Aspirin Key to Expanding Access to Effective Migraine Treatment?

Damian McNamara

December 10, 2019

Aspirin is an effective option for acute treatment and prevention of recurrent migraine attacks, particularly among patients who can't tolerate or afford newer, much more expensive medications, new research suggests.

A review of randomized trials suggests that high-dose aspirin is effective and safe for acute migraine and that low-dose aspirin may help prevent migraine attacks.

"The take-home message is that most headache disorders are treated by primary care providers and that many patients have no health insurance or high co-pays, so that the prescription drugs of proven benefit may neither be available or affordable," senior author Charles H. Hennekens, MD, DrPH, Florida Atlantic University in Boca Raton, told Medscape Medical News.

"We have provided a review of the randomized evidence that suggests that aspirin may be something [physicians] wish to consider in their patients ― high doses for treatment, low doses for prevention of recurrent attacks," added Hennekens.

The study was published online October 12 in the American Journal of Medicine.

Prevalent, Disabling

Migraine affects an estimated 14% of the general population and is more prevalent in women (18%) than men (9%). About 90% of migraine patients report moderate to severe pain associated with their attacks. More than 50% report severe impairment, which often results in reduced work and school productivity.

Migraine treatment and prevention options include prescription medications with proven efficacy. However, these medications are expensive, and access may be limited for patients without health insurance or who have high co-pays. Estimates show that rates of those who are uninsured or underinsured are 8.5% nationwide and 13% in Florida.

In addition, for all migraine patients, these medications may be either poorly tolerated or contraindicated, the investigators note.

To assess the safety and efficacy of aspirin in migraine treatment and prevention, the researchers examined the evidence from randomized controlled trials of high- and low-dose aspirin.

They assessed randomized trials and meta-analyses in which participants received 900 mg to 1200 mg of aspirin for acute migraine or 81 mg to 325 mg daily for prevention of recurrence.

High-dose aspirin was more effective than placebo in multiple trials that examined relief of acute migraine attacks, the researchers note. In addition, efficacy was comparable to other medications, including 400-mg ibuprofen or 50-mg sumatriptan.

Although the evidence also indicates that migraine relief is comparable for 900- to 1200-mg aspirin and 100-mg sumatriptan, the researchers note that sumatriptan provides faster relief.

In addition, compared to prescription migraine treatments, aspirin can provide "an added advantage of decreasing the frequently concomitant symptoms of nausea, photophobia, and phonophobia," the researchers note.

"Cost Must Be Considered"

High-dose aspirin is sometimes combined with metoclopramide for acute migraine. The review showed that metoclopramide, which is typically used to mitigate gastrointestinal (GI) problems, can increase the benefit of aspirin for relief of migraine pain and associated symptoms such as nausea.

However, metoclopramide comes with a US Food and Drug Administration (FDA) black box warning advising against long-term use (more than 12 weeks), which is associated with an increased risk of developing tardive dyskinesia.

"The totality of evidence, which includes data from randomized trials, suggests that high-dose aspirin, in doses from 900 to 1300 milligrams, given at the onset of symptoms, is an effective and safe treatment option for acute migraine headaches," the researchers state.

Overall, according to some, but not all, randomized trials in the review, 81 mg to 325 milligrams aspirin daily "may be an effective and safe treatment option for the prevention of recurrent migraine headaches," the researchers write.

Beta blockers, antiepileptic agents, and botulinum toxin also have proven efficacy for prevention of recurrent migraines, the investigators add.

The newest class of migraine medications, including monoclonal antibodies such as erenumab and galcanezumab, "do not abolish the occurrence of acute migraines but seem to decrease their frequency, severity, and duration."

However, the researchers add that owing to their high costs, erenumab and other monoclonal antibodies will likely be reserved for migraine sufferers for whom other first-line medications fail.

Aspirin's relatively favorable side effect profile and extremely low cost are good reasons to consider prescribing aspirin so as to increase access to migraine therapy.

However, although effective, Hennekens said he would not recommend that physicians whose migraine patients are doing well with other therapies switch to aspirin.

"I would be the last person to say they should abandon something that is working well," he said.

"In today's healthcare system, benefits and risks should be the primary consideration ― but for better or worse, cost has also got to be considered," he said.

Hennekens added that future trials include aspirin as "a safe, effective, and less costly comparative drug."

Simple, Straightforward

In an accompanying editorial, Joseph S. Alpert, MD, Department of Medicine, University of Arizona, Tucson, describes the study as a "thoughtful and carefully researched review of high-dose aspirin therapy for migraine headache.

"Their findings are simple and straightforward," he adds. High-dose aspirin was "shown to be effective in many migraine patients when compared with alternative more expensive therapies.

"Since aspirin is readily available without a prescription in the US, it certainly seems like something that should be tried in migraine sufferers before physicians prescribe more complex, expensive, and hence less available medications," writes Alpert, who is also editor-in-chief of the American Journal of Medicine.

However, he adds, clinicians should also consider the potential drawbacks of high-dose aspirin therapy, including GI bleeding and peptic ulcer disease. Taking aspirin with food or in combination with proton pump inhibitor therapy could help alleviate potential GI side effects, Alpert notes.

"[P]hysicians should always try this simple and inexpensive high-dose aspirin regimen as the initial therapeutic attempt for migraine headache control. If aspirin works to abort or ameliorate the headaches, then it should be tried as a prophylactic measure to see if it can prevent the occurrence of these debilitating headaches," he writes.

"Hopefully, this would lead to less disability and loss of employment time for these patients who are so common in the US and throughout the world."

"Textbook Knowledge"

Commenting on the study for Medscape Medical News, Peter Goadsby, MD, PhD, a neurologist and headache specialist at the University of California, San Francisco, said the use of aspirin for the acute treatment of migraine is "textbook knowledge."

"It's nice to put together the evidence, but I am not sure who the audience is...for what is simply medical school knowledge," Goadsby said.

"There is no reason to think aspirin will be useful in patients not suitable or failing newer medicines since it would be exceptional to see a patient who can tolerate aspirin who has not used it long before they see neurologists ― or, indeed, GPs," he added.

Hennekens is an advisor for Amgen, the British Heart Foundation, Cadila, the Canadian Institutes of Health Research, DalCor, Regeneron, the Wellcome Foundation, the FDA, and UpToDate. Alpert and Goadsby have disclosed no relevant financial relationships.

Am J Med. Published online October 12, 2019. Abstract, Editorial

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