What Inpatient Treatments Do We Have for Acute Intractable Migraine?

3-minute consult on general principles, recommendations, available options

By Ashhar S. Ali, DO, and Mark Stillman, MD

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For acute intractable migraine, we recommend the following combination treatment:

  • Normal saline (0.9 percent NaCl) 1 to 2 liters by intravenous (IV) infusion over 2 to 4 hours. This can be repeated every 6 to 12 hours.
  • Ketorolac 30-mg IV bolus, which can be repeated every 6 hours. However, patients with coronary artery disease, uncontrolled hypertension, acute renal failure or cerebrovascular disease should instead receive acetaminophen 1,000 mg, naproxen sodium 550 mg or aspirin 325 mg by mouth.
  • Prochlorperazine or metoclopramide 10-mg IV infusion. This can be repeated every 6 hours. However, to reduce the extrapyramidal adverse effects of these drugs, patients should first receive diphenhydramine 25- to 50-mg IV bolus, which can be repeated every 6 to 8 hours.
  • Sodium valproate 500 to 1,000 mg by IV infusion over 20 minutes. This can be repeated after 8 hours.
  • Dexamethasone 4-mg IV bolus every 6 hours, or 10-mg IV bolus once in 24 hours.
  • Magnesium sulfate 500 to 1,000 mg by IV infusion over 1 hour. This can be repeated every 6 to 12 hours.

If the migraine has not improved after three cycles of this regimen, a neurologic consultation should be considered. Other options include dihydroergotamine and occipital nerve blocks1 performed at the bedside.

General principles

Managing acute intractable migraine can be frustrating for both the practitioner and the patient. The following general principles are helpful.

Use a combination of drugs. Aborting a severe migraine attack often requires a combination of medications that work synergistically.

Use IV and intramuscular formulations rather than oral formulations: They are more rapidly absorbed, provide faster pain relief and can be given when the nausea that often accompanies migraine precludes oral treatments.

Rule out secondary causes. The mnemonic SNOOP — systemic signs, neurologic signs, onset, older age, progression of existing headache disorder — is useful for assessing underlying causes.2 Any patient presenting with intractable migraine should also have a thorough neurologic examination.

Screening electrocardiography may be helpful, as the pretreatment QTc interval may direct the choice of IV treatment. If the patient has a prolonged QTc or is taking another drug that could prolong the QTc, certain medications, specifically dopamine receptor antagonists and diphenhydramine, should be avoided.

Ask the patient what has worked previously. A particular agent may have been effective in aborting the migraine; thus, a single dose of it could abort the headache, expediting discharge.

Establish whether a triptan or ergot derivative has been used during the 24 hours before presentation, as repeated dosing within this interval is not recommended.3

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Establish the baseline headache severity. Complete headache relief is difficult to achieve in a patient with chronic daily headache, and establishing a more realistic goal (e.g., 50 percent relief) from the outset is useful.

Options for drug therapy

Antiemetics. Dopamine receptor antagonists are assumed to merely treat nausea in patients with migraine; however, they act independently to abort migraine and thus should be considered irrespective of the presence of nausea.

The two most commonly used agents are prochlorperazine and metoclopramide. The American Academy of Neurology guidelines recommend prochlorperazine as first-line therapy for acute migraine. Metoclopramide is rated slightly lower and is considered to have moderate benefit.4 The Canadian Headache Society cites a high level of evidence supporting prochlorperazine and a moderate level of evidence supporting metoclopramide.5 The American Headache Society assessment of parenteral pharmacotherapies gives prochlorperazine and metoclopramide a level B recommendation of “should offer” (a recommendation only additionally assigned to subcutaneous sumatriptan).3 Hence, either agent can be used.

To reduce the risk of post-treatment akathisia, diphenhydramine or benztropine may be given before starting a dopamine receptor antagonist. Diphenhydramine may be independently effective in migraine treatment,6,7 but data on this are limited.

Ketorolac, ibuprofen. Ketorolac and ibuprofen are the only available nonsteroidal anti-inflammatory drugs (NSAIDs) for IV administration. The Canadian Headache Society guidelines strongly recommend ketorolac for the treatment of migraine in emergency settings.5 Doses range from 30 to 60 mg.1 Ibuprofen 400 to 800 mg by IV infusion is an acceptable alternative. These medications should be avoided in patients with renal failure or severe coronary artery disease.

Oral naproxen sodium is a possible alternative in patients with cardiovascular disease, as it has been shown to carry a lower cardiovascular risk than other NSAIDs.8

The same concerns in patients with renal dysfunction apply to any NSAID, as the enzyme cyclooxygenase plays a constitutive role in glomerular function.

Antiepileptic drugs. The antiepileptic drugs sodium valproate and levetiracetam are available in IV formulations that have demonstrated efficacy in the treatment of status migrainosus1 (i.e., migraine lasting more than 72 hours). Valproate has the strongest track record, is well tolerated and is effective in rapidly aborting migraine.9

Volume repletion. Although its use is anecdotal and to date no trial has measured its efficacy, IV volume repletion is often used in acute migraine, as most headache experts surmise it to be highly effective, especially in patients with prolonged nausea or vomiting.1

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Magnesium. IV magnesium is effective, particularly for migraine with aura.10 Hypotension is a common side effect, and pretreatment or concurrent treatment with IV fluids is advised. Doses from 500 to 1,000 mg have demonstrated efficacy.10

Corticosteroids. Corticosteroids can be used in the treatment of status migrainosus. Most studies have shown benefit in preventing recurrences rather than merely aborting migraine.11 A systematic review suggested that recurrent headaches are milder with corticosteroid treatment; 19 of 25 studies indicated favorable benefit, and 6 of 19 studies indicated noninferior outcomes.12

Both IV methylprednisolone and IV dexamethasone may be considered.12 Dexamethasone appears to be particularly effective in preventing headache recurrence when combined with other IV therapies.13 It can be given as a single dose of 10 mg, or as repeated doses of 4 mg up to 16 mg/day.1 Patients with active psychosis or uncontrolled diabetes should be closely monitored for these conditions, which corticosteroids can worsen.

Serotonergic agents. Serotonin agonists including subcutaneous sumatriptan and IV dihydroergotamine are highly effective, with proven statistical and clinical benefit.4  They should be considered in patients with no known history of coronary artery disease or other vaso-occlusive vascular disorder.1

Ideally, IV dihydroergotamine should be administered after consultation with a neurologist or headache specialist, given the pretreatment and co-treatment requirements often necessary to suppress its side effects. Careful titration is important to prevent transient headache exacerbations during infusion, as well as abdominal cramping, nausea and diarrhea.

Avoid opioids. Opioids should be avoided. Evidence supporting their use in acute migraine is extremely limited,3 and the risks of addiction and of migraine becoming chronic are high.14 Safer, more effective alternatives have been detailed above.

A detailed algorithm for the management of patients with acute migraine has been published14 and is aimed at decreasing acute treatment with opioids and barbiturates.

This article is reprinted from the July 2018 issue of the Cleveland Clinic Journal of Medicine (2018;85:514-516).

References

  1. Rozen TD. Emergency department and inpatient management of status migrainosus and intractable headache. Continuum (Minneap Minn). 2015;21:1004–1017. doi:10.1212/CON.0000000000000191
  2. Dodick D. Headache as a symptom of ominous disease. What are the warning signals? Postgrad Med. 1997;101:46-64. doi:10.3810/pgm.1997.05.217
  3. Orr SL, Friedman BW, Christie S, et al. Management of adults with acute migraine in the emergency department: the American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2016;56:911-940. doi:10.1111/head.12835
  4. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754-762. doi:10.1212/WNL.55.6.754
  5. Orr SL, Aubé M, Becker WJ, et al. Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings. Cephalalgia. 2015;35:271-284. doi:10.1177/0333102414535997
  6. Swidan SZ, Lake AE 3rd, Saper JR. Efficacy of intravenous diphenhydramine versus intravenous DHE-45 in the treatment of severe migraine headache. Curr Pain Headache Rep. 2005;9:65-70. doi:10.1007/s11916-005-0077-5
  7. Marmura MJ, Goldberg SW. Inpatient management of migraine. Curr Neurol Neurosci Rep. 2015;15:13. doi:10.1007/s11910-015-0539-z
  8. Farkouh ME, Greenberg BP. An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol. 2009;103:1227-1237. doi:10.1016/j.amjcard.2009.01.014
  9. Stillman MJ, Zajac D, Rybicki LA. Treatment of primary headache disorders with intravenous valproate: initial outpatient experience. Headache. 2004;44:65-69. doi:10.1111/j.1526-4610.2004.04010.x
  10. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache. 2015;55:3-20. doi:10.1111/head.12499
  11. Colman I, Friedman BW, Brown MD, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008;336:1359-1361. doi:10.1136/bmj.39566.806725.BE
  12. Woldeamanuel YW, Rapoport AM, Cowan RP. The place of corticosteroids in migraine attack management: a 65-year systematic review with pooled analysis and critical appraisal. Cephalalgia. 2015;35:996-1024. doi:10.1177/0333102414566200
  13. Singh A, Alter HJ, Zaia B. Does the addition of dexamethasone to standard therapy for acute migraine headache decrease the incidence of recurrent headache for patients treated in the emergency department? A meta-analysis and systematic review of the literature. Acad Emerg Med. 2008;15:1223-1233. doi:10.1111/j.1553-2712.2008.00283.x
  14. Ahmed ZA, Nacopoulos DA, John S, et al. An algorithm for opioid and barbiturate reduction in the acute management of headache in the emergency department. Headache. 2017;57:71-79. doi:10.1111/head.12961

Dr. Ali completed a fellowship in headache and facial pain at Cleveland Clinic in 2017; he is now a staff physician in the Division of Headache and Facial Pain, Department of Neurology, Henry Ford Hospital, Detroit. Dr. Stillman is a staff physician in the Center for Neurological Restoration in Cleveland Clinic’s Neurological Institute.