same medications as does migraine, including triptans,6Miner J.R. Smith S.W. Moore J. et al.Sumatriptan for the treatment of undifferentiated primary headaches in the ED.Am J Emerg Med. 2007; 25: 60-64Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 7Sumatriptan Cluster Headache Study GroupTreatment of acute cluster headache with sumatriptan.N Engl J Med. 1991; 325: 322-326Crossref PubMed Scopus (387) Google Scholar antidopaminergics,8Weinman D. Nicastro O. Akala O. et al.Parenteral treatment of episodic tension-type headache: a systematic review.Headache. 2014; 54: 260-268Crossref PubMed Scopus (24) Google Scholar, 9Rozen T.D. Olanzapine as an abortive agent for cluster headache.Headache. 2001; 41: 813-816Crossref PubMed Scopus (45) Google Scholar and nonsteroidal anti-inflammatory drugs. There is truth to this argument, and it is reasonable to delay diagnosis until the end of the ED visit. However, before discharge, providing patients with a specific headache diagnosis will allow them to access resources and discuss their headache disorder knowledgably. With the exception of a pregnancy test, which may be used to guide treatment, routine laboratory tests are unlikely to contribute to clinical management and should not be ordered. Similarly, neuroimaging is not indicated for patients who present with a typical migraine exacerbation. It is unknown whether patients who present with a headache that is somewhat different from their typical migraine require neuroimaging. These latter patients may present with a migraine that did not respond as it usually does to standard medication, one that is longer or more intense than usual, or one that occurs in a different location than usual. In the author’s experience, absent typical red flags (thunderclap onset, focal neurologic findings, fever, head trauma, or altered mental status), these patients are at low risk for pathologic findings. In these latter patients, decisions on neuroimaging should be delayed until after treatment. For many patients, successful treatment provides a better perspective on the similarity of the headache to the patient’s previous headaches. This is not to say that response to treatment can exclude a malignant cause of headache. Rather, in my experience, a patient who is now headache free is better able to contextualize the acute headache in regard to previous headaches and may report that in fact the acute headache was not much different than previous headaches. Three classes of medication have emerged as first-line parenteral treatment of acute migraine: the antidopaminergics, the triptans, and nonsteroidal anti-inflammatory drugs (Table).TableFirst-line parenteral treatment of migraine.AgentDose, RouteFrequent Adverse EffectsCautions/ContraindicationsTriptansSumatriptan6 mg SCFlushing, dizziness, palpitations, drowsiness, injection site reactionsUse cautiously in patients with cardiovascular risk factors. Use cautiously in those who have already received triptans within 24 h.AntidopaminergicsMetoclopramide10 mg IVAkathisia, drowsiness, dizziness, generalized weaknessDiphenhydramine not indicated to prevent akathisiaProchlorperazine10 mg IVAkathisia, drowsinessDiphenhydramine should be used to prevent akathisiaNonsteroidal anti-inflammatory drugsKetorolac30 mg IV or 60 mg IMWell tolerated Open table in a new tab During the last 3 decades, compelling clinical evidence has emerged to support the use of antidopaminergics as monotherapy for acute migraine.10Orr S.L. Aube M. Becker W.J. et al.Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings.Cephalalgia. 2015; 35: 271-284Crossref PubMed Scopus (79) Google Scholar These medications work not just for migraine-associated nausea and gastroparesis but also to relieve the acute headache itself. This is true for various types of antidopaminergics, including metoclopramide,11Colman I. Brown M.D. Innes G.D. et al.Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials.BMJ. 2004; 329: 1369-1373Crossref PubMed Scopus (138) Google Scholar, 12Friedman B.W. Corbo J. Lipton R.B. et al.A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines.Neurology. 2005; 64: 463-468Crossref PubMed Scopus (117) Google Scholar, 13Talabi S. Masoumi B. Azizkhani R. et al.Metoclopramide versus sumatriptan for treatment of migraine headache: a randomized clinical trial.J Res Med Sci. 2013; 18: 695-698PubMed Google Scholar prochlorperazine,14Jones J. Sklar D. Dougherty J. et al.Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache.JAMA. 1989; 261: 1174-1176Crossref PubMed Scopus (167) Google Scholar, 15Kostic M.A. Gutierrez F.J. Rieg T.S. et al.A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department.Ann Emerg Med. 2010; 56: 1-6Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 16Seim M.B. March J.A. Dunn K.A. Intravenous ketorolac vs intravenous prochlorperazine for the treatment of migraine headaches.Acad Emerg Med. 1998; 5: 573-576Crossref PubMed Scopus (77) Google Scholar droperidol,17Miner J.R. Fish S.J. Smith S.W. et al.Droperidol vs. prochlorperazine for benign headaches in the emergency department.Acad Emerg Med. 2001; 8: 873-879Crossref PubMed Scopus (77) Google Scholar, 18Silberstein S.D. Young W.B. Mendizabal J.E. et al.Acute migraine treatment with droperidol: a randomized, double-blind, placebo-controlled trial.Neurology. 2003; 60: 315-321Crossref PubMed Scopus (93) Google Scholar, 19Weaver C.S. Jones J.B. Chisholm C.D. et al.Droperidol vs prochlorperazine for the treatment of acute headache.J Emerg Med. 2004; 26: 145-150Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar and haloperidol.20Gaffigan M.E. Bruner D.I. Wason C. et al.A randomized controlled trial of intravenous haloperidol vs. intravenous metoclopramide for acute migraine therapy in the emergency department.J Emerg Med. 2015; 49: 326-334Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 21Honkaniemi J. Liimatainen S. Rainesalo S. et al.Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study.Headache. 2006; 46: 781-787Crossref PubMed Scopus (65) Google Scholar Unfortunately, clinical science has outpaced basic science and a mechanism of action is not clear. Some data suggest that migraine is a dopaminergic phenomenon, but these data are neither robust nor consistent.22Charbit A.R. Akerman S. Goadsby P.J. Dopamine: what's new in migraine?.Curr Opin Neurol. 2010; 23: 275-281Crossref PubMed Scopus (82) Google Scholar Because metoclopramide has a favorable pregnancy rating, it should be considered the primary parenteral therapy for pregnant migraineurs. Although highly effective, intravenous antidopaminergics are accompanied by extrapyramidal symptoms, most commonly akathisia, a distressing syndrome of restlessness and agitation that may occur in one third of patients who receive these medications.23Vinson D.R. Drotts D.L. Diphenhydramine for the prevention of akathisia induced by prochlorperazine: a randomized, controlled trial.Ann Emerg Med. 2001; 37: 125-131Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar Akathisia is usually short-lived, but patients who experience it once report that they do not want to receive the same antidopaminergic medication again. Some use a strategy of akathisia prophylaxis by coadministering diphenhydramine, an anticholinergic. This is a strategy that is effective for prochlorperazine23Vinson D.R. Drotts D.L. Diphenhydramine for the prevention of akathisia induced by prochlorperazine: a randomized, controlled trial.Ann Emerg Med. 2001; 37: 125-131Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar but does not seem to be needed for metoclopramide.24Friedman B.W. Cabral L. Adewunmi V. et al.Diphenhydramine as adjuvant therapy for acute migraine: an emergency department–based randomized clinical trial.Ann Emerg Med. 2016; 67: 32-39Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar A slower rate of medication administration is associated with less frequent akathisia.25Vinson D.R. Migala A.F. Quesenberry Jr., C.P. Slow infusion for the prevention of akathisia induced by prochlorperazine: a randomized controlled trial.J Emerg Med. 2001; 20: 113-119Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Once it develops, akathisia should be treated with diphenhydramine or midazolam.26Parlak I. Erdur B. Parlak M. et al.Midazolam vs. diphenhydramine for the treatment of metoclopramide-induced akathisia: a randomized controlled trial.Acad Emerg Med. 2007; 14: 715-721Crossref PubMed Google Scholar Dystonic reactions are relatively uncommon. Tardive dyskinesia, an irreversible involuntary motor disorder, has never been reported after an isolated dose of an antidopaminergic.27Wijemanne S. Jankovic J. Evans R.W. Movement disorders from the use of metoclopramide and other antiemetics in the treatment of migraine.Headache. 2016; 56: 153-161Crossref PubMed Scopus (25) Google Scholar The triptans are serotonin receptor agonists that, during the last 30 years, have revolutionized the outpatient treatment of migraine.28Loder E. Triptan therapy in migraine.N Engl J Med. 2010; 363: 63-70Crossref PubMed Scopus (149) Google Scholar Although originally developed as vasoconstrictors, these medications decrease nociceptive transmission within the trigeminal pathway.28Loder E. Triptan therapy in migraine.N Engl J Med. 2010; 363: 63-70Crossref PubMed Scopus (149) Google Scholar Subcutaneous sumatriptan, the only available parenteral triptan, has an number needed to treat of 2.5 versus placebo for meaningful headache relief in the ED setting and a median time to headache relief of 34 minutes.29Akpunonu B.E. Mutgi A.B. Federman D.J. et al.Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study.Ann Emerg Med. 1995; 25: 464-469Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar In actual clinical practice, this means a migraine patient could be placed in a chair, could be administered a subcutaneous dose of medication, and likely will be ready for discharge in less than an hour. Unfortunately, sumatriptan comes with a number of unpleasant adverse effects (number needed to harm=4), including chest symptoms, flushing, and worsening of the headache.29Akpunonu B.E. Mutgi A.B. Federman D.J. et al.Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study.Ann Emerg Med. 1995; 25: 464-469Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar Also, two thirds of patients who receive sumatriptan report recurrence of headache within 24 hours.29Akpunonu B.E. Mutgi A.B. Federman D.J. et al.Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study.Ann Emerg Med. 1995; 25: 464-469Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar Sumatriptan is more likely to be effective in patients who have not developed allodynia and those who have had a favorable response to it previously. In head-to-head studies, intravenous antidopaminergics tended to be more efficacious and better tolerated than subcutaneous sumatriptan.12Friedman B.W. Corbo J. Lipton R.B. et al.A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines.Neurology. 2005; 64: 463-468Crossref PubMed Scopus (117) Google Scholar, 13Talabi S. Masoumi B. Azizkhani R. et al.Metoclopramide versus sumatriptan for treatment of migraine headache: a randomized clinical trial.J Res Med Sci. 2013; 18: 695-698PubMed Google Scholar, 15Kostic M.A. Gutierrez F.J. Rieg T.S. et al.A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department.Ann Emerg Med. 2010; 56: 1-6Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 30Esteban-Morales A. Chavez P.T. Martinez C.G.R. et al.Respuesta clinica de metoclopramida en comparacion con sumatriptan en el tratamiento de ataques agudos de migrana.Revista Sanidad Militar Mexico. 1999; 53: 36-40Google Scholar Ketorolac is the specific parenteral medication used most commonly to treat migraine in US EDs, although high-quality data supporting its use are less robust.31Taggart E. Doran S. Kokotillo A. et al.Ketorolac in the treatment of acute migraine: a systematic review.Headache. 2013; 53: 277-287Crossref PubMed Scopus (38) Google Scholar Ketorolac can be combined with either the antidopaminergics or the triptans, a strategy that is intuitively appealing, although one that has not been subjected to clinical trials. The evidence supporting other parenteral medications is less compelling. Antihistamines such as diphenhydramine and hydroxyzine probably are not efficacious in acute migraine.24Friedman B.W. Cabral L. Adewunmi V. et al.Diphenhydramine as adjuvant therapy for acute migraine: an emergency department–based randomized clinical trial.Ann Emerg Med. 2016; 67: 32-39Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Ketamine32Nicolodi M. Sicuteri F. Exploration of NMDA receptors in migraine: therapeutic and theoretic implications.Int J Clin Pharmacol Res. 1995; 15: 181-189PubMed Google Scholar and propofol33Moshtaghion H. Heiranizadeh N. Rahimdel A. et al.The efficacy of propofol vs. subcutaneous sumatriptan for treatment of acute migraine headaches in the emergency department: a double-blinded clinical trial.Pain Pract. 2015; 15: 701-705Crossref PubMed Scopus (25) Google Scholar, 34Soleimanpour H. Taheraghdam A. Ghafouri R.R. et al.Improvement of refractory migraine headache by propofol: case series.Int J Emerg Med. 2012; 5: 19Crossref PubMed Scopus (26) Google Scholar seem to work acutely, but it is unclear what happens to the headache after the medication wears off. Magnesium has not consistently shown benefit.35Bigal M.E. Bordini C.A. Tepper S.J. et al.Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study.Cephalalgia. 2002; 22: 345-353Crossref PubMed Scopus (126) Google Scholar, 36Cete Y. Dora B. Ertan C. et al.A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the emergency department.Cephalalgia. 2005; 25: 199-204Crossref PubMed Scopus (89) Google Scholar, 37Corbo J. Esses D. Bijur P.E. et al.Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache.Ann Emerg Med. 2001; 38: 621-627Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 38Shahrami A. Assarzadegan F. Hatamabadi H.R. et al.Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache.J Emerg Med. 2015; 48: 69-76Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Dihydroergotamine, an older medication, has mostly been supplanted by sumatriptan. Parenteral ondansetron and other serotonin-receptor antagonists have not been well studied in acute migraine. Intravenous fluid is commonly used for acute migraine but it is unclear whether it is of benefit.39Balbin J.E. Nerenberg R. Baratloo A. et al.Intravenous fluids for migraine: a post hoc analysis of clinical trial data.Am J Emerg Med. 2016; 34: 713-716Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar Fluids are best reserved for patients with overt signs of dehydration. Because they are generally well tolerated, various nerve blocks are sometimes used to treat acute migraine, although evidence supporting efficacy does not yet exist.40Ashkenazi A. Levin M. Greater occipital nerve block for migraine and other headaches: is it useful?.Curr Pain Headache Rep. 2007; 11: 231-235Crossref PubMed Scopus (91) Google Scholar Parenteral opioids have a complicated relationship with acute migraine. This class of medication is the most common one used to treat migraine in US EDs.2Friedman B.W. West J. Vinson D.R. et al.Current management of migraine in US emergency departments: an analysis of the National Hospital Ambulatory Medical Care Survey.Cephalalgia. 2015; 35: 301-309Crossref PubMed Scopus (62) Google Scholar Led by hydromorphone, opioids are used in slightly more than 50% of all migraine visits.40Ashkenazi A. Levin M. Greater occipital nerve block for migraine and other headaches: is it useful?.Curr Pain Headache Rep. 2007; 11: 231-235Crossref PubMed Scopus (91) Google Scholar Low-quality studies (nonexperimental design) have linked ED use of parenteral opioids to a variety of negative outcomes, including repeated ED visits and less responsiveness to triptans.41Friedman B.W. Vinson D.R. Convincing the skeptic. How to fix emergency department headache management.Cephalalgia. 2015; 35: 641-643Crossref PubMed Scopus (5) Google Scholar Regardless of whether these associations are true, opioids seem less likely to achieve the goals of sustained headache freedom and return to work and so should not be offered as first-line therapy to patients who present de novo to an ED with acute migraine and without contraindications to the therapies discussed above. Strategies for patients who insist on treatment with opioids are discussed elsewhere.42Prettypaul C, Friedman BW. Managing mirgraine headaches in complicated patients. 2016. Available at: https://www.aliem.com/2016/managing-migraine-headaches-complicated-patients/. Accessed July 3, 2016.Google Scholar The author’s stepwise approach for treatment of refractory acute migraine is presented in Figure 3. Migraine is a recurrent headache disorder. Patients are very likely to continue to experience headaches in the days, weeks, months, and years after ED discharge. Two thirds of ED patients with migraine experience headache during the 24 hours after discharge. Many of these headaches are functionally impairing or severe in intensity.43Friedman B.W. Hochberg M.L. Esses D. et al.Recurrence of primary headache disorders after emergency department discharge: frequency and predictors of poor pain and functional outcomes.Ann Emerg Med. 2008; 52: 696-704Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Parenteral dexamethasone is modestly effective at mitigating recurrence of moderate or severe headache within 72 hours of ED discharge (number needed to treat=9).44Colman I. Friedman B.W. Brown M.D. et al.Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence.BMJ. 2008; 336: 1359-1361Crossref PubMed Scopus (113) Google Scholar Naproxen 500 mg or sumatriptan 100 mg, to be used to treat the postdischarge headache, will improve some but not all of these headaches.45Friedman B.W. Solorzano C. Esses D. et al.Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan.Ann Emerg Med. 2010; 56: 7-17Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar An ED-based headache education program with specialist referral did not improve long-term headache outcomes among a general population of ED migraineurs.46Friedman B.W. Solorzano C. Norton J. et al.A randomized controlled trial of a comprehensive migraine intervention prior to discharge from an emergency department.Acad Emerg Med. 2012; 19: 1151-1157Crossref PubMed Scopus (11) Google Scholar This type of intervention is best reserved for patients with more complicated disease, including those with chronic migraine, psychiatric comorbidities, and concomitant medication overuse headache, a disorder defined by an upward spiral of increasing headache frequency in the setting of increased usage of analgesic or migraine medication, including nonsteroidal anti-inflammatory drugs, acetaminophen, opioids, and triptans.47Kristoffersen E.S. Lundqvist C. Medication-overuse headache: epidemiology, diagnosis and treatment.Ther Adv Drug Saf. 2014; 5: 87-99Crossref PubMed Scopus (83) Google Scholar Preventive medications, such as the β-blockers propranolol and metoprolol or the antiepileptic topiramate, are often considered for patients who continuously experience several days or more of migraine per week.48Pringsheim T. Davenport W. Mackie G. et al.Canadian Headache Society guideline for migraine prophylaxis.Can J Neurol Sci. 2012; 39: S1-59PubMed Google Scholar Cheaper Migraine Medication Just as Useful and ConvenientAnnals of Emergency MedicineVol. 69Issue 6PreviewI read with interest the excellent review article on migraine management by Friedman.1 I would like to share with readers a few tricks of the trade that I have learned through the years. Full-Text PDF