Severe Migraine: Options for Acute Therapy in the Emergency Department

March 2, 2006

Seymour Diamond, MD, Betsy J. Pepper, MD

A 36-year-old man with a 15-year history of episodic migraine presents to the emergency department (ED) at 5 AM witha right-sided throbbing headache of 4 hours' duration. The headache awakened him, which is typical of his more severemigraine attacks. Unfortunately, the patient forgot to refill his prescription for pain medication and did not "catch" thisheadache in time. He took an over-the-counter combination of aspirin and caffeine, which seemed to help for about 60minutes, but the headache has returned full force. He has vomited twice-another characteristic typical of his migraineattacks

THE DIALOGUE:Clinician: This patient, who has an established diagnosis ofmigraine, appears to be overusing ED services. What isthe most appropriate way to help him without encouragingrepeated visits?

Headache specialist: If the headache pattern is typical andthe physical examination is normal, the first step is to determinewhich medications the patient has previouslyused to control the headaches acutely and when he lasttook medication to abort a headache.

Clinician: How will that information help guide treatment?

Headache specialist: It can help you determine whether histherapeutic regimen is suboptimal and why headache controlis less than ideal. For example, this patient may have usedonly nonspecific medications, such as narcotics or butalbitalcombinations. The goal is to find an option for this patientthat will allow him to function well for the rest of the day.

Clinician: Why is it important to know when this patientlast took medication for his headache?

Headache specialist: It can give you clues as to whetherthe patient is overusing an abortive medication, which canlead to rebound headache. This is a state of refractory, increasinglyresistant headaches that recur as soon as thepatient's blood level of the overused or abused agent decreasesbelow a certain point.

You need to ascertain that this patient is not usingabortive medications too frequently or inappropriately.You would not want to treat the patient with a medicationthat he has previously overused or with an agent incompatiblewith a drug that he has ingested recently.

Clinician: What are the most appropriate options for thispatient?

Headache specialist: The best would be an agent thatacts directly on the mechanism of migraine-ideally, aserotonin agonist. This type of drug is migraine-specificand acts directly on the 5-HT1B or 5-HT1D receptorsites on neural and vascular tissues to inhibit the nociceptivecycle, reverse abnormal meningeal blood vesseldilation, quiet perivascular inflammation, and relieve theneurologic and GI accompaniments of the migraine.The medications in this group include dihydroergotamine(DHE), an ergotamine derivative, and the triptans.Five triptans are currently available in the United States;however, only the nonoral formulations are appropriate ina patient who is vomiting and who also needs immediatepain relief.

Clinician: Are DHE and the triptans appropriate for any patientwho presents with migraine in the ED?

	Table 1 –Contraindications to ergotamines and dihydroergotamine
Uncontrolled hypertension Coronary artery disease Prinzmetal angina Peripheral vascular disease Cerebrovascular disease Hepatic or renal disease Active sepsis Pregnancy and lactation (category X) Complicated migraine Concomitant triptan use within 24 hours Concomitant macrolide antibiotics Concurrent infection Age > 60 y (relative contraindication)

Headache specialist: There are contraindications (Tables1 and 2). Patients with uncontrolled hypertension are atrisk because the vasoconstrictor effect of serotonin ago-nists can further increase blood pressure. Similarly, patientswith coronary artery disease should not use ergotaminesor triptans because these agents constrictcoronary and cerebral blood vessels. Triptans are lesslikely than DHE to affect the coronary vessels; for example,subcutaneous (SC) sumatriptan is associatedwith about a 15% decrease in coronary diameter. However,even a small reduction in coronary diameter couldbe fatal in a patient with significant coronary atherosclerosisor Prinzmetal angina.

Do not give serotonin agonists to:

Patients with significant risk factors for coronary arterydisease or stroke.
Those who have complicated migraine with stroke-likesymptoms.
Persons older than 60 years.

DHE is contraindicated during pregnancy becauseof its oxytocic effects. Triptans have not been thoroughlyevaluated for use during pregnancy. DHE should be avoidedin patients with a history of deep venous thrombosis,significant liver disease, or concurrent infections.

Clinician: What regimen and route of administration doyou recommend?

Headache specialist: DHE is probably most effectivewhen given intravenously, preceded by an antiemetic.The initial test dose is 0.5 mg diluted in 50 mL of normalsaline or dextrose 5% in water, to be infused over 30minutes. Subsequent doses can be increased to 1 mg.DHE can be administered via IV push, although thisroute increases the risk of nausea. DHE can also begiven at a dose of 1 mg SC; 1 mg IM is even more effective.Possible side effects include leg cramps, jointaches, and diarrhea. Subcutaneous DHE is effective in70% to 75% of patients.

Sumatriptan is used in the ED because it is the onlytriptan that can be given parenterally. The preferred dosein this setting is 6 mg SC, although the nasal spray, availablein a 20-mg formulation, may also be effective quickly.The average time to onset for sumatriptan SC is about 10minutes and for sumatriptan nasal spray about 15 minutes.The earlier in the attack sumatriptan is given, the greaterthe likelihood of pain relief.

	Table 2 – Contraindications to triptans
Uncontrolled hypertension Coronary artery disease Cerebrovascular disease Prinzmetal angina Complicated migraine Pregnancy and lactation (category C) Concomitant ergotamine use within 24 hours Severe hepatic or renal impairment Age > 60 y (relative contraindication)

Clinician: Can I safely use a triptan if the ergot does notwork-or vice versa?

Headache specialist: No-an ergot and a triptan cannot beused within the same 24-hour period. This is one of thereasons that we need to inquire about medications the patientmay have used before arriving at the ED.

Clinician: What if the patient has already failed to respondto a triptan or ergotamine that was self-administered athome, or if he or she is not a suitable candidate for eitherform of therapy?

Headache specialist: Several options are still available. Fora patient who wants to remain alert after treatment, parenteralketorolac-an effective analgesic that is usuallynonsedating-is an excellent alternative. The recommendeddoses are 30 mg IV or 60 mg IM.Occasionally, magnesium sulfate, 1000 mg IV, willabort a severe headache without sedating effects. Val-proate acid, 1000 mg IV, administeredfairly rapidly over 15 minutes, is anotheralternative.

Clinician: I see an occasional patientfor whom none of these drugs areeffective-and the rare patient whois allergic to all of these medications.What do you recommend in thissetting?

Headache specialist: If your hospitalpharmacy supplies it, parenteral orphenadrine,30 to 60 mg IM or IV, ishighly effective in certain patients. This agent has an antihistamineeffect that may be slightly sedating. Hydroxyzine,50 to 75 mg IM (without the narcotic component),may be effective, although this agent is also sedating.

	Table 3 - Acute migraine options in the emergency department*
Prochlorperazine, 10 mg IV or IM

Chlorpromazine, 25 - 50 mg IM or slow IV infusion over 15 to 20 min

Droperidol, 1.25 - 2.5 mg IV

Haloperidol, 2 - 5 mg IM

*All of these agents can be used concomitantly with benztropine mesylate, 1 - 2 mg IM, or diphenhydramine, 25 - 50 mg IM or IV.

The most sedating of the non-narcotic agents foraborting migraine are the phenothiazines, which areprobably effective because they act on several neurotransmitters,including dopamine and possibly serotonin.The phenothiazines are anxiolytic and some are potentantiemetics. Suggested agents and doses are listed inTable 3. The agents used most frequently in the EDare chlorpromazine and prochlorperazine. Patients whoreceive intravenous chlorpromazine must be monitoredfor hypotension and peripheral vein irritation. Alternativesare intravenous droperidol or intramuscular haloperidol.Adverse effects, such as muscle spasm or dystonicreaction, can be treated with benztropine mesylate,1 to 2 mg IM, or diphenhydramine, 25 to 50 mg IV.

Clinician: I find that some patients become very "antsy"and uncomfortable following intravenous administration ofa phenothiazine.

Headache specialist: Lorazepam, 1 to 2 mg IM or IV,may provide relief. Of course, respiratory status must bemonitored. Akathisias from phenothiazine treatment areextremely uncomfortable and must be treated promptly.

Clinician: What do you recommend if, in spite of everythingthat has been tried, the patient still says that his painhas not been relieved and demands a narcotic?

Headache specialist: If you feel that the patient is reliable,it is perfectly appropriate to administer a powerful analgesicon the rare occasion when all else fails.The longest-acting narcotic, methadone, can beadministered at a dose of 10 mg IM with an antiemetic.This drug has a 6-hour half-life. The short-acting narcotics(meperidine, nalbuphine, and butorphanol) wear offalmost before the patient is discharged from the ED. Theproblem with narcotics, of course, is the associated disabilitythat prevents the patient from functioning fully. Inorder not to interfere with the primary physician's underlyingtreatment plan, do not give the patient a dischargeprescription for more than 4 to 6 narcotic pills. Follow-upwith the primary physician or appropriate referral physicianis mandatory.

Clinician: What if I suspect a patient is overusing the EDfor secondary purposes, such as obtaining narcotics?

Headache specialist: You have no obligation to providetreatment that you deem inappropriate simply becausethe patient requests it. I would suggest drug-dependencecounseling. If you feel the patient may be addicted, consideradmitting him for detoxification or refer him to a specialtyheadache clinic.

FOR MORE INFORMATION:

Diamond S, Pepper BJ. Severe acute headache: step by step through theworkup. Consultant. 2001;41:1329-1332.