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The Best Three Treatments for Migraine

Roberts, James R. MD

doi: 10.1097/01.EEM.0000529874.67226.e6

Dr. Robertsis a professor of emergency medicine and toxicology at the Drexel University College of Medicine in Philadelphia. Read the Procedural Pause, a blog by Dr. Roberts and his daughter, Martha Roberts, ACNP, PNP, at, and read his past columns at




Headache is a common ED presentation, and the diagnosis is relatively straightforward. It's not that difficult to make a diagnosis of headache caused by meningitis, intracranial hemorrhage, or brain tumor—tests can readily substantiate these diagnoses. Most causes of headache, however, are benign and only vaguely understood or accurately diagnosed in the ED.

Many patients are treated and released without a definitive diagnosis. Often patients are given a diagnosis of tension headache or sinusitis. Migraine headaches are quite common and the leading cause of the time that patients spend disabled. They often present classically, and can usually be handled with simple attempts at pain relief, but the first-time migraine headache is a challenge to emergency clinicians. Multiple treatment regimens are available, many with reasonable results, but the specific treatment is usually based on the preference of the individual provider.

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Managing Migraine

Friedman BW

Ann Emerg Med


Many articles and many different clinical approaches to acute treatment regimens for migraine headaches appear in the literature. Most articles and authors share somewhat common recommendations, and no one specific treatment regimen is recognized as the best. The medical literature has reported on the use of more than 30 drugs or drug combinations to treat acute migraines. An extensive review by the American Headache Society for treating acute migraines in the ED can be found in Headache. (2016;56[6]:911;

A number of medications have been recommended, but three basic classes of parenteral drugs are most commonly used for acute migraine: antidopaminergics, triptans, and nonsteroidal anti-inflammatory drugs.

Parenteral drugs are recommended for migraine in the ED regardless of which drug or combination is chosen. Oral drugs are not preferred because of migraine-induced vomiting and associated gastric stasis. Treatment is usually more effective if given early, so if a CT scan is being ordered to rule out other causes, give the antimigraine drug before the patient has to wait in radiology. Minor migraines are usually treated at home with simple OTC analgesics, but ED patients more often have severe symptoms and require additional interventions.

Antidopaminergics: Compelling clinical evidence supports the use of antidopaminergics as safe and effective therapy for acute migraine. The medications not only relieve migraine-associated nausea and gastroparesis, they also relieve the headache. Four antidopaminergics are most commonly used: metoclopramide (Reglan), prochlorperazine (Compazine), droperidol, and haloperidol (Haldol). It is unclear why these drugs are effective. Some data suggest that migraine is a dopaminergic phenomenon, but these data are not consistent. These drugs and migraines share equally complicated CNS physiology, and metoclopramide is considered most favorable for pregnant patients with migraines.

Although they are effective, the IV antidopaminergics often have extra pyramidal symptoms, most commonly akathisia, a syndrome of restlessness and agitation that can occur in as many as a third of the patients receiving these medications. Akathisia is short-lived, but it is very unpleasant, and when asked, patients would rather not take the specific culprit medication again.

The administration of IV diphenhydramine (Benadryl), an anticholinergic, seems effective for prophylaxis of akathisia, and the drug is often administered with the migraine treatment. The author of this paper said diphenhydramine is not indicated to prevent the akathisia of metoclopramide, although it is often used in conjunction with it. Diphenhydramine works well with prochlorperazine, and can also be used to treat dystonic reactions though they are uncommon. Fortunately, tardive dyskinesia, an irreversible motor disorder, has not been reported after an isolated dose of an antidopaminergic.

The standard dose of metoclopramide is 10 mg IV, and it can be repeated a number of times in the ED. Many clinicians, including myself, will start with a 20 mg initial dose. Ondansetron, which is often effective for nausea and vomiting, has not been shown effective for migraines.

Triptans: Triptans are serotonin receptor agonists that have been effective in treating migraines. The most used and available parenteral triptan is sumatriptan (Imitrex and others). The data on sumatriptan are quite favorable, with a number needed to treat of 2.5. The median time for relief of headache is 34 minutes, but sumatriptan does have some annoying side effects such as chest pain, flushing, and occasionally worsening of the headache. Patients who receive sumatriptan also often report a reoccurrence of headache within 24 hours. Overall, the antidopaminergics tend to be better tolerated than subcutaneous sumatriptan.

Non-Steroidal Anti-inflammatory: Ketorolac (Toradol) is used to treat migraines, but data supporting its benefit are less robust than the above interventions. Some have suggested combining ketorolac with the antidopaminergics or the triptans. Oral naproxen (500 mg) combined with sumatriptan, has been studied and found to be quite effective for migraines.

Drugs that have been used and have not been found to be particularly effective are antihistamines alone, ketamine, propofol, and magnesium. An older treatment, dihydroergotamine (DHE), has largely been replaced as a first-line intervention. It was effective, but its use has largely been supplanted by others drugs. DHE is still recommended for severe resistant migraine in the ED. A common combination is 1 mg IV DHE plus 10 mg IV prochlorperazine (both by slow IV drip), a regimen that I have used successfully for years. Intravenous fluids and a variety of nerve blocks have also been suggested, but are infrequently used in the ED.

Parenteral opioids are the most commonly used drugs to treat migraines in the ED, but they have a number of drawbacks. The ability of opioids to relieve migraine symptoms is slightly inferior to the medications already mentioned, and it's currently recommended by most authors that opioids should not be used as first-line therapy for patients in the ED. Parenteral hydromorphone (Dilaudid) and morphine are commonly administered in refractory cases.

About two-thirds of ED patients with migraines will experience headaches for 24 hours after discharge. The use of parenteral dexamethasone (Decadron) seems to be moderately effective at mitigating recurrence of headache. Dexamethasone prior to discharge at a dose of 10-20 mg IV is currently recommended by the American Headache Society to reduce migraine recurrence. Naproxen and oral sumatriptan can also be used for post-discharge headache. Those who have recurrent migraines should be referred to a neurologist for preventive medications, such as anti-epileptics and beta blockers. The author's preferred stepwise treatment of migraines is presented in the table.



Table A

Table A

Comment: The best initial intervention for acute migraine headache in the ED is not known. There is general agreement that opioids should not be first-line therapy, not only because they are not particularly effective, but also because of the potential abuse in someone with chronic headaches. Many of the annoying side effects of anti-migraine medications can be prevented by slow IV administration rather than by bolus IV doses.

A popular and rather common intervention is metoclopramide (Reglan). It is suggested that 10-20 mg (I prefer 20 mg) be administered over 15 minutes via an IV drip to minimize side effects. Some will add IV diphenhydramine to the initial metoclopramide dose. Alternatively, 10 mg of IV prochlorperazine (Compazine) over 15 minutes plus 25 mg of IV diphenhydramine is another common first approach. These drugs can be repeated once or twice every hour or so in the ED. Some physicians will add ketorolac to the second antidopaminergic drug, and others will use DHE as a 1 mg IV drip over 15 minutes.

Considering that many migraines occur after discharge, it is commonly suggested that all patients receive 10-20 mg of IV dexamethasone prior to discharge. This seems to decrease the recurrence rate, and it is extremely safe.

Opioids were always given for migraine headaches in the old days, but they have become almost forbidden now in the modern literature. I still believe that hydromorphone and morphine are acceptable in someone who does not have excellent relief with triptans, metoclopramide, or prochlorperazine. One just needs to be careful about potential addiction in patients with chronic pain. Intravenous acetaminophen is not commonly used, but some data support its use in treating migraines.

The article by the American Headache Society has an extensive review of at least 30 interventions that have been studied for migraines. Attempting to decide on the best anti-migraine treatment by a review of the literature is nearly impossible. The authors of the study reviewed here and the American Headache Society suggest one of the three initial treatment choices outlined above. All other interventions have less supportive evidence in the literature, but are commonly used successfully by individual practitioners. Most recommend that patients be placed in a quiet, dark room; sleep often augments the medications.

One of the common issues challenging clinicians is making the accurate diagnosis of migraine headache. It's relatively easy when the patient has a history and a similar attack brings them to the ED. A careful examination and history as well as the occasional CT scan are all within the realm of ED intervention, but don't expect miraculous and immediate relief of migraines from any single specific treatment. Ask the patient what has worked best for him in the past. Most are familiar with the various drugs.

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Recommendations of the American Headache Society

Recommendations: Intravenous metoclopramide, prochlorperazine, and subcutaneous sumatriptan should be offered to eligible adults who present to an ED with acute migraine (Should offer – Level B). Dexamethasone should be offered to these patients to prevent recurrence of headache (Should offer – Level B). Because of lack of evidence demonstrating efficacy and concern about sub-acute or long-term sequelae, injectable morphine and hydromorphone are best avoided as first-line therapy (May avoid-Level C). (Headache 2016,56[6]:911;

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