Comparing Treatments in the Emergency Department: What Works for Migraine?

Michael J. Marmura MD


Headache. 2021;61(4):567-568. 

Difficulties in treating patients with headache including migraine are a common conundrum for emergency department (ED) providers. Headache accounts for 3% of all ED visits in the United States or about 4 million visits per year.[1] While primary headache comprises the majority of ED encounters, nonspecific "headache" is the most common diagnosis. This implies migraine is significantly underdiagnosed by ED providers.[2]

In the ED, non-headache specialists must screen for secondary headache, confirm the diagnosis, and attempt to alleviate their patients' symptoms. ED providers do not typically receive training in the preventive, long-term management of migraine, and headache specialists are rare in underserved areas. Patients with chronic migraine or daily headache present an even bigger challenge.[3] Adding to this difficulty, the ED setting itself may trigger discomfort for those with photo- or phonophobia.

Evidence-based reviews and guidelines for acute migraine largely focus on the treatment of migraine attacks in patients with episodic migraine. Parenteral migraine treatments, given in infusion or ED settings, do not receive "Level A recommendations" due to the lack of Class I studies to support their effectiveness.[4] The majority of Class I studies focus on the treatment of acute migraine within hours of onset in patients with episodic disease. Even in these studies of carefully selected subjects, pain-freedom rates at 2 h fall below 50% of patients with the best acute therapies.[5] In clinical practice, the acute treatment of migraine depends on multiple factors such as severity, length of attack, and presence of other symptoms such as prolonged aura or allodynia. The optimal acute treatment for prolonged, severe migraine—as seen in the ED—is even less clear.

In this issue of Headache, Hodgson and colleagues present results from a prospective, randomized, double-blind, controlled, single-center trial comparing two common parenteral medications for migraine: chlorpromazine 12.5 mg and prochlorperazine 12.5 mg.[6] In addition to pain severity, the authors considered associated symptoms of migraine such as nausea severity, photophobia, and phonophobia. The investigators specifically screened for adverse events including vital signs and a formal akathisia rating scale. As with most ED studies, patients often presented with severe, prolonged attacks—with a mean of over 50 hours since headache onset. Many patients reported severe baseline pain prior to treatment with a pain score on arrival of over 7/10 in each group. While pain-freedom was not a primary endpoint, most patients improved with treatment. Pain reduction was 3.0 and 4.0 in the chlorpromazine group at 60 and 120 min, respectively, and 2.0 and 3.0 at 60 and 120 min in the prochlorpromazine group. There were nonspecific reductions in the chlorpromazine arm in median headache severity at 60 and 120 min and well as the need for rescue medication. Side effects were common, occuring in 50% and 21% of the chlorpromazine and prochlorperazine groups, respectively. In the chlorpromazine group, four subjects experienced postural hypotension and two had syncopal events. Studies such as this, especially those which compare treatments, offer insight into the challenging problem of managing migraine in the ED. While not statistically significant, these results suggest chlorpromazine should be considered for patients with severe migraine, while prochlopromazine appears less likely to cause serious adverse events.

While several studies have attempted to answer the question of what works for acute migraine in the ED, there are few guidelines for status migrainosus or ED treatment in general. Even when protocols do exist, clinicians do not always follow them.[7] An evidence-based assessment by Orr et al. graded only metoclopramide, prochlorperazine and subcutaneous sumatriptan as Level B recommendations, and dexamethasone as Level B to prevent headache recurrence.[8] In reality, ED providers frequently combine therapies such as diphenhydramine, antiemetics, non-steroidal anti-inflammatories, magnesium, anticonvulsants, dihydroergotamine, and even more aggressive therapies such as propofol[9] or ketamine.[10]

Given these challenges, here are a few suggestions for what we can do as headache experts to improve the care of migraine in the ED in the future:

  • Establish collegial relationships with ED providers. This could mean providing feedback, designing ED protocols at your institution, or making it easier for ED patients to establish outpatient care for migraine after discharge.

  • Educate ED providers about migraine. A key point to understand is that ED presentations for migraine are just a part of the underlying disease.[11] As part of these efforts, encourage ED providers to make a migraine diagnosis when it is appropriate, rather than non-specific "headache." Treatment in the ED should be aggressive when needed, but it helps to have realistic expectations about the potential for headache freedom.

  • Combining our experiences by collaborating and developing multicenter clinical trials for ED treatment. Multisite randomized clinical trials increase external validity and statistical power, and make recruiting easier.

  • Work closely with patients to improve their overall treatment including prevention. Effective preventive treatment may dramatically lower overall treatment cost and improves quality of life.

Migraine in the ED often represents the peak of an often-disabling disease, with patients at their most desperate and vulnerable. At the same time, an ED encounter can provide the opportunity for patients to better understand their disease, receive acute treatment that helps them return to function, and perhaps even establish care with an outpatient provider with an interest in migraine. As headache specialists, it is important to work with our ED peers to meet this challenge.