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Sumamo Schellenberg E, Dryden DM, Pasichnyk D, et al. Acute Migraine Treatment in Emergency Settings [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Nov. (Comparative Effectiveness Reviews, No. 84.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Acute Migraine Treatment in Emergency Settings

Acute Migraine Treatment in Emergency Settings [Internet].

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Migraine is a chronic neurovascular disorder characterized by dysfunction of central and peripheral nociceptive pathways and intracranial vasculature.1 Migraine is characterized by a moderate to severe, recurrent, unilateral or bilateral, throbbing headache that can last hours to days. It may be accompanied by nausea, vomiting, and sensitivity to light, sound, touch, and/or smell. Approximately 25 percent of people with migraine experience transient visual disturbance, motor symptoms, or language disturbance.1,2 The triggers of migraine headaches are multi-factorial, and the pathophysiology is complex and incompletely understood. Current research suggests that migraines occur as a result of a cascade of events involving activation of the trigeminovasucalar system, cortical spreading depression, and neuronal sensitization.3 Ongoing research in migraine genetics indicates that there may be a genetic disposition to migraine.4

Migraine affects 12 percent of the general population in the United States.5 Acute exacerbations of episodic and chronic migraine cause severe and disabling pain that may result in visits to an emergency department (ED) as well as decreased productivity and missed time from work, school, and other activities.6 In the United States, migraine and related medical issues result in costs of more than $13 billion per year due to lost productivity.7 In Canada, this annual cost has been estimated at $3,025 per patient due to medical and indirect costs.8

Migraine has a negative impact on overall quality of life.9 It is associated with psychiatric and medical comorbidities including major depressive disorder, bipolar disorder, anxiety and social phobias, cardiovascular risk,10 and stroke.11 Inadequate care of migraine is common: only 56 percent of migraine patients have been diagnosed correctly, and 49 percent use only over-the-counter rather than prescription medications to treat their headache.5

Diagnosis and Treatment

Migraine Headaches

Headaches result from a variety of causes, some of which are benign and self-limiting while others are more serious. Once secondary causes of headache are excluded, migraine can be classified using criteria established by the International Headache Society.2 Migraines come in several types; some are more common than others. A migraine headache preceded by an aura (e.g., a set of self-limited sensory [visual, tactile, and/or olfactory] symptoms) is referred to as a classic migraine. Headaches not preceded by an aura are referred to as common migraines. A diagnosis of migraine headache can be made when the search for all malignant causes of headache has been exhausted and the patient meets the following criteria for migraine headache:

  • Recurrent (≥5 attacks in lifetime)
  • Prolonged (lasting 4–72 hours)
  • Associated with ≥2 of the following:
    • Unilateral location, pulsating quality
    • Moderate or severe pain intensity
    • Aggravated by or causing avoidance of routine physical activity
  • Associated with >1 of the following:
    • Nausea
    • Vomiting
    • Photophobia + Phonophobia/sonophonia

In contrast, chronic migraine is a specific type of migraine headache; it is defined as headache on >15 days per month for at least 3 months.2

Acute Exacerbations and Emergency Department Presentation

Migraine causes acute headaches, which typically last 4 hours to 3 days if untreated and which frequently require bed rest, pain medications, and time off from work and other activities. Although most patients with migraine function normally between attacks, for many, migraine is a pervasive disorder that interferes with work, family, and social life.1 Most individuals with migraine are able to treat their attacks at home; however, this treatment is not always successful. Of Americans with migraine, seven percent reported using an ED or urgent care center for treatment of severe headache within the previous 12 months.12 In the United States, headaches accounted for 2.2 percent of visits or 2.1 million ED visits per year.13 Of patients who use an ED for treatment of migraine, 19 percent make multiple visits over the course of 1 year.14

While headache is a common cause of presentation to the ED, there is substantial practice variability among emergency clinicians in North America.1518 Twenty disparate parenteral agents are used to treat acute migraine in EDs in the United States.15 There is substantial variability across EDs. For example, dopamine antagonists are used in 60 percent of visits in some EDs compared with only 20 percent of visits in others.17 Moreover, over-use of opioids has been observed in several studies.15,16 Overall, there is a considerable gap between what is practiced in EDs and the evidence-based medical care, suggesting that a synthesis of this literature could lead to more standardized care.

Acute Migraine Management

Acute Headache Pain and Symptoms

Many agents are used to treat acute migraine, including 5-hydroxytryptamine (HT) receptor agonists (e.g., triptans), dopamine receptor antagonists (e.g., phenothiazines, metoclopramide, droperidol), ergot derivatives (e.g., dihydroergotamine [DHE]), intravenous (IV) nonsteroidal anti-inflammatory agents (NSAIDs), and opioids. While earlier studies have shown that opioids are commonly used,15,16 the most common first line agents used for migraine treatment in more recent studies include metoclopramide and prochlorperazine, which is a phenothiazine.1921 While alternative phenothiazines exist, prochlorperazine is usually preferred due to its efficacy and safety.22,23 IV DHE and ketorolac are also used to treat acute migraine. Opioids are often used to treat acute migraine despite their recognized ability to cause dependence and their association with a higher risk of headache relapse.14 A number of selective 5-HT1 receptor agonists have been developed and represent a class of drugs called triptans. These agents are indicated for the acute treatment of migraine in adults; however, their use in many EDs is limited due to reduced efficacy with delayed administration,24 the need for cardiac risk stratification prior to administration,25 and frequent adverse events.26 Finally, some physicians use agents sequentially (e.g., metoclopramide followed by ketorolac, if not fully recovered following in a 30–60 minute assessment period); however, the use of a combination treatment is also used (e.g., metoclopramide and ketorolac at the same time).21 Table 1 summarizes pharmacological interventions that have been approved by the U.S. Food and Drug Administration and that are used, often off-label, for acute migraine.

Table 1. Summary of pharmacological interventions for acute migraine.

Table 1

Summary of pharmacological interventions for acute migraine.

The first objective of this comparative effectiveness review (CER) was to assess the effectiveness of various parenteral medications on pain relief and relapses for adult patients with acute migraine who come to an ED for treatment.

Side Effects

The second objective of this CER was to assess important immediate and short-term side effects of the different interventions. For example, opioids may be associated with drowsiness and impaired ability to function. Metoclopramide and the phenothiazines may cause akathisia and extrapyramidal side effects. This CER examined the adverse effects caused by parenteral migraine therapies.

Prevention of Recurrence

Some patients with migraine suffer a short-term recurrence of headache after successful initial treatment that results in a return visit to a physician or ED. Research has shown that short-term or single-dose systemic corticosteroids, delivered intravenously (e.g., dexamethasone) or orally27 prevent headache recurrence after treatment in an ED for acute migraine.28 These agents are infrequently used,29 however, and have important long-term side effects.28 A third focus of this CER was to examine the benefit and risk of using corticosteroids for preventing recurrence of acute migraine.

Scope and Key Questions

The objective of this report was to synthesize the available evidence on the comparative effectiveness of parenteral pharmacological interventions in the treatment of migraine and in the prevention of migraine relapse. The rationale for focusing on parenteral interventions is threefold: (1) the majority of patients presenting to the ED have already failed oral medications and other home remedies; (2) most patients presenting to the ED are experiencing nausea and/or vomiting so continued oral interventions can prove to be futile; (3) the rapid onset and efficacy of parenteral agents is appealing to both patients and clinicians. The Key Questions (KQs) are as follows:

Key Question 1

What is the comparative effectiveness of parenteral pharmacological interventions versus standard care, placebo, or an active treatment in the treatment of acute migraine headaches in adults visiting the ED?

Key Question 2

What is the comparative effectiveness of adding parenteral or oral corticosteroids versus adding placebo to acute parenteral pharmacological interventions to prevent recurrence of acute migraine headaches in adults after being treated in the ED?

Key Question 3

What are the associated short-term adverse effects of these parenteral pharmacological interventions, and do they differ across interventions?

Key Question 4

Does the development of adverse events (especially akathisia) differ following the administration of anticholinergic agents and phenothiazines when compared with anticholinergic agents and metoclopramide?

Key Question 5

Does the effectiveness and safety of the parenteral pharmacological interventions vary in different subgroups, including sex, race, duration of headaches, and non-responders while in the ED?

Key Question 6

Does the effectiveness and safety of adding parenteral or oral corticosteroids to acute parenteral pharmacological interventions vary in different subgroups, including sex, race, duration of headaches, and non-responders?

Figure 1 provides an analytic framework to illustrate the population (P), interventions (I), control/comparison (C), and outcomes (O) that guided the literature search and synthesis. This figure depicts the KQs within the context of the PICOTS (population, intervention, comparator, outcomes, timing of outcome measurement, and setting). In general, the figure illustrates how parenteral pharmacological interventions and parenteral or oral corticosteroid interventions versus standard care, placebo, or an active comparator may result in intermediate outcomes such as time in ED, recurrence of severe symptoms, or return ED visits within 24–48 hours, and in final outcomes such as pain relief, satisfaction with experience, quality of life, and return to activities. Adverse effects may occur at any point after the treatment was received and were assessed up to 3 months post-intervention.

Figure 1 is the analytic framework for acute migraine treatments in emergency settings. The flow diagram begins on the left side and outlines how adults presenting to the emergency department or an equivalent setting can be treated with parenteral pharmacological interventions to treat migraine or parenteral or oral corticosteroids to prevent recurrence of acute migraine after discharge from the emergency department. The intermediate outcomes include time in emergency department, vital signs, and recurrence of severe symptoms/return visits to the emergency department within 24–48 hours. Final health outcomes, which are measured up to 7 days after the emergency department visit include pain relief, satisfaction with experience, recurrence of migraine headache, and quality of life or return to activities. The flow diagram also shows that adverse effects of treatment up to 3 months postintervention will be recorded.

Figure 1

Analytic framework. KQ = Key Question; ED = emergency department


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