Migraine is a common neurological condition and one of the largest causes of disabilities worldwide. Despite this, the condition is both underdiagnosed and undertreated. Over 90% of people who suffer from migraine report moderate to severe pain, with 1% to 5% of individuals experiencing recurring migraines. Over 50% of this population report severe impairment, reduced work or school productivity, and/or the need for bed rest.1 Additionally, research indicates a higher prevalence of migraine reported in women compared to men.2

Several medications are prescribed for the treatment of migraines, each with varying levels of efficacy. Some of the most common medications include angiotensin-converting enzyme inhibitors, antiseizure drugs, beta-blockers, calcium blockers, antidepressants, and nonsteroidal anti-inflammatory drugs (NSAIDs). Despite their effectiveness, many of these drugs may not be readily available, are poorly tolerated, or are contraindicated. Indeed, there is growing evidence supporting the fact that many US patients are inadequately treated for migraines due to the high cost of medications, as well as limited access to health care.1

In one systematic review, study researchers found migraines to be particularly common and burdensome for historically disadvantaged segments of the population.3 This is a noteworthy observation since treatments for migraines are rapidly improving and becoming more targeted and personalized – and therefore more expensive and inaccessible for these segments.


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Could aspirin offer a solution? Current evidence has demonstrated the effectiveness of aspirin as an over-the-counter treatment for acute migraines with the added appeal of safety, low cost, and a relatively favorable side effect profile. Additionally, aspirin has not only been effective as a treatment for current migraine; it has also demonstrated prophylactic (preventative) properties.

High-dose aspirin for the treatment of acute migraine

Research indicated that aspirin was effective for acute migraines both as a solitary modality and in combination with other drugs.4 Aspirin functions to irreversibly inhibit cyclooxygenase enzymes (COX-1 and COX-2), which results in decreased prostaglandin synthesis and a reduction in pain and inflammation.5 Studies to date have confirmed the beneficial effects of aspirin on migraine without aura, but its effects on migraine with aura are unclear and require further investigation.6

Research on the effectiveness of aspirin in the treatment of migraine alone or in combination with other drugs is ongoing. Metoclopramide is an antiemetic that is often prescribed alongside high-dose aspirin to treat acute migraine. A meta-analysis of 13 randomized control trials (RCTs) comparing 1,000mg of aspirin (with and without 10mg of metoclopramide) to placebo or sumatriptan (Imitrex; 50mg or 100mg), found no significant differences between aspirin and 50mg or 100mg of sumatriptan doses when assessing reduced head pain or complete remission of pain.7

A study assessing the effects of aspirin alone found that, when administered between the ranges of 900 mg to 1000mg, aspirin was effective in providing relief at 2 hours for between 48% and 52% of participants, compared with between 19% and 34% in the placebo group. 8 An RCT of 433 patients demonstrated that 1000mg of aspirin produced similar benefits when compared to 50mg of sumatriptan.9 This was further supported by recent research concluding that high-dose aspirin administered between the ranges of 900mg to 1300mg was effective in patients with migraines when compared with alternative, more expensive therapies such as beta-blockers or antiseizure drugs.1

Many of these studies also reported a decrease in the frequently concomitant symptoms of nausea, photophobia, and phonophobia in patients receiving 900mg to 1300mg of aspirin.1 Furthermore, randomized evidence on the side effects of aspirin showed promising results in comparison to both traditional, nonselective NSAIDs, and cyclooxygenase-2 inhibitors.10

The role of aspirin in migraine prophylaxis

Recurring or chronic migraines are those that occur for more than 15 days per month, and the leading cause of suffering and disability at the national and global level. It has been estimated that more than 25% of these patients are candidates for prophylactic therapies, yet remain untreated.3

Several medications prescribed for the prevention of chronic migraine, such as tricyclic antidepressants, anticonvulsants, and beta-blockers are effective – however, they have significant side effects that result in poor medication adherence and other health complications. Newer biologics have also demonstrated efficacy, but their benefit-to-risk ratios are still being assessed in ongoing randomized trials.1

In a systematic review comprising 8 studies with over 28,326 participants, findings indicated positive outcomes for the role of aspirin in the prevention of migraines.11 The study authors found that doses at least 325mg per day lead to a significant reduction in the frequency of migraine in most studies.

In a clinical trial exploring the effectiveness of aspirin administered in combination with the antiplatelet medication, Clopidogrel (Plavix), there was a significant decrease in the occurrence of new onset migraines within 3 months of patients receiving a coronary artery stent. 12

A case for the underuse of aspirin in the US

An article in the Journal of Family Practice suggested that physicians are unlikely to recommend aspirin for the treatment of migraines despite growing evidence supporting its effectiveness. The authors speculated that a possible reason is that “patients often expect a prescription” for their migraine headaches. They go on to say that, “… [patients] may feel shortchanged if they’re told to take an aspirin. Providing a prescription for the antiemetic metoclopramide, as well as a brief explanation of the evidence indicating that aspirin is effective for migraine, may adequately address such expectations.”13 They agree that the benefits of aspirin for the treatment of migraine “might not be getting the traction it deserves.”

Future prospects for the treatment of chronic migraines include a nonpharmacologic approach in the form of electronic aspirin.14 This is a patient-powered tool that involves the permanent implant of a nerve-stimulating device in the upper gum. The pointed tip of the implant connects with a nerve bundle that is associated with migraines, and during the onset of the pain, is activated using a hand-held remote. The stimulation of the nerve bundle is reported to block the pain-causing neurotransmitters and provides pain relief. It is expected that the demand for electronic aspirin devices will reach 220,000 units by 2025, with the hospital segment likely to be the major end user for the device.

References

1. Biglione B, Gitin A, Gorelick PB, Hennekens C. Aspirin in the treatment and prevention of migraine headaches: Possible additional clinical options for primary healthcare providers. Am J Med. 2020;133(4):412-416. doi:10.1016/j.amjmed.2019.10.023

2. Lay CL, Broner SW. Migraine in women. Neurol Clin. 2009;27(2):503-11. doi:10.1016/j.ncl.2009.01.002

3. Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies. Headache. 2018;58(4):496-505. doi:10.1111/head.13281

4. Peck J, Urits I, Zeien J, et al. A comprehensive review of over-the-counter treatment for chronic migraine headaches. Curr Pain Headache Rep. 2020;24(5):19. doi: 10.1007/s11916-020-00852-0

5. Altabakhi IW, Anderson J, Zito PM. Acetaminophen/Aspirin/Caffeine. In: StatPearls [Internet]. StatPearls Publishing: 2021. Accessed June 30, 2021.

6. Vgontzas A, Burch R. Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks. Curr Pain Headache Rep. 2018 Oct 5;22(12):78. doi: 10.1007/s11916-018-0735-z

7. Kirthi V, Derry S, Moore RA, McQuay HJ. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;(4):CD008041. doi:10.1002/14651858.CD008041.pub2

8. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the a merican H eadache S ociety evidence assessment of migraine pharmacotherapies. Headache. 2015;55(1):3-20. doi:10.1111/head.12499

9. Diener HC, Bussone G, de Liano H, et al. Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks. Cephalalgia. 2004;24(11):947-54. doi:10.1111/j.1468-2982.2004.00783.x

10. Ray WA, Varas-Lorenzo C, Chung CP, et al. Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after hospitalization for serious coronary heart disease. Circ Cardiovasc Qual Outcomes. 2009 May;2(3):155-63. doi:10.1161/CIRCOUTCOMES.108.805689

11. Baena CP, D’Amico RC, Slongo H, Brunoni AR, Goulart AC, Benseñor I. The effectiveness of aspirin for migraine prophylaxis: a systematic review. Sao Paulo Med J. 2017;135(1):42-49. doi: 10.1590/1516-3180.2016.0165050916.

12. Rodés-Cabau J, Horlick E, Ibrahim R, et al. Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure: The CANOA Randomized Clinical Trial. JAMA. 2015;314(20):2147-54. doi:10.1001/jama.2015.13919.

13. Ingledue VF, Mounsey A. PURLs: treating migraine: the case for aspirin. J Fam Pract. 2014;63(2):94–96.

14. Electronic Aspirin: A new remedy for migraine. GlobalNewswire. June 17, 2019. https://www.globenewswire.com/en/news-release/2019/06/17/1869475/0/en/Electronic-Aspirin-A-new-remedy-for-migraine.html. Accessed June 30, 2021.

This article originally appeared on Neurology Advisor