Migraine Treatment in the ED: Overcoming Our Penchant for Opioids

Headache is the fifth most common reason cited for visiting the emergency department (ED), and migraine accounts for at least 1.2 million annual ED visits.¹ Opioids are often used for migraine treatment in the ED, despite recommendations against their use as first-line therapy in this setting.² Likely in part as a result of this common practice, headache is the second most common symptom (after back pain) reported by drug seekers presenting to the ED.¹

In addition to the need to treat migraine more effectively, there is also a clear need to reduce the use of opioids both in these patients and in general. In response to the ongoing opioid crisis, ED physicians reduced their rates of opioid prescribing by 8.9% from 2007 to 2012, more than any other specialty.¹ To further reduce opioid prescription for migraine in the ED, effective alternatives should be identified.

A new review explores evidence supporting the efficacy of dopamine receptor antagonists in treating migraine.¹ “While still incompletely understood, it is hypothesized that metoclopramide aborts migraine headaches through inhibiting trigeminovascular activation [and] studies show that metoclopramide is as effective as sumatriptans in migraine pain relief,” the authors wrote. These agents are also associated with fewer adverse effects than other analgesics. Acute dystonic reactions, the most common adverse effect linked with metoclopramide and prochlorperazine, affect an estimated 1 in 500 patients.³

The review authors examined research comparing the efficacy of dopamine receptor antagonists to that of opioids for migraine treatment in the ED.¹ Their findings are summarized here:

• In a 2008 retrospective cohort study of patients >17 years of age receiving treatment for migraine in the ED (n=200), self-reported pain scores decreased by 3.7 points among those treated with metoclopramide vs 2.3 points for hydromorphone and 2.8 points for other agents such as sumatriptan, promethazine, and ibuprofen.⁴ Patients who received metoclopramide also used rescue medications less frequently and had faster times to discharge. “The authors concluded that 10 to 20 mg of metoclopramide [intravenously] is safe and effective for the initial treatment of migraine in the ED and may be more effective than hydromorphone,” according to the current review.
• A double-blind randomized controlled trial (n=127) compared prochlorperazine plus diphenhydramine to hydromorphone in patients ≥21 years of age with moderate or severe migraine. Sustained headache relief of 48 hours with 1 dose was reported by 60% of participants in the prochlorperazine group vs 31% of those receiving hydromorphone, with an absolute risk reduction of 28% (95% CI, 12%-45%) with prochlorperazine.⁵
• In a recent double-blind, randomized controlled trial, the average reduction in visual analog scale pain scores was 63.5 mm (95% CI, 52.7-74.3 mm) for patients who received prochlorperazine compared with 43.5 mm (95% CI, 30.2-56.8 mm) for those treated with ketamine (P =.03).⁶ The prochlorperazine group also had less use of rescue medications and lower rates of vomiting and subjective restlessness. When contacted 24 to 48 hours after discharge, 30% of patients in the prochlorperazine group still reported current headache vs 50% of those in the ketamine group.
• In a 2015 retrospective chart review of 574 patients presenting to the ED for primary headache, the odds of having an ED stay >6 hours were 3.9 times higher (95% CI, 2.5-6.1; P <.001) among patients treated with opioids (morphine, hydromorphone, and fentanyl) compared with those treated with nonopioids such as prochlorperazine, metoclopramide, acetaminophen, and triptan.⁷
• Other studies have found similar results linking opioids with increased length of hospital stay, a greater number of repeat visits, and increased need for rescue medications.¹

“While each of the studies in this review did have certain limitations, collectively they suggest that patients seen in the ED for migraine headache should be given metoclopramide or prochlorperazine as first-line abortive agents in order to achieve sustained patient relief and improved emergency department efficiency,” the authors concluded.

Neurology Advisor spoke with Mia T. Minen, MD, MPH, assistant professor of neurology and director of Headache Services at New York University Langone Medical Center in New York City, to further discuss issues pertaining to migraine treatment in the ED.

Neurology Advisor: What are your thoughts on why opioids are so often still used for these patients, and what is needed to help turn the tide toward clinicians using opioids less often for these patients, as well as safer alternatives more often?

Dr Minen: There is significant evidence that opioids are not the right treatment of choice for migraine in the ED. Benjamin Friedman, MD, published a study in Neurology in 2017 that showed this.⁵ In fact, the data safety monitoring board stopped the trial early because the results were so clear that opioids were not the right treatment for these patients.

I think opioids are still used for a variety of reasons:

• Some patients who have been receiving them before request them, not realizing the lack of efficacy and potential negative long-term effects.
• Opioids are significantly cheaper than the cost of triptans, the migraine-specific medications approved by the US Food and Drug Administration. This is truly unfortunate because there are 7 different triptans that work to stop migraine. They all work slightly differently, and patients may respond to them slightly differently. Typically, we like to trial the different triptans until we find the 1 that works best for the patient. Unfortunately, in a study we conducted, insurance companies posed significant limitations on triptans.⁸ There was substantial variation in coverage, and all plans imposed quantity limits on 1+ triptan formulations, with >80% imposing quantity limits on 14/19 formulations studied.
• We need to work on more dissemination and implementation of the evidence-based guidelines. We published the Migraine Action Plan, which is intended to help with this.⁹ The Migraine Action Plan provides instructions for therapies a patient might receive in the ED when they present for migraine care. 
• Providers do not realize that triptans are fairly safe medications that are available over the counter in some other countries. They are contraindicated if there is uncontrolled hypertension or prior history of stroke or heart attack. Also, they are relatively contraindicated in people older than 65 years. However, they are safe for most people.

Neurology Advisor: What are some of the most effective alternatives to opioids for treatment of migraine in the ED?

Dr Minen: There are published treatment guidelines for patients who present to the ED for migraine.² These were based on a systematic review of the literature, and the evidence was then graded by experts. The guidelines recommend intravenous metoclopramide and prochlorperazine and subcutaneous sumatriptan as first-line therapies for adults presenting to the ED with acute migraine (level B recommendation), and dexamethasone should be offered for prevention of headache recurrence (level B).

In addition, the guidelines state that 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” (level C recommendation).

Neurology Advisor: Are there additional treatment implications for clinicians that you would like to mention?

Dr Minen: It is very important for clinicians to realize that for the majority of people, after discharge from the ED, the headache returns. Thus, it is important to ensure that patients have a well thought-out discharge plan including a migraine abortive medication, not just an over-the-counter medication such as a nonsteroidal anti-inflammatory drug, and a treatment regimen that takes into account symptoms other than the headache.

Specifically, the discharge plan should include nonoral routes of administration if the patient has nausea and/or vomiting. Triptans come in nonoral forms, and antiemetics can be used. Migraine preventive treatments should also be considered. 

Neurology Advisor: What should be next steps in this area in terms of research or treatment policies?

Dr Minen:

• There should be additional communication between neurologists and ED providers.
• There is a need for advocacy by patients and clinicians to make the evidence-based treatments more accessible to patients.
• We need to consider the use of urgent care centers, which have not been well studied for migraine but have the potential to help patients, given that they are open on nights and weekends.
• We are now studying nonpharmacologic treatments for migraine in the ED as well. 

References

1. Dodson H, Bhula J, Eriksson S, Nguyen K. Migraine treatment in the emergency department: alternatives to opioids and their effectiveness in relieving migraines and reducing treatment times. Cureus. 2018;10(4):e2439.
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(6):911-940.
3. Guala A, Mittino D, Ghini T, Quazza G. Are metoclopramide dystonias familial? Pediatr Med Chir. 1992;14(6):617-618.
4. Griffith JD, Mycyk MB, Kyriacou DN. Metoclopramide versus hydromorphone for the emergency department treatment of migraine headache. J Pain. 2008;9(1):88-94.
5. Friedman BW, Irizarry E, Solorzano C, et al. Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology. 2017;89(20):2075-2082. 
6. Zitek T, Gates M, Pitotti C, et al. A comparison of headache treatment in the emergency department: prochlorperazine versus ketamine. Ann Emerg Med. 2018;71(3):369-377.
7. McCarthy LH, Cowan RP. Comparison of parenteral treatments of acute primary headache in a large academic emergency department cohort. Cephalalgia. 2015;35(9):807-815.
8. Minen MT, Lindberg K, Langford A, Loder E. Variation in prescription drug coverage for triptans: analysis of insurance formularies. Headache. 2017;57(8):1243-1251.
9. Peretz AM, Minen MT, Cowan R, Strauss LD. Introducing the migraine action plan. Headache. 2018;58(2):195.