Treatment of Acute Migraine Pain in the Emergency Department


A new study makes the case for alternatives to opioids in the treatment of migraine.

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Welcome to Neurology Times. I’m Dr. Andrew Wilner and today I’d like to discuss the treatment of acute migraine pain in the emergency department.

Migraine patients visit the emergency department 1.2 million times/year in the US. More than half of these patients received parenteral opioids. Despite the lack of randomized studies to support the use of hydromorphone in acute migraine, this opioid is employed in 25% of ER migraine visits, or more than ¼ million doses per year.

A recent review evaluated 68 randomized controlled clinical trials of a variety of parenteral medications available for acute migraine pain control.2 The study concluded that intravenous metoclopramide, prochlorperazine, and sumatriptan should lead the list of medications to relieve acute headache pain in the emergency room setting (Level B). The authors also stated that injectable morphine and hydromorphone should be “avoided as first-line therapy” (Level C).

Prochlorperazine vs hydromorphone
A recent randomized, double blind study performed in 2 emergency departments in New York City compared the effectiveness of IV prochlorperazine 10 mg plus diphenhydramine 25 mg over 5 minutes, vs. IV hydromorphone 1 mg plus normal saline placebo over 5 minutes for adults with moderate to severe migraine pain.1  The diphenhydramine was added to prevent akathisia. Patients who had used opioids in the previous 30 days, had histories of addiction, or prior methadone use were excluded.

Out of 1058 patients initially evaluated, only 127 met all the inclusion/exclusion criteria. These included 63 patients (50 females, mean age 32) randomized to the prochlorperazine group and 64 patients (56 females, mean age 35) randomized to the hydromorphone group. The data monitoring committee halted enrollment when it became clear that the prochlorperazine group had overwhelmingly superior results.

The primary outcome of sustained headache relief for 48 hours after 1 medication dose was met by 37/62 (60%) of the prochlorperazine group but only 20/64 (31%) of the hydromorphone group.

The difference between the groups was 28% with a number needed to treat (NNT) of 4.

In addition, only 6% of prochlorperazine patients requested a second dose of study medication vs. 31% of hydromorphone patients.

Patients in the prochlorperazine group spent a median of 105 minutes in the emergency department vs 193 minutes for those in the hydromorphone group.

The most common side effects were:
Anxiety or restlessness in 5% of the prochlorperazine group
Dizziness or weakness in 14% of the hydromorphone group

At 48 hours, the incidence of restlessness and drowsiness was similar in both groups. There was no difference in long-term follow up at 1 and 3 months with respect to headache days, return visits to the emergency department, and functional disability scores.

This study provides Class I evidence that prochlorperazine is superior to hydromorphone for the acute treatment of migraine pain in the ER. It provides practice changing guidance for emergency department physicians. The results also constitute one more reason not to use an opioid, avoiding the risks and restrictions that come with this class of drugs. However, the study results do not prohibit the use of opioids, particularly for patients who fail to respond to antidopaminergics such as prochlorperazine.

Thank you for listening. I’m Dr. Andrew Wilner, reporting for Neurology Times. For more updates, follow me on Twitter @drwilner. Thank you.




Dr. Wilner's latest book, Bullets and Brains, is a collection of over 100 essays that focus on the intersection of neurology and society. Twitter: @drwilner.


1. Friedman BW, Irizarry E, Solorzano C et al. Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology 2017;89:1-8.

2. 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.

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