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Treating Migraine: The Case for Aspirin
High-dose aspirin is an effective treatment for acute migraine. So why aren’t more clinicians recommending it?

PRACTICE CHANGER

Recommend aspirin 975 mg (three adult tablets) as a viable firstline treatment for acute migraine. Consider prescribing metoclopramide 10 mg to be taken with aspirin to markedly decrease associated nausea and help achieve maximum symptom relief.1

STRENGTH OF RECOMMENDATION

B: Based on a Cochrane meta-analysis of 13 good-quality, randomized controlled trials (RCTs).1

ILLUSTRATIVE CASE

During a routine physical, a 37-year-old patient asks you what she should take for occasional migraine. 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 three times more likely than men to experience migraine, with the highest prevalence among those ages 30 to 50.3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of four to six workdays each year due to migraine.5,6

Do you recommend this low-cost option?

Although many patients try OTC headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care provider.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 practice providers 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.

Continue reading for the study summary... 

 

 

STUDY SUMMARY

Multiple RCTs highlight aspirin’s efficacy

The 2013 Cochrane reviewers used the same 13 good-quality, double-blind RCTs involving 4,222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5,261 episodes of moderate-to-severe migraine were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.1

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

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

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

In six studies (n = 2,027), investigators compared either 900- or 1,000-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 two-hour painfree status and 4.9 for two-hour headache relief. In three studies (n = 1,142), 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 two-hour painfree status, 3.3 for two-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 two-hour headache relief but equivalent for two-hour painfree status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea and vomiting.

In two studies (n = 726), aspirin alone was equivalent to sumatriptan 50 mg for reaching painfree and headache relief status at two hours. Two additional studies (n = 523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for two-hour headache relief, but the aspirin combination was inferior to the triptan for painfree status at two 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 bleeding 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 for aspirin (with or without metoclopramide) versus placebo.

WHAT’S NEW?

A reminder of aspirin’s efficacy in treating migraine

The update of this meta-analysis confirms that high-dose aspirin (900 to 1,000 mg) is an effective treatment for migraine headache in adults ages 18 to 65. The addition of metoclopramide reduces nausea and vomiting but offers little if any benefit for headache/pain relief.

Continue reading for the caveats and challenges to implementation... 

 

 

CAVEATS

Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other NSAIDs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients who have 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 present 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.

Continue reading for the references... 

 

 

REFERENCES

1. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008041.

2. National Headache Foundation. Migraine. www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed February 14, 2014.

3. Lipton RB, Stewart WF, Diamond S, et. al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646-657.

4. Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life-span study. Cephalagia. 2010; 9:1065-1072.

5. Smitherman TA, Burch R, Sheikh H, et al. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427-436.

6. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818.

7. Gibbs TS, Fleischer AB Jr, Feldman SR, et al. Health care utilization in patients with migraine: demographics and patterns of care in the ambulatory setting. Headache. 2003;43:330-335.

8. Kirthi V, Derry S, Moore RA, et al. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;(4):CD008041.

9. The international classification of headache disorders. 2nd ed. Cephalalgia. 2004; 24 (suppl 1):S9-S160.

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. 

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(2):94-96.

Author and Disclosure Information

Vickie F. Ingledue, MD, Anne Mounsey, MD
Vickie F. Ingledue and Anne Mounsey are in the Department of Family Medicine at the University of North Carolina at Chapel Hill.

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Vickie F. Ingledue, MD, Anne Mounsey, MD
Vickie F. Ingledue and Anne Mounsey are in the Department of Family Medicine at the University of North Carolina at Chapel Hill.

Author and Disclosure Information

Vickie F. Ingledue, MD, Anne Mounsey, MD
Vickie F. Ingledue and Anne Mounsey are in the Department of Family Medicine at the University of North Carolina at Chapel Hill.

High-dose aspirin is an effective treatment for acute migraine. So why aren’t more clinicians recommending it?
High-dose aspirin is an effective treatment for acute migraine. So why aren’t more clinicians recommending it?

PRACTICE CHANGER

Recommend aspirin 975 mg (three adult tablets) as a viable firstline treatment for acute migraine. Consider prescribing metoclopramide 10 mg to be taken with aspirin to markedly decrease associated nausea and help achieve maximum symptom relief.1

STRENGTH OF RECOMMENDATION

B: Based on a Cochrane meta-analysis of 13 good-quality, randomized controlled trials (RCTs).1

ILLUSTRATIVE CASE

During a routine physical, a 37-year-old patient asks you what she should take for occasional migraine. 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 three times more likely than men to experience migraine, with the highest prevalence among those ages 30 to 50.3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of four to six workdays each year due to migraine.5,6

Do you recommend this low-cost option?

Although many patients try OTC headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care provider.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 practice providers 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.

Continue reading for the study summary... 

 

 

STUDY SUMMARY

Multiple RCTs highlight aspirin’s efficacy

The 2013 Cochrane reviewers used the same 13 good-quality, double-blind RCTs involving 4,222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5,261 episodes of moderate-to-severe migraine were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.1

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

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

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

In six studies (n = 2,027), investigators compared either 900- or 1,000-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 two-hour painfree status and 4.9 for two-hour headache relief. In three studies (n = 1,142), 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 two-hour painfree status, 3.3 for two-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 two-hour headache relief but equivalent for two-hour painfree status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea and vomiting.

In two studies (n = 726), aspirin alone was equivalent to sumatriptan 50 mg for reaching painfree and headache relief status at two hours. Two additional studies (n = 523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for two-hour headache relief, but the aspirin combination was inferior to the triptan for painfree status at two 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 bleeding 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 for aspirin (with or without metoclopramide) versus placebo.

WHAT’S NEW?

A reminder of aspirin’s efficacy in treating migraine

The update of this meta-analysis confirms that high-dose aspirin (900 to 1,000 mg) is an effective treatment for migraine headache in adults ages 18 to 65. The addition of metoclopramide reduces nausea and vomiting but offers little if any benefit for headache/pain relief.

Continue reading for the caveats and challenges to implementation... 

 

 

CAVEATS

Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other NSAIDs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients who have 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 present 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.

Continue reading for the references... 

 

 

REFERENCES

1. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008041.

2. National Headache Foundation. Migraine. www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed February 14, 2014.

3. Lipton RB, Stewart WF, Diamond S, et. al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646-657.

4. Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life-span study. Cephalagia. 2010; 9:1065-1072.

5. Smitherman TA, Burch R, Sheikh H, et al. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427-436.

6. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818.

7. Gibbs TS, Fleischer AB Jr, Feldman SR, et al. Health care utilization in patients with migraine: demographics and patterns of care in the ambulatory setting. Headache. 2003;43:330-335.

8. Kirthi V, Derry S, Moore RA, et al. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;(4):CD008041.

9. The international classification of headache disorders. 2nd ed. Cephalalgia. 2004; 24 (suppl 1):S9-S160.

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. 

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(2):94-96.

PRACTICE CHANGER

Recommend aspirin 975 mg (three adult tablets) as a viable firstline treatment for acute migraine. Consider prescribing metoclopramide 10 mg to be taken with aspirin to markedly decrease associated nausea and help achieve maximum symptom relief.1

STRENGTH OF RECOMMENDATION

B: Based on a Cochrane meta-analysis of 13 good-quality, randomized controlled trials (RCTs).1

ILLUSTRATIVE CASE

During a routine physical, a 37-year-old patient asks you what she should take for occasional migraine. 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 three times more likely than men to experience migraine, with the highest prevalence among those ages 30 to 50.3,4 More than 50% of patients report that episodes cause severe impairment, resulting in an average loss of four to six workdays each year due to migraine.5,6

Do you recommend this low-cost option?

Although many patients try OTC headache remedies for migraine, when they do seek medical care for this condition, most (67%) turn to their primary care provider.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 practice providers 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.

Continue reading for the study summary... 

 

 

STUDY SUMMARY

Multiple RCTs highlight aspirin’s efficacy

The 2013 Cochrane reviewers used the same 13 good-quality, double-blind RCTs involving 4,222 participants as the earlier review; no new studies that warranted inclusion were found. A total of 5,261 episodes of moderate-to-severe migraine were treated with either aspirin alone or aspirin plus the antiemetic metoclopramide.1

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

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

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

In six studies (n = 2,027), investigators compared either 900- or 1,000-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 two-hour painfree status and 4.9 for two-hour headache relief. In three studies (n = 1,142), 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 two-hour painfree status, 3.3 for two-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 two-hour headache relief but equivalent for two-hour painfree status and 24-hour headache relief. The addition of metoclopramide to aspirin significantly reduced nausea and vomiting.

In two studies (n = 726), aspirin alone was equivalent to sumatriptan 50 mg for reaching painfree and headache relief status at two hours. Two additional studies (n = 523) compared aspirin plus metoclopramide with sumatriptan 100 mg and found them to be equal for two-hour headache relief, but the aspirin combination was inferior to the triptan for painfree status at two 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 bleeding 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 for aspirin (with or without metoclopramide) versus placebo.

WHAT’S NEW?

A reminder of aspirin’s efficacy in treating migraine

The update of this meta-analysis confirms that high-dose aspirin (900 to 1,000 mg) is an effective treatment for migraine headache in adults ages 18 to 65. The addition of metoclopramide reduces nausea and vomiting but offers little if any benefit for headache/pain relief.

Continue reading for the caveats and challenges to implementation... 

 

 

CAVEATS

Lack of comparison with other treatments

Data were insufficient to compare the efficacy of aspirin with zolmitriptan, other NSAIDs alone, or acetaminophen plus codeine. Aspirin should be used with caution in patients who have 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 present 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.

Continue reading for the references... 

 

 

REFERENCES

1. Kirthi V, Derry S, Moore RA. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2013;(4):CD008041.

2. National Headache Foundation. Migraine. www.headaches.org/education/Headache_Topic_Sheets/Migraine. Accessed February 14, 2014.

3. Lipton RB, Stewart WF, Diamond S, et. al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41:646-657.

4. Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life-span study. Cephalagia. 2010; 9:1065-1072.

5. Smitherman TA, Burch R, Sheikh H, et al. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427-436.

6. Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999; 159:813-818.

7. Gibbs TS, Fleischer AB Jr, Feldman SR, et al. Health care utilization in patients with migraine: demographics and patterns of care in the ambulatory setting. Headache. 2003;43:330-335.

8. Kirthi V, Derry S, Moore RA, et al. Aspirin with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010;(4):CD008041.

9. The international classification of headache disorders. 2nd ed. Cephalalgia. 2004; 24 (suppl 1):S9-S160.

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. 

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(2):94-96.

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Treating Migraine: The Case for Aspirin
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