1. Jesani, Jennifer MSN, RN, FNP-BC, CEN
  2. Simerson, Darlie DNP, APRN, FNP-BC, CEN


Migraine headaches account for approximately 1.2 million emergency department (ED) visits annually. Despite the prevalence of this condition, there is little consensus on the best pharmacotherapeutic interventions to use in the ED setting. Guidelines published by the American Headache Society and the Canadian Headache Society offer some direction to ED providers but are not widely utilized. This article reviews the best evidence behind some of the medications frequently used to treat acute migraines in the ED setting, including dopamine receptor antagonists, serotonin receptor agonists, anti-inflammatory medications, opioids, magnesium, valproate, and propofol. The evaluation of patients presenting to the ED with an acute headache, the diagnostic criteria for migraines, and implications for advanced practice are also discussed.


Article Content

MIGRAINE HEADACHES cause debilitating pain and often lead sufferers to seek relief in the emergency department (ED). It is estimated that migraines affect 18% of women and 6% of men in the United States. Headaches are the fifth most common reason for ED visits, and about 5 million ED visits annually are attributable to headaches (Minen, Tanev, & Friedman, 2014). Approximately 1.2 million of these visits are due to acute migraines (Orr et al., 2016). By the time patients with an acute migraine arrive in the ED, many have attempted treatment with over-the-counter analgesics and have received minimal relief. This leads ED providers to select pharmacologic therapies with a rapid onset of action. Despite the burden migraine management places on ED providers, there is little consensus on the best medications to use. In practice, more than two dozen different medications are commonly used to treat migraines (Minen et al., 2014). Determining the optimal medications to use, especially after many patients have tried initial therapy and failed, presents a challenge to ED providers. The purpose of this review is to discuss the pharmacologic management of acute migraines in the ED and assess the evidence behind some of the medications used, including dopamine receptor antagonists, serotonin receptor agonists, anti-inflammatories, opioids, magnesium, valproate, and propofol.



Any patient who presents to the ED for an acute headache should receive a thorough medical evaluation to determine the cause of the pain. The differential diagnoses for acute headaches in the ED include both primary headache disorders and secondary causes of headache. Primary headache disorders include migraine, cluster, and exertional headaches and account for the majority of all severe headaches. Secondary headaches, which are attributable to an underlying intracranial process, account for only 5% of all severe headaches (Levin, 2015). Providers should exclude any secondary causes of headache through a detailed history, physical examination, and diagnostic testing if necessary before treating the patient for a primary headache.


Certain clinical and historical features should raise concern for underlying pathology. The presence of certain symptoms such as an abrupt onset of a "thunderclap" headache, neurological deficits, altered mental status, worsening pain with position changes or Valsalva, fever, and meningeal signs is a "red flag" feature that will require the provider to further investigate the cause of the symptoms and consider neuroimaging (Tintinall et al., 2016). The examination should include a complete head, neck, and neurological assessment. The funduscopic examination can determine whether acute angle-closure glaucoma or increased intracranial pressure is present (Levin, 2015). A medication history determines whether medication side effects or overuse is contributing to symptoms.


Determining the need for neuroimaging studies depends on the level of suspicion for an acute underlying process. The primary reason to obtain imaging in the ED is to identify the presence of a treatable lesion, such as tumors, vascular malformations, subarachnoid hemorrhage, aneurysms, cerebral venous sinus thrombosis, subdural and epidural hematomas, infections, stroke, or hydrocephalus (Edlow, Panagos, Godwin, Thomas, & Decker, 2008). The most common imaging study utilized is noncontrast head computed tomography, but other modalities such as computed tomographic angiography or magnetic resonance imaging may be useful. However, the use of computed tomography may be overutilized as 95% of all acute headaches are found to have a benign cause (Levin, 2015). It can be difficult for providers to determine which patients would benefit from neuroimaging. Because of these challenges, the American College of Emergency Physicians has published a clinical policy to guide this decision process (Edlow et al., 2008; see Table 1).

Table 1 - Click to enlarge in new windowTable 1. American College of Emergency Physicians recommendations for headache neuroimaging in the emergency departmenta


Once acute secondary causes of headache have been ruled out, providers may then proceed in treating primary headache disorders. Although there are several types of primary headache disorders, migraines are the most common encountered in the ED setting. The International Headache Society (IHS) lists diagnostic criteria for all headaches, including migraines (IHS, 2013). The two major subtypes of migraines are "migraine without aura" and "migraine with aura." According to the criteria, providers can make a diagnosis of migraine without aura if the patient has had at least five attacks of a headache that each last 4-72 hr and are associated with at least two of the following criteria: unilateral location, pulsating quality, moderate or severe pain intensity, or aggravation by routine physical activity that results in avoidance of those activities. The headache must also be associated with either nausea/vomiting or photo/phonophobia (IHS, 2013; Tintinalli et al., 2016). Migraine attacks may also present with cranial autonomic symptoms such as conjunctival injection, eyelid edema, miosis, ptosis, lacrimation, or nasal congestion. Cutaneous allodynia, which is severe pain to touch that is out of proportion to the stimulus, may also occur during attacks (IHS, 2013).


Migraines with aura are characterized by a fully reversible aura with visual, sensory, speech, motor, brainstem, or retinal symptoms. In addition to meeting the diagnostic criteria for migraine without aura, migraines with aura must also exhibit unilateral aura symptoms that spread gradually over more than 5 min and last no more than 60 min and are followed by a headache within 60 min. Visual auras are most common and often manifest as zigzag figures near the point of central vision. Sensory auras are the second most common and may manifest as unilateral paresthesia (IHS, 2013).



To better appreciate how pharmacotherapy for migraine management may be effective, it is important to have an understanding of the underlying pathophysiology of migraines. Migraines, though typically thought of as a vascular disorder causing dilation of the cranial vasculature, also involve peripheral and central sensitization of neurologic pain pathways. The pain associated with migraines is caused by activation of the trigeminovascular system. When the blood vessels in the pia mater and dura mater are affected by traction, dilation, or distension, pain signals are transmitted to the trigeminal nerve (Edlow et al., 2008; Kelley & Tepper, 2012a).


It is thought that both dopaminergic and serotonergic pathways are involved in the process. During peripheral sensitization, afferent neurons become irritated and begin rapidly firing in response to dilation of meningeal blood vessels. The result is a neurogenic inflammatory response involving the release of inflammatory cytokines, vasodilators, and histamine. The patient becomes more sensitive to the slight increase in intracranial pressure caused by the vasodilation, resulting in the throbbing quality of migraines. Central sensitization occurs when there is a reduction in the excitatory thresholds of cervical spine neurons, resulting in a pain response to a normally nonpainful stimulus in the scalp, face, or arms (Kelley & Tepper, 2012a). Treatments for acute migraine often attempt to modify these neurologic and vascular pathways by targeting neurotransmitter receptors that play a role in rapid neuron firing or by targeting the inflammatory response that results in intracranial vasodilation.



Many organizations have developed guidelines that focus on migraine prevention and treatment in the outpatient setting and are less applicable to the ED setting (Evers et al., 2009; Marmura, Silberstein, & Schwedt, 2015; Silberstein et al., 2012). Currently, the American Headache Society (AHS) and the Canadian Headache Society (CHS) have recommendations on the treatment of migraine specific to the ED setting (Orr et al., 2015; Orr et al., 2016). Despite these guidelines, ED providers' practice is variable and evidence-based treatment options are not always utilized (Friedman et al., 2015). This may be partly due to limited dissemination of these guidelines to emergency providers or lack of familiarity with certain treatment options. This article presents current evidence behind medications commonly used to treat acute migraines in the ED and incorporates the recommendations from two ED-specific guidelines for migraine treatment (see Table 2).

Table 2 - Click to enlarge in new windowTable 2. Select recommendations of the American Headache Society and the Canadian Headache Societya

Dopamine Receptor Antagonists

Dopamine receptor antagonists include phenothiazines such as prochlorperazine, chlorpromazine, and promethazine; butyrophenones such as haloperidol and droperidol; and antiemetics such as metoclopramide. It is thought that these medications antagonize dopamine receptors on postsynaptic cells in the limbic system and basal ganglia and have antiadrenergic, anticholinergic, and antiserotonergic effects. Although development of a prolonged QT interval is rare, the providers should take measures to avoid use in patients with a corrected QT interval of greater than 450 ms (Kelley & Tepper, 2012b).


There is a large body of evidence supporting the use of dopamine receptor antagonists for acute migraines. One randomized controlled trial (RCT) aimed to compare prochlorperazine with hydromorphone in the management of acute migraines. Adult participants in the study were randomized into one of two treatment groups: prochlorperazine 10 mg iv plus diphenhydramine 25 mg iv or hydromorphone 1 mg iv. Within 1 hr of treatment, 84% of participants in the prochlorperazine plus diphenhydramine treatment group reported either no or mild headache, whereas only 51% of participants in the hydromorphone group reported no or mild headache. Sustained headache relief after 48 hr was achieved by nearly double the number of participants in the prochlorperazine plus diphenhydramine group compared with the hydromorphone group. The authors concluded that prochlorperazine plus diphenhydramine results in statistically significant headache reduction over hydromorphone in the ED setting (Friedman et al., 2017).


Another RCT aimed to compare prochlorperazine with ketamine for the treatment of benign headaches in the ED. Adult participants in the study were randomized into two treatment groups: prochlorperazine 10 mg iv plus diphenhydramine 25 mg iv or ketamine 0.3 mg/kg iv plus ondansetron 4 mg iv. The participants in the prochlorperazine plus diphenhydramine arm reported a statistically significant decrease in pain compared with participants in the ketamine arm. After 24-48 hr, the participants in the prochlorperazine group reported higher levels of satisfaction with the medication and less headache relapse than those in the ketamine group. The authors concluded that prochlorperazine is more effective and better tolerated than ketamine for acute primary headaches in the ED (Zitek et al., 2017).


One RCT compared the efficacy of two different dopamine receptor antagonists. The participants were randomized into two treatment groups: metoclopramide 10 mg iv or haloperidol 5 mg iv. The participants in both groups also received diphenhydramine 25 mg iv to prevent possible akathisia. Both groups demonstrated statistically significant reduction in pain from baseline. When compared with each other, there was no difference in outcomes between groups and both medications were determined to be equivalent. On follow-up, 92% of participants in the haloperidol group reported satisfaction with treatment compared with 75% in the metoclopramide arm. The authors concluded that both metoclopramide and haloperidol are effective in treating migraines in the ED, and haloperidol may be better tolerated (Gaffigan, Bruner, Wason, Pritchard, & Frumkin, 2015).


A comparative efficacy clinic trial studied three different medications used to treat migraines to determine whether one resulted in greater headache relief than the other two. The participants were randomized into three treatment groups: valproate 1 g iv, metoclopramide 10 mg iv, and ketorolac 30 mg iv. The participants who received metoclopramide reported the greatest reduction in pain (4.7 points), followed by ketorolac (3.9 points). The participants who received valproate reported the least reduction in pain (2.8 points). A comparison of groups determined that the difference favoring metoclopramide over valproate reached statistical significance, but the difference between metoclopramide and ketorolac was not significant. The authors concluded that metoclopramide may be slightly more effective than ketorolac but could not be declared superior, and that valproate should not be used as first-line abortive therapy (Friedman et al., 2014). See Table 2 for AHS and CHS recommendations on the use of dopamine receptor antagonists.


Serotonin Receptor Agonists

The most commonly used serotonin receptor agonists include the medication class collectively known as triptans. Sumatriptan comes in various formulations such as subcutaneous, intranasal, and oral and is often used in the ED setting. Rizatriptan, eletriptan, naratriptan, almotriptan, frovatriptan, and zolmitriptan are also available in the United States, though very few nonenteral formulations are available. Other medications, such as ergots and dihidroergotamine (DHE), also affect serotonin receptors but are not used as frequently. Triptans are selective serotonin agonists, affecting only specific 5HT1B/1D receptor sites on extracerebral arteries. These medications cause vasoconstriction, inhibit vasodilator release, and inhibit the release of inflammatory mediators in the meninges. Because of the vascular effects, triptans are contraindicated in patients with uncontrolled hypertension, vascular disease, or hemiplegic migraines and should not be used if a different triptan or DHE has been administered in the past 24 hr. Because triptans affect only 5HT1B/1D receptors, the risk for serotonin syndrome is low when used concurrently with serotonin reuptake inhibitors, which target 5HT2A receptors (Kelley & Tepper, 2012a).


On the contrary, DHE is less selective than triptans and affects multiple serotonin receptors. The risk for serotonin syndrome is much higher when DHE is used concurrently with serotonin reuptake inhibitors. The most common side effects of DHE are nausea, vomiting, abdominal pain, and leg pain. The contraindications for use are similar to triptans, but DHE is also contraindicated (Category X) in pregnancy. Recent literature shows that triptans are used more frequently than DHE, and few current studies have been conducted using DHE (Kelley & Tepper, 2012a). This trend is most likely due to the improved tolerability and lower risk of serotonin syndrome with triptans.


A Cochrane review was conducted to compare various routes and dosages of sumatriptan to determine whether sumatriptan was more effective than a placebo, other triptans, or an alternative therapy such as acetaminophen/metoclopramide or aspirin/metoclopramide combinations. When sumatriptan in any formulation was compared with a placebo; pain relief was superior with sumatriptan. Subcutaneous doses were the most effective at improving reports of pain. About 50%-60% of participants were pain-free after 2 hr, compared with 13% with placebo. After 24 hr, the participants who had received sumatriptan either subcutaneously or in high oral doses were more likely to remain pain-free. However, the overall proportion of patients reporting headache freedom 24 hr later was low (17-31%), indicating a high rate of headache recurrence. All routes of sumatriptan were more effective in providing pain relief if they were administered early in the course of the migraine, while pain was still mild. The strategy of administering a second dose of sumatriptan subcutaneously if the first dose was ineffective did not have a significant effect on reports of pain. The authors concluded that sumatriptan is an effective treatment for acute migraines in adult populations when taken early in the course of a migraine and that subcutaneous dosing results in improved pain relief (Derry, Derry, & Moore, 2014).


A systematic review assessed the efficacy and safety of triptans for acute migraines compared with other common migraine therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, acetaminophen, ergots, opioids, and antiemetics. After 2 hr, 42%-76% of participants who received a triptan reported headache relief, compared with 27% for placebo. Pain freedom after 24 hr was rare with either triptans or placebo. Triptans were associated with better pain relief results than ergots. The authors concluded that triptans were more effective than placebo and ergots and equally or more effective than NSAIDs, aspirin, or acetaminophen for the treatment of acute migraine (Cameron et al., 2015).


Both the AHS and the CHS recommend the use of triptans for patients presenting to the ED with acute migraines (see Table 2). However, despite these recommendations, it is estimated that triptans are utilized in only 3%-5% of patients presenting to the ED with acute migraine (Minen et al., 2014).


There are very few studies that directly compare triptans with other parenteral medications used frequently in the ED, such as dopamine receptor antagonists. A systematic review found two RCTs that assessed the efficacy of metoclopramide intravenously compared with sumatriptan subcutaneously. In both studies, the participants were randomized to either metoclopramide 20 mg iv or sumatriptan 6 mg sc. The author concluded that both metoclopramide and sumatriptan resulted in statistically significant reduction in migraine pain in the ED setting, but the evidence to support the use of one over the other is lacking due to the small number of comparative studies (Barleycorn, 2016).


Anti-Inflammatory Drugs

Medications that suppress inflammation include NSAIDs and corticosteroids. These medications are frequently used in the ED setting to treat acute migraines. The NSAIDs inhibit the neuroinflammatory response that occurs during migraines. Cyclooxygenase COX1/COX2 inhibitors, such as ketorolac, prevent central sensitization by limiting the release of prostaglandins that activate nociceptive neurons in the trigeminovascular system. Corticosteroids suppress neuroinflammation and may reduce headache recurrence within the first 24-48 hr after acute migraine treatment (Kelley & Tepper, 2012c).


A comparative efficacy RCT studied three different medications commonly used in the ED to treat migraines to determine whether one was more effective than the others. The participants were randomized into one of three treatment groups: valproate 1 g iv, metoclopramide 10 mg iv, and ketorolac 30 mg iv. The participants who received ketorolac reported a 3.9-point pain improvement after 1 hr, compared with a 2.8-point improvement for valproate and a 4.7-point improvement for metoclopramide. Ketorolac performed better than valproate and slightly worse than metoclopramide, but the difference between ketorolac and metoclopramide did not reach statistical significance (Friedman et al., 2014).


A systematic review of eight RCTs sought to determine whether ketorolac intravenously improved pain scores and provided headache relief when compared with other medication options. Three treatment subgroups were compared: ketorolac versus meperidine, ketorolac versus intranasal sumatriptan, and ketorolac versus dopamine receptor antagonists. When ketorolac was compared with meperidine, there was no statistically significant difference in pain improvement between groups. When ketorolac was compared with intranasal sumatriptan, ketorolac was found to be significantly more effective. When ketorolac was compared with dopamine receptor antagonists, there was no statistically significant difference in pain relief. The authors concluded that ketorolac was associated with pain reduction when used to treat migraines, but it may not offer additional benefits over dopamine receptor antagonists and should be used as second-line therapy. The authors also concluded that meperidine is no more effective than ketorolac for acute migraines and should be avoided (Taggart et al., 2013).


Patients with migraine often suffer from a recurrence of the headache, despite successful initial treatment, and may return to the ED. According to a report by the Agency for Healthcare Research and Quality, a single dose of parenteral corticosteroids has been found to effectively prevent recurrence. Findings from seven RCTs assess the effectiveness of parenteral corticosteroids versus placebo for the prevention of migraine recurrence in the ED setting. Participants receiving corticosteroids were less likely to experience a recurrence of headache within 24-72 hr. The authors concluded that corticosteroids are effective in preventing recurrent migraines. There is no consensus on the best parenteral corticosteroid and dosage to use for the prevention of migraine recurrence, but the most widely studied medication is dexamethasone with a dosage range of 10-24 mg given intravenously as a single dose before ED discharge (Sumamo Schellenberg et al., 2012). The AHS has a specific recommendation supporting the use of dexamethasone for recurrence prevention but does not make a recommendation for its use as an acute abortive therapy due to insufficient evidence (Orr et al., 2016; see Table 2).



Opioid medications, such as morphine, hydromorphone, and meperidine, reduce the perception of migraine pain by affecting nociceptive input signals to the trigeminocervical complex. Opioids do not, however, affect the neurovascular and inflammatory processes that are specific to acute migraine attacks. The central sensitization pathways involved in migraines are adversely affected by opioids, and their use may result in persistent nociceptive sensitivity that prevents complete reversal of central sensitization. This process leads to persistent medication overuse headaches (Kelley & Tepper, 2012c).


An RCT sought to determine whether prochlorperazine plus diphenhydramine intravenously was more effective than hydromorphone intravenously for the management of acute migraines in the ED. The participants were randomized to two treatment groups: prochlorperazine 10 mg iv plus diphenhydramine 25 mg iv or hydromorphone 1 mg iv. After 1 hr, 51% of the participants who received hydromorphone reported no or mild pain, compared with 85% of participants who received prochlorperazine plus diphenhydramine. Sustained headache relief after 24 hr was achieved by 31% of participants who received hydromorphone, compared with 60% of participants who received prochlorperazine plus diphenhydramine. The authors determined that hydromorphone was significantly less effective than prochlorperazine plus diphenhydramine for the treatment of acute migraines (Friedman et al., 2017).


A systematic review that aimed to determine the efficacy of parenteral ketorolac, compared meperidine with ketorolac. There was not a statistically significant difference between reports of pain improvement between those receiving ketorolac and those receiving meperidine. Given the high risk of adverse outcomes related to opioid use and the availability of other effective therapies, the authors recommended against the use of meperidine for the treatment of acute migraines (Taggart et al., 2013).


The American Academy of Neurology (AAN) published a recommendation as part of the "Choosing Wisely" campaign, an initiative by the American Board of Internal Medicine that aims to promote evidence-based care. The organization discourages the use of opioid medications for migraine and reports that opioids should be used only as a last resort because more effective migraine-specific medications are available (AAN, 2013). Current opioid-prescribing guidelines published by the Centers for Disease Control and Prevention discuss the use of opioids for chronic pain conditions. The guidelines discourage the use of opioids as first-line therapy for chronic pain. Instead, nonpharmacologic therapy or nonopioid therapy should be optimized. The expected benefits should be weighed against the risk of treatment. In some instances, such as headaches, the benefits of opioid therapy are unlikely to outweigh the risks and alternative treatments should be used. When opioids are used for acute pain, the patient is at higher risk of developing long-term opioid use (Dowell, Haegerich, & Chou, 2016). Table 2 highlights the AHS and CHS recommendations for opioid use for acute migraines.


Despite the lack of evidence showing their efficacy for this indication and the overwhelming recommendations against their use, opioid medications are frequently prescribed for migraine headaches in the ED. An analysis of data from the 2010 National Hospital Ambulatory Medical Care Survey found that opioid medications are administered to 59% of patients presenting to the ED with an acute migraine (Friedman et al., 2015). A retrospective review conducted at a large academic ED found that opioids were used as initial treatment in 22.8% of all patients, and reports of pain relief were similar between those receiving migraine-specific treatments and opioids. The use of opioids as initial treatment was associated with a significantly longer ED length of stay and greater likelihood of a return ED visit within 7 days (McCarthy & Cowan, 2015).



Magnesium may improve the symptoms of a migraine through several different mechanisms. Higher levels of N-methyl-D-aspartate (NMDA) are associated with the central sensitization process of migraines, and magnesium works to block NMDA receptor sites. Magnesium also modulates the release of inflammatory mediators and nitric oxide and affects vascular tone (Kelley & Tepper, 2012a). The most common side effects of magnesium include flushing, hyporeflexia, and vasodilation-related hypotension. Magnesium should be avoided in patients with renal impairment (Food and Drug Administration, 2013).


Few studies assessing the efficacy of intravenous magnesium in the ED setting have been conducted. A meta-analysis compared intravenous magnesium with conventional analgesia or a placebo for the ED management of acute migraines in adult populations. All participants were randomized to intravenous magnesium, placebo, or a dopamine receptor antagonist. The percentage of participants who experienced a reduction in pain within 30 min was lower in the magnesium group than in the control group, but the difference did not reach statistical significance. The authors found that when magnesium was coadministered with metoclopramide, it resulted in less pain relief than when metoclopramide was administered with placebo. When magnesium was compared with placebo, it was found to be more effective for headache relief in participants who had a migraine with aura. No difference was found between magnesium and placebo in participants without a migraine aura. The authors concluded that intravenous magnesium failed to demonstrate benefits in acute pain reduction over placebo or dopamine receptor antagonists. Their findings also suggest that the combination of magnesium and metoclopramide may reduce the efficacy of metoclopramide and that magnesium may provide therapeutic benefit only when used to treat patients with migraine with aura (Choi & Parmar, 2014).


The AHS does not make a recommendation on the use of magnesium for adults presenting to the ED with an acute migraine due the uncertainty of the evidence but does acknowledge that intravenous magnesium may be beneficial to patients who present with a migraine with aura (Orr et al., 2016). See Table 2 for additional AHS and CHS recommendations on the use of magnesium.



Valproate is an anti-epileptic medication that increases levels of [gamma]-aminobutyric acid levels (GABA), which inhibits neurotransmission and decreases rapid firing of serotonergic cells in the central nervous system. It may also play a role in reducing neurogenic inflammation (Kelley & Tepper, 2012b). The use of valproate for the prevention of migraines is well documented. A Cochrane review found that valproate reduced the frequency of migraine headaches when taken regularly when compared with placebo (Linde, Mulleners, Chronicle, & McCrory, 2013). However, the use of valproate for acute migraine treatment in the ED is not well defined. Tintinalli et al. (2016) cite valproate use in the ED for acute migraines but acknowledge that it is not a validated therapy. The most current evidence addressing the use of valproate for acute migraine management reveals mixed results.


An RCT sought to assess the efficacy of intravenous valproic acid compared with sumatriptan plus metoclopramide. The participants were randomly assigned to one of two treatment groups: valproic acid 400 mg iv or sumatriptan 6 mg sc plus metoclopramide 10 mg im. The participants who received valproic acid reported a more rapid onset of pain relief compared with the sumatriptan plus metoclopramide group. After 1 hr, the patients receiving valproic acid initially reported a statistically significant reduction in pain compared with those who received sumatriptan plus metoclopramide. However, after 24 hr, there was no difference between the groups (Bakhshayesh, Saadat, Rezania, Hatamian, & Hossieninezhad, 2013).


A comparative efficacy RCT studied three medications used to treat acute migraines in the ED: valproate, metoclopramide, and ketorolac. After 1 hr, the participants in the valproate group reported the least reduction in pain. Both metoclopramide and ketorolac performed better than valproate, leading the authors to conclude that valproate should not be used as initial management for acute migraines in the ED (Friedman et al., 2014).



The use of parenteral propofol for the treatment of refractory migraines, though not recommended by either the AHS or the CHS, is currently being investigated for use. Propofol is commonly used as a general anesthetic. When used in subanesthetic doses, it is thought that propofol may affect migraine pathways by stimulating GABA receptors, ultimately reducing rapid neurotransmission of pain signals (Soleimanpour et al., 2012). Side effects of propofol include hypotension, apnea, and central nervous system depression.


An RCT sought to determine whether subanesthetic doses of propofol were as safe and effective as sumatriptan in the management of acute migraine in the ED. The participants were randomized into two treatment groups. One group received escalating doses of propofol. The other group received sumatriptan 6 mg sc. After 30 min, the participants in the propofol group had a statistically significant reduction in their pain compared with the sumatriptan group. The difference, however, was not significant after 1 and 2 hr. At 24-hr follow-up, 17.1% of the participants in the propofol group reported a recurrence of headache, compared with 55.3% in the sumatriptan group. The authors determined that propofol can be used as a rescue medication in the management of acute migraines in the ED setting (Moshtaghion et al., 2015).


A case series including eight participants aimed to evaluate the efficacy of propofol intravenously in the management of acute refractory migraines in the ED. The participants had attempted treatment with a combination of triptans, opioids, NSAIDs, or steroids but failed to achieve any headache relief after 72 hr and had presented to the ED for treatment. Propofol was administered intravenously in 10-mg boluses every 5 min until pain relief was achieved. After 30 min, the average severity of pain had reduced from 8.87 points at baseline to 1.12 points. In all cases, associated symptoms such as nausea, vomiting, photophobia, and phonophobia had resolved. After 24 hr, two of the eight participants reported a return of a mild headache and were easily managed with NSAIDs (Soleimanpour et al., 2012).



Advanced practice registered nurses (APRNs) in the ED setting need to consider several factors when determining which medication options to select for their patient with acute migraine. Patients may have already attempted NSAIDs or triptans before arrival to the ED, so these two mainstays of migraine treatment will have limited utility in the ED. Sumatriptan can be administered only twice in a 24-hr period. One review found that administering a second dose of sumatriptan subcutaneously did not result in improved pain relief (Derry et al., 2014). Triptans are most efficacious when administered early in the onset of migraine pain and patients presenting to the ED have commonly progressed to more severe pain. This leaves very few evidence-supported interventions available for these patients. The use of propofol appears to be useful for the treatment of refractory migraine, especially after multiple other treatments have failed. However, the added burdens to the ED when using propofol are numerous including the necessity of advanced monitoring equipment, extra support staff, and longer ED stays. In many practice settings, the APRNs are not allowed to administer propofol, thus further limiting the applicability of this treatment.


The potential side effects and contraindications of medications must also be considered when selecting therapy. The use of dopamine receptor antagonists may result in restlessness and akathisia. In one study, up to 8% of patients reported restlessness with metoclopramide administration (Friedman et al., 2016). Although the concurrent use of diphenhydramine reduces this risk, the resulting drowsiness and sedation may lead to decreased patient satisfaction with the treatment and longer ED stays. The antiadrenergic effects of dopamine receptor antagonists may also result in postural hypotension. Triptans are known to cause a sensation of throat or chest tightness, flushing, and dizziness that may be uncomfortable for patients. Ketorolac, even when used short term, can cause acute kidney injuries and increase the risk of gastrointestinal bleeding. Corticosteroids may cause adrenal and immune suppression, but these effects are more likely to occur with long-term use. Opioid use can result in respiratory depression, sedation, and increased risk of dependency (Kelley & Tepper, 2012a-c). The APRN in the ED must discuss the risks and benefits of various treatment options with patients and set mutually agreed-upon goals for treatment.


Despite the evidence supporting several pharmacologic therapies for migraine management in the ED, many patients experience a relapse of migraine headache within 24-72 hr of treatment. Of the studies reviewed, only about 30% of participants experienced complete headache resolution after 24 hr. The lack of prolonged efficacy of the available therapeutic options is cause for concern, as sustained headache freedom is an important component of treatment (Rowe & Richer, 2015). The administration of parenteral corticosteroids in conjunction with other abortive treatments appears to reduce migraine recurrence rates and should be considered for use (Sumamo Schellenberg et al., 2012). Future studies are needed to find new or alternative medications that result in sustained headache freedom.



Current evidence and migraine management guidelines support the use of dopamine receptor antagonists, NSAIDs, and serotonin receptor agonists for the management of acute migraines in the ED. The evidence also suggests that opioid medications should be avoided. Magnesium may be useful for patients presenting with a migraine with aura. Corticosteroids may be beneficial in reducing migraine relapse headaches. There is less robust evidence regarding the use of valproate or propofol with no clear determination about the efficacy of these therapeutic options.




American Academy of Neurology. (2013). Choosing wisely: Five things physicians and patients should question. Retrieved from[Context Link]


Bakhshayesh B., Saadat S. M. S., Rezania K., Hatamian H., Hossieninezhad M. (2013). A randomized open-label study of sodium valproate vs sumatriptan and metoclopramide for prolonged migraine headache. The American Journal of Emergency Medicine, 31(3), 540-544. doi:10.1016/j.ajem.2012.10.014. Retrieved from[Context Link]


Barleycorn D. (2016). Systematic review: Is metoclopramide more effective than sumatriptan in relieving pain from migraine in adults in the emergency department (ED) setting? International Emergency Nursing, 27, 51-55. doi:10.1016/j.ienj.2016.02.004 [Context Link]


Cameron C., Kelly S., Hsieh S. C., Murphy M., Chen L., Kotb A., Wells G. (2015). Triptans in the acute treatment of migraine: A systematic review and network meta-analysis. Headache, 55(Suppl. 4), 221-235. doi:10.1111/head.12601 [Context Link]


Choi H., Parmar N. (2014). The use of intravenous magnesium sulphate for acute migraine: Meta-analysis of randomized controlled trials. European Journal of Emergency Medicine: Official Journal of the European Society for Emergency Medicine, 21(1), 2-9. doi:10.1097/MEJ.0b013e3283646e1b [Context Link]


Derry C. J., Derry S., Moore R. A. (2014). Sumatriptan (all routes of administration) for acute migraine attacks in adults-overview of Cochrane reviews. The Cochrane Database of Systematic Reviews, (5):CD009108. doi:10.1002/14651858.CD009108.pub2 [Context Link]


Dowell D., Haegerich T. M., Chou R. (2016). CDC guideline for prescribing opioids for chronic pain-United States, 2016. MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report. Recommendations and Reports/Centers for Disease Control and Prevention, 65(1), 1. Retrieved from[Context Link]


Edlow J. A., Panagos P. D., Godwin S. A., Thomas T. L., Decker W. W. (2008). Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with acute headache. Annals of Emergency Medicine, 52(4), 407-436. doi:10.1016/j.annemergmed.2008.07.001 [Context Link]


Evers S., Afra J., Frese A., Goadsby P. J., Linde M., May A., Sandor P. S. (2009). EFNS guideline on the drug treatment of migraine-revised report of an EFNS task force. European Journal of Neurology, 16(9), 968-981. doi:10.1111/j.1468-1331.2009.02748.x [Context Link]


Food and Drug Administration. (2013). Magnesium sulfate. Retrieved from[Context Link]


Friedman B. W., Cabral L., Adewunmi V., Solorzano C., Esses D., Bijur P. E., Gallagher E. J. (2016). Diphenhydramine as adjuvant therapy for acute migraine: An emergency department-based randomized clinical trial. Annals of Emergency Medicine, 67(1), 39.e3. doi:10.1016/j.annemergmed.2015.07.495 [Context Link]


Friedman B. W., Garber L., Yoon A., Solorzano C., Wollowitz A., Esses D., Gallagher E. J. (2014). Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine. Neurology, 82(11), 976-983. doi:10.1212/WNL.0000000000000223 [Context Link]


Friedman B. W., Irizarry E., Soloranzo C., Latev A., Rosa K., Zias E., Gallagher J. E. (2017). Randomized study of IV prochlorperazine plus diphenhydramine vs hydromorphone for migraine. Neurology, 89(20), 2075-2082. [Context Link]


Friedman B. W., West J., Vinson D. R., Minen M. T., Restivo A., Gallagher E. J. (2015). Current management of migraine in US emergency departments: An analysis of the National Hospital Ambulatory Medical Care Survey. Cephalalgia: An International Journal of Headache, 35(4), 301-309. doi:10.1177/0333102414539055 [Context Link]


Gaffigan M. E., Bruner D. I., Wason C., Pritchard A., Frumkin K. (2015). A randomized controlled trial of intravenous haloperidol vs. intravenous metoclopramide for acute migraine therapy in the emergency department. The Journal of Emergency Medicine, 49(3), 326-334. doi:10.1016/j.jemermed.2015.03.023 [Context Link]


Headache Classification Committee of the International Headache Society (IHS). (2013). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia: An International Journal of Headache, 33(9), 629-808. doi:10.1177/0333102413485658 [Context Link]


Kelley N. E., Tepper D. E. (2012a). Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium. Headache, 52(1), 114-128. doi:10.1111/j.1526-4610.2011.02062.x [Context Link]


Kelley N. E., Tepper D. E. (2012b). Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. Headache, 52(2), 292-306. doi:10.1111/j.1526-4610.2011.02070.x [Context Link]


Kelley N. E., Tepper D. E. (2012c). Rescue therapy for acute migraine, part 3: opioids, NSAIDs, steroids, and post-discharge medications. Headache, 52(3), 467-482. doi:10.1111/j.1526-4610.2012.02097.x [Context Link]


Levin M. (2015). Approach to the workup and management of headache in the emergency department and inpatient settings. Seminars in Neurology, 35(6), 667-674. doi:10.1055/s-0035-1564300 [Context Link]


Linde M., Mulleners W. M., Chronicle E. P., McCrory D. C. (2013). Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. The Cochrane Database of Systematic Reviews, 6, CD010611. doi:10.1002/14651858.CD010611 [Context Link]


Marmura M. J., Silberstein S. D., Schwedt T. J. (2015). The acute treatment of migraine in adults: The American Headache Society evidence assessment of migraine pharmacotherapies. Headache: The Journal of Head and Face Pain, 55(1), 3-20. doi:10.1111/head.12499 [Context Link]


McCarthy L. H., Cowan R. P. (2015). Comparison of parenteral treatments of acute primary headache in a large academic emergency department cohort. Cephalalgia: An International Journal of Headache, 35(9), 807-815. doi:10.1177/0333102414557703 [Context Link]


Minen M. T., Tanev K., Friedman B. W. (2014). Evaluation and treatment of migraine in the emergency department: A review. Headache, 54(7), 1131-1145. doi:10.1111/head.12399 [Context Link]


Moshtaghion H., Heiranizadeh N., Rahimdel A., Esmaeili A., Hashemian H., Hekmatimoghaddam S. (2015). The efficacy of propofol vs. subcutaneous sumatriptan for treatment of acute migraine headaches in the emergency department: A double-blinded clinical trial. Pain Practice: The Official Journal of World Institute of Pain, 15(8), 701-705. doi:10.1111/papr.12230 [Context Link]


Orr S. L., Aube M., Becker W. J., Davenport W. J., Dilli E., Dodick D., Christie S. N. (2015). Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings. Cephalgia, 35(3), 271-284. doi:10.1177/0333102414535997 [Context Link]


Orr S. L., Friedman B. W., Christie S., Minen M. T., Bamford C., Kelley N. E., Tepper D. (2016). Management of adults with acute migraine in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies. Headache: The Journal of Head and Face Pain, 56(6), 911-940. doi:10.1111/head.12835 [Context Link]


Rowe B. H., Richer L. (2015). Improving migraine headache management in emergency departments: The time has come. Cephalalgia, 35(4), 289-290. doi:10.1177/0333102414539056 [Context Link]


Silberstein S. D., Holland S., Freitag F., Dodick D. W., Argoff C., Ashman E. (2012). Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults: Report of the quality standards subcommittee of the American academy of neurology and the American Headache Society. Neurology, 78(17), 1337. [Context Link]


Soleimanpour H., Taheraghdam A., Ghafouri R., Taghizadieh A., Marjany K., Soleimanpour M. (2012). Improvement of refractory migraine head-ache by propofol: Case series. International Journal of Emergency Medicine, 5(1), 1-4. doi:10.1186/1865-1380-5-19 [Context Link]


Sumamo Schellenberg E., Dryden D. M., Pasichnyk D., Ha C., Vandermeer B., Friedman B. W., Rowe B. H. (2012). Comparative effectiveness review no. 84 acute migraine treatment in emergency settings. Rockville, MD: Agency for Healthcare Research and Quality. [Context Link]


Taggart E., Doran S., Kokotillo A., Campbell S., Villa-Roel C., Rowe B. H. (2013). Ketorolac in the treatment of acute migraine: A systematic review. Headache, 53(2), 277-287. doi:10.1111/head.12009 [Context Link]


Tintinalli J. E., Stapczynski J. S., Ma O. J., Yealy D. M., Meckler G. D., Cline D. (2016). Tintinalli's emergency medicine (8th ed.). New York, NY: McGraw-Hill Education. [Context Link]


Zitek T., Gates M., Pitotti C., Bartlett A., Patel J., Rahbar A., Clark J. M. (2017). A comparison of headache treatment in the emergency department: Prochlorperazine versus ketamine. Annals of Emergency Medicine, 71(3), 369-377.e1. doi:10.1016/j.annemergmed.2017.08.063 [Context Link]


acute migraine; emergency department; headaches; pharmacotherapy