ISSN 0017-8748 doi: 10.1111/head.12550 Published by Wiley Periodicals, Inc.
Headache © 2015 American Headache Society
Review Article Acute Migraine Treatment in Adults Werner J. Becker, MD, FRCPC
There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID–triptan combinations, dihydroergotamine, non-opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti-emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence-based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication overuse is eliminated or avoided. Migraine treatment is complex, and treatment must be individualized and tailored to the patient’s clinical features. Clinicians should make full use of available medications and formulations in an organized approach. Key words: migraine, acute, treatment, adult, triptan, nonsteroidal anti-inflammatory drug Abbreviations: AAC acetaminophen, ASA and caffeine, ASA acetylsalicylic acid, NNT number needed to treat, NSAIDs nonsteroidal anti-inflammatory drugs (Headache 2015;55:778-793)
The acute therapy of migraine has a long history, as patients and their physicians have tried to relieve the pain of migraine attacks. Caffeine was recommended for acute migraine treatment for hundreds of
years, and it was recognized over a century ago that patient response to medications for migraine attacks is idiosyncratic and that treatment must be tailored to the individual. This was based on the observation that measures that worked well in one case would fail in another apparently similar case.1,2
From the Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; The Hotchkiss Brain Institute, Calgary, Alberta, Canada. Address all correspondence to W.J. Becker, Division of Neurology, Foothills Hospital, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
Conflict of Interest: Dr. Becker has served on medical advisory boards for Allergan, Pfizer, Tribute, Amgen, ElectroCore, and St. Jude. He has received speaker’s honoraria from Serono, Allergan, Tribute, and Pfizer, and research support from St. Jude Medical, Pfizer, Allergan, and Amgen.
Accepted for publication February 20, 2015.
Financial Support: None.
778
Headache In the modern era in Western nations, acute medications for migraine attacks are used almost universally by migraine sufferers, with over 90% using some type of acute medication.3 Medication choice for the acute treatment of migraine attacks is not a simple matter, given the multiple medications available, and as has been recognized for over a century, one cannot predict which medication will work best for any given patient.2 Also, migraine attacks are generally treated in settings where the patient must usually act without outside assistance. The patient must therefore become an informed and knowledgeable member of the treatment team and partner with the health-care provider. The ability to take acute medications appropriately is an important skill which the patient must master, along with many other selfmanagement skills, if migraine is to be managed as successfully as possible. Pharmacological management is only one part of migraine management. It was pointed out over half a century ago that it was more important for a patient to live within his or her limitations, then to try an endless round of medications.4 Acute migraine medications have improved a great deal since that time, but this statement is still largely true. While patients differ in how severe their migraine tendency is, lifestyle and other environmental factors are very significant for many patients. Dealing with these may be difficult, and not all patients are willing to make the personal adjustments necessary for optimal migraine management.2 However, pharmacological management should be only one facet of a much broader approach to migraine management.5 Medication Choices.—Many different medications have been used, but the mainstays of modern acute migraine treatment are the nonsteroidal antiinflammatory drugs (NSAIDs) and the triptans. The evidence base for many acute migraine medications has recently been reviewed.6 Acetaminophen and NSAIDs.—Acetaminophen is widely used, and has randomized controlled trial evidence for efficacy in migraine,7,8 but is generally considered effective primarily for attacks of mild or moderate severity. As with the NSAIDs, it can be combined with an anti-emetic if the patient has significant nausea. A recent systematic review con-
779 cluded that acetaminophen 1000 mg plus metoclopramide 10 mg had 2-hour headache relief rates similar to those of sumatriptan 100 mg (39% vs 42%, respectively).9 NSAIDs.—The NSAIDs are generally a good starting point for acute migraine treatment, although acetaminophen can be tried if there are contraindications to NSAID use, and triptans are another option. Ibuprofen,10 naproxen sodium,11 acetylsalicylic acid (ASA),12 and diclofenac potassium13 all have double-blind randomized controlled trial evidence for efficacy that has been analyzed in systematic reviews. These NSAIDs have different pharmacokinetics, and this has implications for their usefulness in a specific patient. Ibuprofen and diclofenac potassium have very rapid absorption from the gastrointestinal tract, and therefore the potential for a rapid onset of action (Table 1). Although they may completely abort a migraine attack, their short half-life may make repeated dosing necessary for a single attack in some patients. Naproxen sodium, on the other hand, has slower absorption but a much longer half-life. Both ibuprofen and diclofenac potassium have special formulations with more rapid absorption and therefore a more rapid onset of action that have been shown to have advantages over their oral tablet counterparts. Solubilized ibuprofen 400 mg has generally shown a higher response rate for headache relief (headache reduced from moderate or severe intensity to mild or no headache) at 1 hour as compared to the corresponding standard ibuprofen tablet.14 Diclofenac potassium powder for oral solution (50 mg) has been compared directly to the corresponding oral tablet. For the pain free at 2 hours end point, the powdered formulation (sachets) was superior to the tablet, with 24.7% of patients pain free with the sachet, and 18.5% with the tablet (P = .0035). With the sachet, analgesic effects were noted within 15 minutes.15 ASA also has a relatively rapid absorption (Table 1), and an intermediate half-life of 5-6 hours if active metabolites are included. Effervescent ASA has a faster absorption than regular tablets.16 Ibuprofen is one of the most frequently used NSAIDs for migraine.3 This may reflect its low cost,
780
June 2015 Table 1.—Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs: Pharmacokinetic, NNTs, and Dosage
Drug
Acetaminophen Acetylsalicylic acid (ASA) (tablet)
ASA (effervescent)
Tmax (Hours)
0.5-1 1-2
∼20 minutes
Elimination Half-Life (Hours)
2 ASA: 0.25 Salicylate (active): 5-6 (after 1 g dose)
NNT: 2 Hour NNT: 2 Headache Hour Relief Pain Free
5.0
12
4.9
8.1
3.2
7.2
as above
Ibuprofen (tablet)
1-2
2
Ibuprofen (solubilized)
Headache © 2015 American Headache Society
Review Article Acute Migraine Treatment in Adults Werner J. Becker, MD, FRCPC
There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID–triptan combinations, dihydroergotamine, non-opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti-emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence-based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication overuse is eliminated or avoided. Migraine treatment is complex, and treatment must be individualized and tailored to the patient’s clinical features. Clinicians should make full use of available medications and formulations in an organized approach. Key words: migraine, acute, treatment, adult, triptan, nonsteroidal anti-inflammatory drug Abbreviations: AAC acetaminophen, ASA and caffeine, ASA acetylsalicylic acid, NNT number needed to treat, NSAIDs nonsteroidal anti-inflammatory drugs (Headache 2015;55:778-793)
The acute therapy of migraine has a long history, as patients and their physicians have tried to relieve the pain of migraine attacks. Caffeine was recommended for acute migraine treatment for hundreds of
years, and it was recognized over a century ago that patient response to medications for migraine attacks is idiosyncratic and that treatment must be tailored to the individual. This was based on the observation that measures that worked well in one case would fail in another apparently similar case.1,2
From the Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; The Hotchkiss Brain Institute, Calgary, Alberta, Canada. Address all correspondence to W.J. Becker, Division of Neurology, Foothills Hospital, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada.
Conflict of Interest: Dr. Becker has served on medical advisory boards for Allergan, Pfizer, Tribute, Amgen, ElectroCore, and St. Jude. He has received speaker’s honoraria from Serono, Allergan, Tribute, and Pfizer, and research support from St. Jude Medical, Pfizer, Allergan, and Amgen.
Accepted for publication February 20, 2015.
Financial Support: None.
778
Headache In the modern era in Western nations, acute medications for migraine attacks are used almost universally by migraine sufferers, with over 90% using some type of acute medication.3 Medication choice for the acute treatment of migraine attacks is not a simple matter, given the multiple medications available, and as has been recognized for over a century, one cannot predict which medication will work best for any given patient.2 Also, migraine attacks are generally treated in settings where the patient must usually act without outside assistance. The patient must therefore become an informed and knowledgeable member of the treatment team and partner with the health-care provider. The ability to take acute medications appropriately is an important skill which the patient must master, along with many other selfmanagement skills, if migraine is to be managed as successfully as possible. Pharmacological management is only one part of migraine management. It was pointed out over half a century ago that it was more important for a patient to live within his or her limitations, then to try an endless round of medications.4 Acute migraine medications have improved a great deal since that time, but this statement is still largely true. While patients differ in how severe their migraine tendency is, lifestyle and other environmental factors are very significant for many patients. Dealing with these may be difficult, and not all patients are willing to make the personal adjustments necessary for optimal migraine management.2 However, pharmacological management should be only one facet of a much broader approach to migraine management.5 Medication Choices.—Many different medications have been used, but the mainstays of modern acute migraine treatment are the nonsteroidal antiinflammatory drugs (NSAIDs) and the triptans. The evidence base for many acute migraine medications has recently been reviewed.6 Acetaminophen and NSAIDs.—Acetaminophen is widely used, and has randomized controlled trial evidence for efficacy in migraine,7,8 but is generally considered effective primarily for attacks of mild or moderate severity. As with the NSAIDs, it can be combined with an anti-emetic if the patient has significant nausea. A recent systematic review con-
779 cluded that acetaminophen 1000 mg plus metoclopramide 10 mg had 2-hour headache relief rates similar to those of sumatriptan 100 mg (39% vs 42%, respectively).9 NSAIDs.—The NSAIDs are generally a good starting point for acute migraine treatment, although acetaminophen can be tried if there are contraindications to NSAID use, and triptans are another option. Ibuprofen,10 naproxen sodium,11 acetylsalicylic acid (ASA),12 and diclofenac potassium13 all have double-blind randomized controlled trial evidence for efficacy that has been analyzed in systematic reviews. These NSAIDs have different pharmacokinetics, and this has implications for their usefulness in a specific patient. Ibuprofen and diclofenac potassium have very rapid absorption from the gastrointestinal tract, and therefore the potential for a rapid onset of action (Table 1). Although they may completely abort a migraine attack, their short half-life may make repeated dosing necessary for a single attack in some patients. Naproxen sodium, on the other hand, has slower absorption but a much longer half-life. Both ibuprofen and diclofenac potassium have special formulations with more rapid absorption and therefore a more rapid onset of action that have been shown to have advantages over their oral tablet counterparts. Solubilized ibuprofen 400 mg has generally shown a higher response rate for headache relief (headache reduced from moderate or severe intensity to mild or no headache) at 1 hour as compared to the corresponding standard ibuprofen tablet.14 Diclofenac potassium powder for oral solution (50 mg) has been compared directly to the corresponding oral tablet. For the pain free at 2 hours end point, the powdered formulation (sachets) was superior to the tablet, with 24.7% of patients pain free with the sachet, and 18.5% with the tablet (P = .0035). With the sachet, analgesic effects were noted within 15 minutes.15 ASA also has a relatively rapid absorption (Table 1), and an intermediate half-life of 5-6 hours if active metabolites are included. Effervescent ASA has a faster absorption than regular tablets.16 Ibuprofen is one of the most frequently used NSAIDs for migraine.3 This may reflect its low cost,
780
June 2015 Table 1.—Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs: Pharmacokinetic, NNTs, and Dosage
Drug
Acetaminophen Acetylsalicylic acid (ASA) (tablet)
ASA (effervescent)
Tmax (Hours)
0.5-1 1-2
∼20 minutes
Elimination Half-Life (Hours)
2 ASA: 0.25 Salicylate (active): 5-6 (after 1 g dose)
NNT: 2 Hour NNT: 2 Headache Hour Relief Pain Free
5.0
12
4.9
8.1
3.2
7.2
as above
Ibuprofen (tablet)
1-2
2
Ibuprofen (solubilized)
