Reducing migraine return with corticosteroids: An extra chance to improve migraine care

Migraine treatment in the emergency department is a scenario patient and physician alike would prefer to avoid. With severe pain, aversion to light and sound, nausea, vomiting, and a desire to achieve sleep, a migraine sufferer would naturally choose less provocative surroundings, if only relief could be had elsewhere. For her emergency physician, the patient with migraine almost never has a life-threatening, but a life-interrupting, episode, one that lasts hours to days and responds inconsistently to interventions. Then, at discharge, after success and relief appear together, the question looms for both patient and physician, will the migraine return?

Just as the most common rank of a graduating class (minimum size one) is valedictorian, any given visit to an emergency department for headache is most likely be the first, but it is repeated visits, repetitive, treatment-resistant migraine attacks, that raise the signal that a migraine sufferer is not managing well. One possible tool to delay headache recurrence after a prolonged migraine attack is the class of corticosteroids (denoting any naturally occurring or analog glucocorticoid or mineralocorticoid). In their systematic review in the current issue of Cephalalgia, Woldeamanuel and co-authors (1) searched the entirety of accessible medical literature from the time of production of synthetic corticosteroids to the present to identify relevant data about a common pharmacological treatment of migraine in emergency departments and similar settings. The authors used multiple search strategies of published and unpublished sources, evaluated study quality, and abstracted information to allow for meta-analysis using current methods. The report of this exhaustive search should be of interest to headache physicians because it contains both encouraging and discouraging news.

In 60 years’ data, only 25 studies appear to address this clinical scenario, corticosteroid treatment of migraine attack in acute care settings. For the reader’s convenience and further study, these 25 studies are summarized by the authors in Table 1 (1). The identified studies’ sum is greater than the parts; for example, although the conclusion of one individual study (2) was negative in a primary outcome, the secondary outcome in a subset of patients was positive, and leads to classification under ‘favorable outcomes’ for the treatment (1 (Table 1)). The data sets retrieved and reviewed point in the same direction: For the migraine attack that resists other therapy, corticosteroids (most often a single dose of 10 mg intravenous dexamethasone, Figure 5 (1)) tend to reduce the recurrence rate and severity of subsequent headaches. Opportunities to expand reviewable data abound: The number of patients for whom data have been captured for this systematic review and analysis (just under 4000) must be a figure many orders of magnitude lower than those exposed over six decades to treatment outside of experimental settings. The conclusion based on available data is promising: Short-term, high-dose corticosteroid use now justifiably retains its “time-honoured place” (3) in the toolkit for the treatment of prolonged migraine attacks—the accumulation of evidence supports current practice. Some of the studies identified may not be widely generalizable because of the adjuvant role of the corticosteroid, with primary treatments that may not be applied in all or most cases (e.g. metoclopramide and diphenhydramine in Friedman et al. (4)). Discouraging for patients and clinicians seeking all the answers today, but encouraging for those keen to tackle today’s questions, such limitations show the work to be done: Increasing the number of attack-and-treatment pairs studied, improving reporting and accessibility of data, and comparing routes and particular agents head-to-head would refine subsequent recommendations regarding corticosteroids. The question of route is especially important as it often defines the treatment setting: If parenteral treatments are required, their delivery is likely to remain in an acute-care setting; if enteral treatments are equally effective and adequately tolerated by the gut, they may be prescribed in advance and used by the patient in more comfortable surroundings.

Between acute abortive migraine therapy (for which evidence suggests that intravenous dexamethasone is not superior to placebo (5)) and preventive migraine therapy (for which corticosteroids have not been extensively used, studied or yet led to accessible results (namely, registered study NCT00915473, examining methylprednisolone injection via greater occipital nerve block, and NCT01813591, on adrenocorticotropic hormone injection) (6,7)), rescue therapy for migraine with the goal of reducing future short-term recurrence may include a corticosteroid. The fact that a particular intervention (corticosteroid) may be effective as a rescue therapy but not as an acute abortive therapy or prophylactic suggests that the underlying pathophysiology differs, or that the effects of the intervention are specific to the time frame of the condition. The authors suggest the latter, noting the long biologic half-life of dexamethasone, for example (1). The authors suggest elsewhere that short, tapering doses of corticosteroids may be used safely six times annually, based on expert recommendations (8). Knowing that the absolute risk reduction falls rapidly from one day to three days post-headache ((1) Figure 3a) and that the number needed to treat to avoid recurrence at 72 hours is 10 ((1) Figure 3b), with a treatment with course limits on repetition for any individual patient, the risks (however small) and benefits need to be considered. The benefit accounting for dexamethasone, for example, should include low cost and near-universal availability (found on the World Health Organization (WHO) Model Lists of Essential Medicines (9)), but it still must be serve a purpose.

The key to justifying the use of a medication that may not be especially helpful acutely or long term is that it is one that buys time in between. (This time comes at the expense of hopefully small risks, the data suggest.) In the days after discharge from an acute care facility with corticosteroid (among other treatments) for prolonged and therapy-resistant migraine attack, the patient needs continuing care. This care should include review of any modifiable factors leading to the index attack, a re-assessment of the efficacy and availability of acute abortive therapies, a re-evaluation, or strong consideration, of prophylactic therapy, documentation as to the results of the emergency interventions provided, and adjustment of future rescue plans accordingly. The sort of care recommended here and by the authors (1) would be expected of a headache specialist or headache clinic. Those who focus clinically on patients with migraine should aim to define and promote adequate tools for patients at all stages in this chronic disease with episodic manifestations: preventively, acutely, in-need of rescue, and, in a window enlarged by judicious corticosteroid use, the authors successfully argue, post-rescue. The best care of migraine attacks leading to emergency care may now include delaying the recurrence of the next attack to allow for transfer of care (during remission) to the headache specialist.