Treating migraine: The case for aspirin

Illustrative case

During a routine physical, a 37-year-old patient asks you what she should take for her occasional migraines. She describes a unilateral headache with associated nausea, vomiting, phonophobia, and photophobia. What medication should you recommend?

Migraine headache affects more than 37 million Americans.² Women are 3 times more likely than men to suffer from migraine, with the highest prevalence among those between the ages of 30 and 50 years.^3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of 4 to 6 workdays each year due to migraine.^5,6

Do you recommend this low-cost option?

Although many patients try over-the-counter headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care providers.⁷ But despite a 2010 Cochrane review showing aspirin’s efficacy for acute migraine,⁸ our experience—based on discussions with physicians at numerous residency programs—suggests that family physicians are not likely to recommend it.

Further evidence of the underuse of aspirin for migraine comes from a 2013 review of national surveillance studies,⁵ which found that in 2009, triptans accounted for nearly 80% of antimigraine analgesics prescribed during office visits.⁵ Thus, when the Cochrane reviewers issued this update of the earlier meta-analysis, we welcomed the opportunity to feature a practice changer that might not be getting the “traction” it deserves.

STUDY SUMMARY: Multiple RCTs highlight aspirin's efficacy

The 2013 Cochrane reviewers used the same 13 good quality, double-blind RCTs involving 4222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5261 episodes of migraine of moderate to severe intensity were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.¹

Five studies had placebo controls, 4 had active controls (sumatriptan, zolmitriptan, ibuprofen, acetaminophen plus codeine, and ergotamine plus caffeine among them), and 4 had both active and placebo controls. Primary outcomes were pain-free status at 2 hours and headache relief (defined as a reduction in pain from moderate or severe to none or mild without the use of rescue medication) at 2 hours. Sustained headache relief at 24 hours was a secondary outcome.

Patients self-assessed their headache pain, using either a 4-point categorical scale (none, mild, moderate, or severe) or a 100 mm visual analog scale. On the analog scale, <30 mm was considered mild or no pain; ≥30 mm was considered moderate or severe.

Study participants were 18 to 65 years of age (the mean age range was 37-44), and their symptoms met International Headache Society criteria for migraine with or without aura.⁹ All participants had migraine symptoms for ≥12 months, with between one and 6 attacks of moderate to severe intensity per month prior to the study period.

In 6 studies (n=2027), investigators compared either 900 or 1000 mg aspirin alone with placebo. For both primary outcomes, aspirin alone was superior to placebo, with a number needed to treat (NNT) of 8.1 for 2-hour pain-free status and 4.9 for 2-hour headache relief. In 3 studies (n=1142), aspirin was superior to placebo for 24-hour headache relief, with an NNT of 6.6. Aspirin plus metoclopramide was also better than placebo for primary and secondary outcomes, with an NNT of 8.8 for 2-hour pain-free status, 3.3 for 2-hour headache relief, and 6.2 for 24-hour headache relief. Based on subgroup analysis, aspirin plus metoclopramide was more effective than aspirin alone for 2-hour headache relief (P=.0131), but equivalent for 2-hour pain-free status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea (P<.00006) and vomiting (P=.002).

In 2 studies (n=726), aspirin alone was equivalent to sumatriptan 50 mg for reaching pain-free and headache relief status at 2 hours. Two additional studies (n=523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for 2-hour headache relief, but the aspirin combination was inferior to the triptan for pain-free status at 2 hours (n=528). Data were insufficient to compare the efficacy of aspirin with zolmitriptan, ibuprofen, or acetaminophen plus codeine.

There were no reports of gastrointestinal bleed or other serious adverse events attributable to aspirin therapy. Most adverse effects were mild or moderate disturbances of the digestive and nervous systems, with a number needed to harm of 34 (95% confidence interval, 18-340) for aspirin (with or without metoclopramide) vs placebo.

WHAT'S NEW?: A reminder of aspirin's efficacy in treating migraine

The addition of metoclopramide to aspirin reduces nausea and vomiting, but offers little, if any, benefit for headache/pain relief.The update of this meta-analysis confirms that high-dose aspirin (900-1000 mg) is an effective treatment for migraine headache in adults between the ages of 18 and 65 years. The addition of metoclopramide reduces nausea and vomiting, but offers little if any benefit for headache/pain relief.

CAVEATS: Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other nonsteroidal anti-inflammatory drugs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients with chronic renal disease and/or a history of peptic ulcer disease.

CHALLENGES TO IMPLEMENTATION: Patients want a prescription

Patients often expect a prescription when they visit a physician with complaints of migraine headache and 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.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Illustrative case

During a routine physical, a 37-year-old patient asks you what she should take for her occasional migraines. She describes a unilateral headache with associated nausea, vomiting, phonophobia, and photophobia. What medication should you recommend?

Migraine headache affects more than 37 million Americans.² Women are 3 times more likely than men to suffer from migraine, with the highest prevalence among those between the ages of 30 and 50 years.^3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of 4 to 6 workdays each year due to migraine.^5,6

Do you recommend this low-cost option?

Although many patients try over-the-counter headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care providers.⁷ But despite a 2010 Cochrane review showing aspirin’s efficacy for acute migraine,⁸ our experience—based on discussions with physicians at numerous residency programs—suggests that family physicians are not likely to recommend it.

Further evidence of the underuse of aspirin for migraine comes from a 2013 review of national surveillance studies,⁵ which found that in 2009, triptans accounted for nearly 80% of antimigraine analgesics prescribed during office visits.⁵ Thus, when the Cochrane reviewers issued this update of the earlier meta-analysis, we welcomed the opportunity to feature a practice changer that might not be getting the “traction” it deserves.

STUDY SUMMARY: Multiple RCTs highlight aspirin's efficacy

The 2013 Cochrane reviewers used the same 13 good quality, double-blind RCTs involving 4222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5261 episodes of migraine of moderate to severe intensity were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.¹

Five studies had placebo controls, 4 had active controls (sumatriptan, zolmitriptan, ibuprofen, acetaminophen plus codeine, and ergotamine plus caffeine among them), and 4 had both active and placebo controls. Primary outcomes were pain-free status at 2 hours and headache relief (defined as a reduction in pain from moderate or severe to none or mild without the use of rescue medication) at 2 hours. Sustained headache relief at 24 hours was a secondary outcome.

Patients self-assessed their headache pain, using either a 4-point categorical scale (none, mild, moderate, or severe) or a 100 mm visual analog scale. On the analog scale, <30 mm was considered mild or no pain; ≥30 mm was considered moderate or severe.

Study participants were 18 to 65 years of age (the mean age range was 37-44), and their symptoms met International Headache Society criteria for migraine with or without aura.⁹ All participants had migraine symptoms for ≥12 months, with between one and 6 attacks of moderate to severe intensity per month prior to the study period.

In 6 studies (n=2027), investigators compared either 900 or 1000 mg aspirin alone with placebo. For both primary outcomes, aspirin alone was superior to placebo, with a number needed to treat (NNT) of 8.1 for 2-hour pain-free status and 4.9 for 2-hour headache relief. In 3 studies (n=1142), aspirin was superior to placebo for 24-hour headache relief, with an NNT of 6.6. Aspirin plus metoclopramide was also better than placebo for primary and secondary outcomes, with an NNT of 8.8 for 2-hour pain-free status, 3.3 for 2-hour headache relief, and 6.2 for 24-hour headache relief. Based on subgroup analysis, aspirin plus metoclopramide was more effective than aspirin alone for 2-hour headache relief (P=.0131), but equivalent for 2-hour pain-free status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea (P<.00006) and vomiting (P=.002).

In 2 studies (n=726), aspirin alone was equivalent to sumatriptan 50 mg for reaching pain-free and headache relief status at 2 hours. Two additional studies (n=523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for 2-hour headache relief, but the aspirin combination was inferior to the triptan for pain-free status at 2 hours (n=528). Data were insufficient to compare the efficacy of aspirin with zolmitriptan, ibuprofen, or acetaminophen plus codeine.

There were no reports of gastrointestinal bleed or other serious adverse events attributable to aspirin therapy. Most adverse effects were mild or moderate disturbances of the digestive and nervous systems, with a number needed to harm of 34 (95% confidence interval, 18-340) for aspirin (with or without metoclopramide) vs placebo.

WHAT'S NEW?: A reminder of aspirin's efficacy in treating migraine

The addition of metoclopramide to aspirin reduces nausea and vomiting, but offers little, if any, benefit for headache/pain relief.The update of this meta-analysis confirms that high-dose aspirin (900-1000 mg) is an effective treatment for migraine headache in adults between the ages of 18 and 65 years. The addition of metoclopramide reduces nausea and vomiting, but offers little if any benefit for headache/pain relief.

CAVEATS: Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other nonsteroidal anti-inflammatory drugs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients with chronic renal disease and/or a history of peptic ulcer disease.

CHALLENGES TO IMPLEMENTATION: Patients want a prescription

Patients often expect a prescription when they visit a physician with complaints of migraine headache and 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.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Illustrative case

During a routine physical, a 37-year-old patient asks you what she should take for her occasional migraines. She describes a unilateral headache with associated nausea, vomiting, phonophobia, and photophobia. What medication should you recommend?

Migraine headache affects more than 37 million Americans.² Women are 3 times more likely than men to suffer from migraine, with the highest prevalence among those between the ages of 30 and 50 years.^3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of 4 to 6 workdays each year due to migraine.^5,6

Do you recommend this low-cost option?

Although many patients try over-the-counter headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care providers.⁷ But despite a 2010 Cochrane review showing aspirin’s efficacy for acute migraine,⁸ our experience—based on discussions with physicians at numerous residency programs—suggests that family physicians are not likely to recommend it.

Further evidence of the underuse of aspirin for migraine comes from a 2013 review of national surveillance studies,⁵ which found that in 2009, triptans accounted for nearly 80% of antimigraine analgesics prescribed during office visits.⁵ Thus, when the Cochrane reviewers issued this update of the earlier meta-analysis, we welcomed the opportunity to feature a practice changer that might not be getting the “traction” it deserves.

STUDY SUMMARY: Multiple RCTs highlight aspirin's efficacy

The 2013 Cochrane reviewers used the same 13 good quality, double-blind RCTs involving 4222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5261 episodes of migraine of moderate to severe intensity were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.¹

Five studies had placebo controls, 4 had active controls (sumatriptan, zolmitriptan, ibuprofen, acetaminophen plus codeine, and ergotamine plus caffeine among them), and 4 had both active and placebo controls. Primary outcomes were pain-free status at 2 hours and headache relief (defined as a reduction in pain from moderate or severe to none or mild without the use of rescue medication) at 2 hours. Sustained headache relief at 24 hours was a secondary outcome.

Patients self-assessed their headache pain, using either a 4-point categorical scale (none, mild, moderate, or severe) or a 100 mm visual analog scale. On the analog scale, <30 mm was considered mild or no pain; ≥30 mm was considered moderate or severe.

Study participants were 18 to 65 years of age (the mean age range was 37-44), and their symptoms met International Headache Society criteria for migraine with or without aura.⁹ All participants had migraine symptoms for ≥12 months, with between one and 6 attacks of moderate to severe intensity per month prior to the study period.

In 6 studies (n=2027), investigators compared either 900 or 1000 mg aspirin alone with placebo. For both primary outcomes, aspirin alone was superior to placebo, with a number needed to treat (NNT) of 8.1 for 2-hour pain-free status and 4.9 for 2-hour headache relief. In 3 studies (n=1142), aspirin was superior to placebo for 24-hour headache relief, with an NNT of 6.6. Aspirin plus metoclopramide was also better than placebo for primary and secondary outcomes, with an NNT of 8.8 for 2-hour pain-free status, 3.3 for 2-hour headache relief, and 6.2 for 24-hour headache relief. Based on subgroup analysis, aspirin plus metoclopramide was more effective than aspirin alone for 2-hour headache relief (P=.0131), but equivalent for 2-hour pain-free status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea (P<.00006) and vomiting (P=.002).

In 2 studies (n=726), aspirin alone was equivalent to sumatriptan 50 mg for reaching pain-free and headache relief status at 2 hours. Two additional studies (n=523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for 2-hour headache relief, but the aspirin combination was inferior to the triptan for pain-free status at 2 hours (n=528). Data were insufficient to compare the efficacy of aspirin with zolmitriptan, ibuprofen, or acetaminophen plus codeine.

There were no reports of gastrointestinal bleed or other serious adverse events attributable to aspirin therapy. Most adverse effects were mild or moderate disturbances of the digestive and nervous systems, with a number needed to harm of 34 (95% confidence interval, 18-340) for aspirin (with or without metoclopramide) vs placebo.

WHAT'S NEW?: A reminder of aspirin's efficacy in treating migraine

The addition of metoclopramide to aspirin reduces nausea and vomiting, but offers little, if any, benefit for headache/pain relief.The update of this meta-analysis confirms that high-dose aspirin (900-1000 mg) is an effective treatment for migraine headache in adults between the ages of 18 and 65 years. The addition of metoclopramide reduces nausea and vomiting, but offers little if any benefit for headache/pain relief.

CAVEATS: Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other nonsteroidal anti-inflammatory drugs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients with chronic renal disease and/or a history of peptic ulcer disease.

CHALLENGES TO IMPLEMENTATION: Patients want a prescription

Patients often expect a prescription when they visit a physician with complaints of migraine headache and 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.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.