D i a g n o s i s an d Management of Migraines a n d M i g r a i n e Va r i a n t s Tomia Palmer Harmon,
MD
KEYWORDS Migraine Treatment Medications NSAIDs Triptans Antiemetics KEY POINTS Migraine headache is a neurologic disorder that has been widely studied. There are several treatment options available for mild to severe migraine headache. Adults with mild to moderate migraine headache and vomiting should add an antiemetic to their regimen; children and adults with moderate to severe migraine should try parenteral therapies like sumatriptan nasal spray. Relaxation training and cognitive–behavioral therapy have a role in nonpharmacologic treatment options; surgical removal of trigger points has been found to be effective.
INTRODUCTION
A migraine headache is a complex brain event that takes place over hours to days.1 Migraine headache takes on many different forms and levels of severity. Additionally, migraine affects adults as well as children. Patients who may require preventive therapy include patients with more than 4 migraine headaches per month, patients with migraine headaches that last for more than 12 hours, and those who feel that migraine accounts for a significant amount of their total disability.2 Other patients who might require preventive therapy are those who have a resultant neurologic deficit secondary to migraine or those for whom the cost of acute therapy is prohibitive. The same symptomatology that leads to preventive therapy in adults applies to children. However, some patients are well-controlled with acute therapies. This article highlights treatment options for acute migraine in children and adults. PATIENT EVALUATION OVERVIEW
The diagnosis of migraine headache is made based on patient history of headaches that fit a set of diagnostic criteria (Box 1). Criteria set forth by Department of Clinical Education, Georgia Campus, Philadelphia College of Osteopathic Medicine, 625 Old Peachtree Road, Northwest, Suwanee, GA 30024, USA E-mail address: [email protected] Prim Care Clin Office Pract - (2015) -–http://dx.doi.org/10.1016/j.pop.2015.01.003 primarycare.theclinics.com 0095-4543/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
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Harmon
Box 1 Diagnostic criteria for migraine Migraine without aura A. At least 5 attacks fulfilling criteria B–D B. Headache attacks lasting 4–72 hours (untreated or unsuccessfully treated) C. Headache has 2 of the following characteristics: Unilateral location Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs) D. During headache 1 of the following: Nausea, vomiting, or both Photophobia and phonophobia E. Not better accounted for by another ICHD-3 diagnosis Migraine with aura A. At least 2 attacks fulfilling criterion B and C B. One or more of the following fully reversible aura symptoms: Visual Sensory Speech and/or language Motor Brainstem Retinal C. At least 2 of the following 4 characteristics: At least 1 aura symptom spreads gradually over 5 minutes, and/or 2 symptoms occur in succession Each individual aura symptom lasts 5–60 minutes At least 1 aura symptom is unilateral The aura is accompanied, or followed within 60 minutes, by headache D. Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded Migraine with typical aura A. At least 2 attacks fulfilling criteria B–D B. Aura consisting of visual, sensory, and/or speech/language symptoms, each fully reversible, but no motor, brainstem, or retinal symptoms C. At least 2 of the following 4 characteristics: At least 1 aura symptom spreads gradually over 5 minutes, and/or 2 symptoms occur in succession Each individual aura symptom lasts 5–60 minutes At least 1 aura symptom is unilateral The aura is accompanied, or followed within 60 minutes, by headache
Migraines and Migraine Variants
D. Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded Features of migraine in children Attacks may last 2–72 hours Headache is more often bilateral than in adults; an adult pattern of unilateral pain usually emerges in late adolescence or early adulthood Occipital headache is rare and raises diagnostic caution for structural lesions Photophobia and phonophobia may be inferred by behavior in young children Abbreviation: ICHD-3, International Classification of Headache Disorders, 3rd edition. Adapted from Headache Classification Committee of the International Headache Society (HIS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33:629.
the International Headache Society for acute migraine without aura are as follows3: 1. More than 5 attacks of the same type headache, lasting 4 to 72 hours 2. Headache (2 criteria must apply): a. Unilateral b. Throbbing or pulsating c. Aggravated by activity d. Moderate to severe intensity 3. Associated symptoms (1): a. Nausea or vomiting b. Phonophobia or photophobia Patients might also have other symptoms that are listed in the diagnostic criteria for migraine with aura, migraine with typical aura, and migraine in children. Those criteria are listed in Box 1. The International Headache Society also defines migraine as either episodic or chronic. Episodic migraine occurs on fewer than 15 days of the month for fewer than 3 months. Chronic migraine occurs on more than 15 days of the month for more than 3 months. Children with migraine headaches may not be able to express adequately their symptomatology. Neurologists suggest that children use headache drawings to try to illustrate their pain. Illustrations showing features like pounding pain, nausea/vomiting, and photophobia have been found to be 92.1% sensitive and 82.7% specific, with a positive predictive value of 87.1% for migraine.4 Studies have shown that the diagnostic criteria may have decreased sensitivity when children are seen in the emergency department. Therefore, a set of criteria have been proposed for the diagnosis of children in the emergency department.5 Four of the 6 criteria listed below should be met:
Moderate to severe episode of impaired daily activities Focal localization of headache Pulsatile description Nausea or vomiting or abdominal pain Photophobia or phonophobia or avoidance of light and noise Symptoms increasing with activity or resolving by rest.
Treatment of migraine is just as complex as diagnosis. There are pharmacologic and nonpharmacologic treatment options, as well as combination therapies and surgical treatment options.
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PHARMACOLOGIC TREATMENT OPTIONS
Treatment of migraine headache should mirror the severity of migraine and symptoms. A randomized, controlled, parallel-group clinical trial conducted by the Disability in Strategies Study Group in 13 countries has shown that early treatment of migraine with a large dose of medication deemed better clinical results compared with a stepwise approach.6,7 The study found that headache response at 2 hours across 6 attacks was 52.7% in the stratified care treatment group versus 40.6% in the step care across attacks group. Intensity of medication care should be linked to severity of symptoms.2 A patient who has mild to moderate migraines without nausea and vomiting should be given prescriptions for nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or combination analgesics. An antiemetic should be added to the NSAIDs, acetaminophen, or combination analgesic in the patient with mild to moderate migraines with nausea and vomiting. Patients with moderate to severe migraines without nausea and vomiting should be started on triptans or a combination of sumatriptan-naproxen (Treximet); those patients with nausea and vomiting in the setting of a moderate to severe migraine can try medications like nasal sumatriptan (Imitrex), parenteral dihydroergotamine (Migranal, D.H.E. 45), and antiemetics that can be given by a nonoral route (Table 1).2 For treatment of mild to moderate migraine, a review of UpToDate shows that the following NSAIDs have been found to be effective in the treatment of migraine headache in randomized, placebo-controlled trials8:
Aspirin (Ecotrin), 650 to 1000 mg Ibuprofen (Motrin), 400 to 1200 mg Naproxen (Aleve; Naprosyn), 750 to 1250 mg Diclofenac (Voltaren, Cataflam), 50 to 100 mg Diclofenac epolamine (Flector Patch), 65 mg Acetaminophen (Tylenol), 1000 mg Acetaminophen–aspirin–caffeine (Excedrin), 2 extra-strength tablets
Treximet (a proprietary formulation of sumatriptan 85 mg and naproxen 500 mg) has been recommended for patients who do not respond well to monotherapy. A randomized, placebo-controlled trial found that sumatriptan–naproxen was effective at reducing headache pain, photophobia, and phonophobia. A dose of naproxen 550 mg (over-the-counter formulation) and a single oral sumatriptan can be given to patients if cost is prohibitive.9 Metoclopramide (Reglan) at a dose of 10 mg antiemetic is used as an adjunctive therapy for mild to moderate migraine and has been found to decrease nausea and vomiting.10 Metoclopramide is used normally only in children in the emergency setting or when the child has extended migraine. Triptans have been found to be effective in the treatment of moderate to severe migraine headache.2 The oral triptans available to treatment of migraine headache without nausea and vomiting are as follows:
Eletriptan (Relpax), 40 mg Naratriptan (Amerge), 2.5 mg Rizatriptan (Maxalt), 5 or 10 mg Sumatriptan (Imitrex), 100 mg Zolmitriptan (Zomig), 2.5, 5, or 10 mg
But what happens if your patient has moderate to severe migraines and has concurrent nausea and vomiting? There are parenteral medications that can be used for treatment. Parenteral sumatriptan (Imitrex Injection, Imitrex Nasal Spray, and Zelrix)
Table 1 Acute therapies for migraine Group 1a
Group 2b
Specific
Group 3c
Group 4d
Group 5e
Acetaminophen plus codeine PO
Butalbital, aspirin, plus caffeine PO
Acetaminophen PO
Dexamethasone IV
Naratriptan PO
Butalbital, aspirin, caffeine, plus codeine PO
Ergotamine PO
Chlorpromazine IM
Hydrocortisone IV
Rizatriptan PO
Butorphanol IM
Ergotamine plus caffeine PO
Granisetron IV
Sumatriptan SC, IN, PO
Chlorpromazine IM, IV
Metoclopramide IM, PR
Lidocaine IV
Zolmitriptan PO
Diclofenac K, PO
DHE SC, IM, IV, IN
Ergotamine plus caffeine plus pentobarbital plus Bellafoline PO
DHE IV, plus antiemetic Nonspecific
Flurbiprofen, PO Isometheptene CPD, PO Ketorolac IM
Aspirin PO
Lidocaine IN
Butorphanol IN
Meperidine IM, IV
Ibuprofen PO
Methadone IM
Naproxen sodium PO
Metoclopramide IV
Prochlorperazine IV
Naproxen PO Prochlorperazine IM, PR
Abbreviations: IM, intramuscularly; IV, intravenously; PO, orally; PR, per rectum; SC, subcutaneously. a Proven, pronounced statistical and clinical benefit (2 double-blind, placebo-controlled studies and clinical impression of effect). b Moderate statistical and clinical benefit (1 double-blind, placebo-controlled study and clinical impression of effect). c Statistically but not proven clinically or clinically but not proven statistically effective (conflicting or inconsistent evidence). d Proven to be statistically or clinically ineffective (failed efficacy vs placebo). e Clinical and statistical benefits unknown (insufficient evidence available). From Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the quality standards subcommittee of the American academy of neurology. Neurology 2000;55(6):754–62; with permission.
Migraines and Migraine Variants
Acetaminophen, aspirin, plus caffeine PO
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has been used for treatment, as well as parenteral dihydroergotamine (given intramuscularly, subcutaneously, intravenously, or intranasally). The recommended doses are as follows11,12: Imitrex injection: 6 mg subcutaneously; may repeat if needed more than 1 hour after initial dose (maximum of two 6-mg injections in a 24-hour period). Imitrex nasal: 5 mg in 1 nostril; or 10 mg (5 mg in each nostril); or 20 mg. May repeat the dose in 2 hours if the headache returns. The dosage should not exceed 40 mg in 24 hours. Sumatriptan transdermal (Zelrix): One patch (6.5 mg) for 4 hours. May apply a second patch after the first patch has been on for no less than 2 hours. The patient may apply a maximum of 2 patches in a 24-hour period. Migranal IM or subcutaneous: 1 mg at first sign of migraine headache. The dose may be repeated every hour to a maximum dosage of 3 mg/d and 6 mg/wk. Migranal IV: 1 mg at first sign of migraine headache. The dose may be repeated hourly to a maximum dosage of 2 mg/d and 6 mg/wk. Migranal intranasal: 1 spray (0.5 mg) in each nostril at first sign of migraine headache. The dose may be repeated after 15 minutes to a maximum of 4 sprays (2 mg). The patient should not exceed 6 sprays (2 mg) in a 24-hour period and no more than 8 sprays (4 mg) in a week. PEDIATRICS
The treatment of migraine headache in children is very similar to treatment in adults. The suggested initial treatment is the use of a simple analgesic.13 The analgesics of choice are acetaminophen (Tylenol) or ibuprofen (Motrin, Advil). The doses are as follows: Ibuprofen (Motrin, Advil): 10 mg/kg at the onset of migraine headache. The dose may be repeated in 4 to 6 hours but should not exceed 4 doses in 24 hours (maximum of 40 mg/kg). Acetaminophen (Tylenol): 10 to 20 mg/kg (maximum of 1000 mg) at the onset of migraine headache. The dose may be repeated in 2 to 4 hours and the patient may not take more than 3 doses in 24 hours. Children who have mild to moderate migraine headaches with nausea and vomiting should be given an antiemetic. The antiemetic of choice is promethazine (Phenergan) 0.25 to 0.5 mg/kg per rectum. The dosage may be repeated every 4 to 6 hours as needed. Children who have migraine headaches without vomiting but do not respond to simple analgesics are treated with oral triptans. Sumatriptan (Imitrex oral) is the triptan of choice. The starting dose of oral sumatriptan is 25 mg (maximum dose of 50 mg). However, children who are unable to take sumatriptan may take either rizatriptan (Maxalt) 5 mg wafer, zolmitriptan (Zomig) 2.5 or 5 mg, or almotriptan (Axert) 6.25 or 12.5 mg. Rizatriptan and zolmitriptan are preferred for children with early nausea and vomiting because they are available in orally disintegrating formulations. A combination of oral sumatriptan-naproxen is recommended for children with migraine and no vomiting who do not respond to monotherapy with other medications. A randomized, parallel group of 12 to 17 year olds was studied to determine with pain free rates from baseline after 2 hours.2 Sumatriptan-naproxen doses of 10/60 mg, 30/180 mg, and 85/500 mg were studied with significant differences found at the 85/500 mg dose versus placebo (23% vs 9%; P 5 .008). Children who are at least 5 years old and do not respond to analgesics, have persistent vomiting, and cannot take the orally disintegrating formulations should use
Migraines and Migraine Variants
sumatriptan (Imitrex) nasal spray, starting with a 5-mg dose. The dose can be repeated once in 4 to 6 hours if the child initially felt relief from the migraine headache but the headache returned. Children who felt no relief should try the 10 mg nasal spray (two 5-mg sprays given together). The nasal spray may be used at a higher dosage (maximum of 20 mg) in older children. Children are asked to suck a hard piece of candy after using the nasal spray because the spray leaves a bad taste in the mouth. Zolmitriptan (Zomig) nasal spray (5 mg) may be used if the child does not like or want to use sumatriptan nasal spray.13 NONPHARMACOLOGIC TREATMENT OPTIONS
The American Academy of Neurology (AAN) made recommendations in 2000 for nonpharmacologic treatment of migraine.14 The AAN recommended relaxation training, thermal biofeedback combined with relaxation training, electromyographic biofeedback, and cognitive–behavioral therapy, but the AAN was unable to state what type of patient would benefit best from these therapies. The AAN also suggested that behavioral therapy would work well with preventative drug therapy. The AAN could not make recommendations for the use of hypnosis, acupuncture, transcutaneous electrical nerve stimulation, chiropractic or osteopathic cervical manipulation, occlusal adjustment (adjusting patient’s bite), or hyperbaric oxygen. SURGICAL TREATMENT OPTIONS
Patients who have been unable to find relief with pharmacologic and nonpharmacologic options can seek out surgical treatment. One surgery involves the removal of trigger sites for headache.15 The surgical deactivation of migraine trigger sites has been found to be an effective treatment for patients who have frequent moderate to severe migraine headaches. Another option that has been recommended in the past was closure of the patent foramen ovale. However, a retrospective analysis of the procedure showed low availability of evidence to conclude that the surgery is effective.16 MIGRAINE VARIANTS
Migraine variants include hemiplegic migraine (either familial or sporadic), menstrual migraine, basilar-type migraine, and retinal migraine. Hemiplegic migraine is characterized by motor weakness on 1 side of the body during a migraine attack. Basilar type migraine is associated with blurred vision, syncope, and ataxia. Menstrual migraine occurs 2 days before to 3 days after the beginning of a menstrual cycle. Retinal migraine is characterized by visual disturbances or blindness for up to 1 hour (Table 2).3 Table 2 Migraine variants Migraine Variant
Onset
Characterization
Basilar
During migraine
Blurred vision, syncope, ataxia
Hemiplegic
During migraine
Motor weakness on one side of the body
Menstrual
Two days before to 3 d after beginning of menstrual cycle
Typical migraine
Retinal
During migraine
Visual disturbances of blindness for 1 h
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Table 3 Treatment of migraines Recommended Start Time
Age Group
Severity of Migraine
Medication
Adult (>18 y old)
Mild to moderate
NSAIDs (aspirin, ibuprofen, naproxen, etc) Treximet NSAID or Treximet plus Metoclopramide Triptans (Eletriptan, Naratriptan, etc) Parenteral (Imitrex injection, Imitrex nasal, Zelrix, Migranal, etc)
Onset of migraine
NSAIDs (Acetaminophen or Ibuprofen) NSAIDs plus Promethazine
Onset of migraine
Triptans (sumatriptan preferred)
Onset of migraine
Combination Sumatriptan-Naproxen
Onset of migraine
Sumatriptan nasal spray
Onset of migraine
Mild to moderate with nausea and vomiting Moderate to Severe Moderate to severe with nausea and vomiting Children
Mild to moderate Mild to moderate with nausea and vomiting Mild to moderate unresponsive to simple analgesics Mild to moderate with no vomiting and unresponsive to monotherapy At least 5 y old and unresponsive to analgesics with persistent vomiting and unable to take orally disintegrating formulations
Onset of migraine Onset of migraine Onset of migraine
Onset of migraine
Abbreviation: NSAIDs, nonsteroidal anti-inflammatory drugs.
SUMMARY
The acute treatment of migraine should start early with an effective dose. Children and adults should start with simple analgesics for mild to moderate migraine headaches without vomiting. Those children and adults who do not respond to monotherapy can try sumatriptan–naproxen (Treximet) as a treatment strategy. Adults with mild to moderate migraine headache and vomiting should add an antiemetic to their regimen. Metoclopramide is recommended for adult patients; promethazine is recommended for children. Finally, children and adults with moderate to severe migraine should try parenteral therapies like sumatriptan nasal spray (Table 3). Relaxation training and cognitive behavioral therapy have a role in nonpharmacologic treatment options and surgical removal of trigger points has been found to be effective.15
REFERENCES
1. Charles A. The evolution of a migraine attack- a review of recent evidence. Headache 2013;53(2):413. 2. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2000;55(6):754–62.
Migraines and Migraine Variants
3. Headache Classification Committee of the International Headache Society (HIS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33(9):629–808. 4. Stafstrom CE, Rostasy K, Minster A. The usefulness of children’s drawings in the diagnosis of headache. Pediatrics 2002;109(3):460. 5. Trottier ED, Bailey B, Lucas N, et al. Diagnosis of migraine in the pediatric emergency department. Pediatr Neurol 2013;49(1):40–5. 6. Lipton RB, Stewart WF, Stone AM, et al. Stratified care vs. step care strategies for migraine: the disability in strategies of care (DISC) study; a randomized trial. JAMA 2000;284(20):2599. 7. UpToDate. Acute treatment of migraine in adults. 2014. Available at: http://www. uptodate.com/contents/acute-treatment-of-migraine-in-adults?source5search_ result&search5acute1treatment1of1migraine&selectedTitle51%7E150. Accessed March 24, 2014. 8. Brandes JL, Kudrow D, Start SR, et al. Sumatriptan-naproxen for acute treatment of migraine; a randomized trial. JAMA 2007;297(13):1443. 9. Tfelt-Hansen P, Henry P, Mulder LJ, et al. The effectiveness of combined oral lysine acetysalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet 1995;346(8980):923. 10. UpToDate. Sumatriptan: drug information lexicomp. Available at: http://www.uptodate. com/contents/sumatriptan-drug-information?source5see_link&utdPopup5true. Accessed March 26, 2014. 11. UpToDate. Dihydroergotamine: drug information lexicomp. Available at: http:// www.uptodate.com/contents/dihydroergotamine-drug-information?source5see_ link&utdPopup5true. Accessed March 26, 2014. 12. UpToDate. Management of migraine headache in children. 2014. Available at: http://www.uptodate.com/contents/management-of-migraine-headache-inchildren?source5search_result&search5migraine1in1children&selectedTitle5 2%7E150#H29. Accessed March 27, 2014. 13. Derosier FJ, Lewis D, Hershey AD, et al. Randomized trial of sumatriptan and naproxen sodium combination in adolescent migraine. Pediatrics 2013;129(6):e1411. 14. Guyuron B, Reed D, Kriegler JS, et al. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg 2009;124(2):461. 15. Schwedt TJ, Demaerschalk BM, Dodick DW. Patent foramen ovale and migraine; a quantitative systematic review. Cephalalgia 2008;28(5):531. 16. UpToDate. Preventive treatment of migraine in adults. 2014. Available at: http://www. uptodate.com/contents/preventive-treatment-of-migraine-in-adults?source5 search_result&search5migraine1prevention&selectedTitle51%7E150. Accessed March 31, 2014.
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KEYWORDS Migraine Treatment Medications NSAIDs Triptans Antiemetics KEY POINTS Migraine headache is a neurologic disorder that has been widely studied. There are several treatment options available for mild to severe migraine headache. Adults with mild to moderate migraine headache and vomiting should add an antiemetic to their regimen; children and adults with moderate to severe migraine should try parenteral therapies like sumatriptan nasal spray. Relaxation training and cognitive–behavioral therapy have a role in nonpharmacologic treatment options; surgical removal of trigger points has been found to be effective.
INTRODUCTION
A migraine headache is a complex brain event that takes place over hours to days.1 Migraine headache takes on many different forms and levels of severity. Additionally, migraine affects adults as well as children. Patients who may require preventive therapy include patients with more than 4 migraine headaches per month, patients with migraine headaches that last for more than 12 hours, and those who feel that migraine accounts for a significant amount of their total disability.2 Other patients who might require preventive therapy are those who have a resultant neurologic deficit secondary to migraine or those for whom the cost of acute therapy is prohibitive. The same symptomatology that leads to preventive therapy in adults applies to children. However, some patients are well-controlled with acute therapies. This article highlights treatment options for acute migraine in children and adults. PATIENT EVALUATION OVERVIEW
The diagnosis of migraine headache is made based on patient history of headaches that fit a set of diagnostic criteria (Box 1). Criteria set forth by Department of Clinical Education, Georgia Campus, Philadelphia College of Osteopathic Medicine, 625 Old Peachtree Road, Northwest, Suwanee, GA 30024, USA E-mail address: [email protected] Prim Care Clin Office Pract - (2015) -–http://dx.doi.org/10.1016/j.pop.2015.01.003 primarycare.theclinics.com 0095-4543/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
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Harmon
Box 1 Diagnostic criteria for migraine Migraine without aura A. At least 5 attacks fulfilling criteria B–D B. Headache attacks lasting 4–72 hours (untreated or unsuccessfully treated) C. Headache has 2 of the following characteristics: Unilateral location Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs) D. During headache 1 of the following: Nausea, vomiting, or both Photophobia and phonophobia E. Not better accounted for by another ICHD-3 diagnosis Migraine with aura A. At least 2 attacks fulfilling criterion B and C B. One or more of the following fully reversible aura symptoms: Visual Sensory Speech and/or language Motor Brainstem Retinal C. At least 2 of the following 4 characteristics: At least 1 aura symptom spreads gradually over 5 minutes, and/or 2 symptoms occur in succession Each individual aura symptom lasts 5–60 minutes At least 1 aura symptom is unilateral The aura is accompanied, or followed within 60 minutes, by headache D. Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded Migraine with typical aura A. At least 2 attacks fulfilling criteria B–D B. Aura consisting of visual, sensory, and/or speech/language symptoms, each fully reversible, but no motor, brainstem, or retinal symptoms C. At least 2 of the following 4 characteristics: At least 1 aura symptom spreads gradually over 5 minutes, and/or 2 symptoms occur in succession Each individual aura symptom lasts 5–60 minutes At least 1 aura symptom is unilateral The aura is accompanied, or followed within 60 minutes, by headache
Migraines and Migraine Variants
D. Not better accounted for by another ICHD-3 diagnosis, and transient ischemic attack has been excluded Features of migraine in children Attacks may last 2–72 hours Headache is more often bilateral than in adults; an adult pattern of unilateral pain usually emerges in late adolescence or early adulthood Occipital headache is rare and raises diagnostic caution for structural lesions Photophobia and phonophobia may be inferred by behavior in young children Abbreviation: ICHD-3, International Classification of Headache Disorders, 3rd edition. Adapted from Headache Classification Committee of the International Headache Society (HIS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33:629.
the International Headache Society for acute migraine without aura are as follows3: 1. More than 5 attacks of the same type headache, lasting 4 to 72 hours 2. Headache (2 criteria must apply): a. Unilateral b. Throbbing or pulsating c. Aggravated by activity d. Moderate to severe intensity 3. Associated symptoms (1): a. Nausea or vomiting b. Phonophobia or photophobia Patients might also have other symptoms that are listed in the diagnostic criteria for migraine with aura, migraine with typical aura, and migraine in children. Those criteria are listed in Box 1. The International Headache Society also defines migraine as either episodic or chronic. Episodic migraine occurs on fewer than 15 days of the month for fewer than 3 months. Chronic migraine occurs on more than 15 days of the month for more than 3 months. Children with migraine headaches may not be able to express adequately their symptomatology. Neurologists suggest that children use headache drawings to try to illustrate their pain. Illustrations showing features like pounding pain, nausea/vomiting, and photophobia have been found to be 92.1% sensitive and 82.7% specific, with a positive predictive value of 87.1% for migraine.4 Studies have shown that the diagnostic criteria may have decreased sensitivity when children are seen in the emergency department. Therefore, a set of criteria have been proposed for the diagnosis of children in the emergency department.5 Four of the 6 criteria listed below should be met:
Moderate to severe episode of impaired daily activities Focal localization of headache Pulsatile description Nausea or vomiting or abdominal pain Photophobia or phonophobia or avoidance of light and noise Symptoms increasing with activity or resolving by rest.
Treatment of migraine is just as complex as diagnosis. There are pharmacologic and nonpharmacologic treatment options, as well as combination therapies and surgical treatment options.
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Harmon
PHARMACOLOGIC TREATMENT OPTIONS
Treatment of migraine headache should mirror the severity of migraine and symptoms. A randomized, controlled, parallel-group clinical trial conducted by the Disability in Strategies Study Group in 13 countries has shown that early treatment of migraine with a large dose of medication deemed better clinical results compared with a stepwise approach.6,7 The study found that headache response at 2 hours across 6 attacks was 52.7% in the stratified care treatment group versus 40.6% in the step care across attacks group. Intensity of medication care should be linked to severity of symptoms.2 A patient who has mild to moderate migraines without nausea and vomiting should be given prescriptions for nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or combination analgesics. An antiemetic should be added to the NSAIDs, acetaminophen, or combination analgesic in the patient with mild to moderate migraines with nausea and vomiting. Patients with moderate to severe migraines without nausea and vomiting should be started on triptans or a combination of sumatriptan-naproxen (Treximet); those patients with nausea and vomiting in the setting of a moderate to severe migraine can try medications like nasal sumatriptan (Imitrex), parenteral dihydroergotamine (Migranal, D.H.E. 45), and antiemetics that can be given by a nonoral route (Table 1).2 For treatment of mild to moderate migraine, a review of UpToDate shows that the following NSAIDs have been found to be effective in the treatment of migraine headache in randomized, placebo-controlled trials8:
Aspirin (Ecotrin), 650 to 1000 mg Ibuprofen (Motrin), 400 to 1200 mg Naproxen (Aleve; Naprosyn), 750 to 1250 mg Diclofenac (Voltaren, Cataflam), 50 to 100 mg Diclofenac epolamine (Flector Patch), 65 mg Acetaminophen (Tylenol), 1000 mg Acetaminophen–aspirin–caffeine (Excedrin), 2 extra-strength tablets
Treximet (a proprietary formulation of sumatriptan 85 mg and naproxen 500 mg) has been recommended for patients who do not respond well to monotherapy. A randomized, placebo-controlled trial found that sumatriptan–naproxen was effective at reducing headache pain, photophobia, and phonophobia. A dose of naproxen 550 mg (over-the-counter formulation) and a single oral sumatriptan can be given to patients if cost is prohibitive.9 Metoclopramide (Reglan) at a dose of 10 mg antiemetic is used as an adjunctive therapy for mild to moderate migraine and has been found to decrease nausea and vomiting.10 Metoclopramide is used normally only in children in the emergency setting or when the child has extended migraine. Triptans have been found to be effective in the treatment of moderate to severe migraine headache.2 The oral triptans available to treatment of migraine headache without nausea and vomiting are as follows:
Eletriptan (Relpax), 40 mg Naratriptan (Amerge), 2.5 mg Rizatriptan (Maxalt), 5 or 10 mg Sumatriptan (Imitrex), 100 mg Zolmitriptan (Zomig), 2.5, 5, or 10 mg
But what happens if your patient has moderate to severe migraines and has concurrent nausea and vomiting? There are parenteral medications that can be used for treatment. Parenteral sumatriptan (Imitrex Injection, Imitrex Nasal Spray, and Zelrix)
Table 1 Acute therapies for migraine Group 1a
Group 2b
Specific
Group 3c
Group 4d
Group 5e
Acetaminophen plus codeine PO
Butalbital, aspirin, plus caffeine PO
Acetaminophen PO
Dexamethasone IV
Naratriptan PO
Butalbital, aspirin, caffeine, plus codeine PO
Ergotamine PO
Chlorpromazine IM
Hydrocortisone IV
Rizatriptan PO
Butorphanol IM
Ergotamine plus caffeine PO
Granisetron IV
Sumatriptan SC, IN, PO
Chlorpromazine IM, IV
Metoclopramide IM, PR
Lidocaine IV
Zolmitriptan PO
Diclofenac K, PO
DHE SC, IM, IV, IN
Ergotamine plus caffeine plus pentobarbital plus Bellafoline PO
DHE IV, plus antiemetic Nonspecific
Flurbiprofen, PO Isometheptene CPD, PO Ketorolac IM
Aspirin PO
Lidocaine IN
Butorphanol IN
Meperidine IM, IV
Ibuprofen PO
Methadone IM
Naproxen sodium PO
Metoclopramide IV
Prochlorperazine IV
Naproxen PO Prochlorperazine IM, PR
Abbreviations: IM, intramuscularly; IV, intravenously; PO, orally; PR, per rectum; SC, subcutaneously. a Proven, pronounced statistical and clinical benefit (2 double-blind, placebo-controlled studies and clinical impression of effect). b Moderate statistical and clinical benefit (1 double-blind, placebo-controlled study and clinical impression of effect). c Statistically but not proven clinically or clinically but not proven statistically effective (conflicting or inconsistent evidence). d Proven to be statistically or clinically ineffective (failed efficacy vs placebo). e Clinical and statistical benefits unknown (insufficient evidence available). From Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the quality standards subcommittee of the American academy of neurology. Neurology 2000;55(6):754–62; with permission.
Migraines and Migraine Variants
Acetaminophen, aspirin, plus caffeine PO
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has been used for treatment, as well as parenteral dihydroergotamine (given intramuscularly, subcutaneously, intravenously, or intranasally). The recommended doses are as follows11,12: Imitrex injection: 6 mg subcutaneously; may repeat if needed more than 1 hour after initial dose (maximum of two 6-mg injections in a 24-hour period). Imitrex nasal: 5 mg in 1 nostril; or 10 mg (5 mg in each nostril); or 20 mg. May repeat the dose in 2 hours if the headache returns. The dosage should not exceed 40 mg in 24 hours. Sumatriptan transdermal (Zelrix): One patch (6.5 mg) for 4 hours. May apply a second patch after the first patch has been on for no less than 2 hours. The patient may apply a maximum of 2 patches in a 24-hour period. Migranal IM or subcutaneous: 1 mg at first sign of migraine headache. The dose may be repeated every hour to a maximum dosage of 3 mg/d and 6 mg/wk. Migranal IV: 1 mg at first sign of migraine headache. The dose may be repeated hourly to a maximum dosage of 2 mg/d and 6 mg/wk. Migranal intranasal: 1 spray (0.5 mg) in each nostril at first sign of migraine headache. The dose may be repeated after 15 minutes to a maximum of 4 sprays (2 mg). The patient should not exceed 6 sprays (2 mg) in a 24-hour period and no more than 8 sprays (4 mg) in a week. PEDIATRICS
The treatment of migraine headache in children is very similar to treatment in adults. The suggested initial treatment is the use of a simple analgesic.13 The analgesics of choice are acetaminophen (Tylenol) or ibuprofen (Motrin, Advil). The doses are as follows: Ibuprofen (Motrin, Advil): 10 mg/kg at the onset of migraine headache. The dose may be repeated in 4 to 6 hours but should not exceed 4 doses in 24 hours (maximum of 40 mg/kg). Acetaminophen (Tylenol): 10 to 20 mg/kg (maximum of 1000 mg) at the onset of migraine headache. The dose may be repeated in 2 to 4 hours and the patient may not take more than 3 doses in 24 hours. Children who have mild to moderate migraine headaches with nausea and vomiting should be given an antiemetic. The antiemetic of choice is promethazine (Phenergan) 0.25 to 0.5 mg/kg per rectum. The dosage may be repeated every 4 to 6 hours as needed. Children who have migraine headaches without vomiting but do not respond to simple analgesics are treated with oral triptans. Sumatriptan (Imitrex oral) is the triptan of choice. The starting dose of oral sumatriptan is 25 mg (maximum dose of 50 mg). However, children who are unable to take sumatriptan may take either rizatriptan (Maxalt) 5 mg wafer, zolmitriptan (Zomig) 2.5 or 5 mg, or almotriptan (Axert) 6.25 or 12.5 mg. Rizatriptan and zolmitriptan are preferred for children with early nausea and vomiting because they are available in orally disintegrating formulations. A combination of oral sumatriptan-naproxen is recommended for children with migraine and no vomiting who do not respond to monotherapy with other medications. A randomized, parallel group of 12 to 17 year olds was studied to determine with pain free rates from baseline after 2 hours.2 Sumatriptan-naproxen doses of 10/60 mg, 30/180 mg, and 85/500 mg were studied with significant differences found at the 85/500 mg dose versus placebo (23% vs 9%; P 5 .008). Children who are at least 5 years old and do not respond to analgesics, have persistent vomiting, and cannot take the orally disintegrating formulations should use
Migraines and Migraine Variants
sumatriptan (Imitrex) nasal spray, starting with a 5-mg dose. The dose can be repeated once in 4 to 6 hours if the child initially felt relief from the migraine headache but the headache returned. Children who felt no relief should try the 10 mg nasal spray (two 5-mg sprays given together). The nasal spray may be used at a higher dosage (maximum of 20 mg) in older children. Children are asked to suck a hard piece of candy after using the nasal spray because the spray leaves a bad taste in the mouth. Zolmitriptan (Zomig) nasal spray (5 mg) may be used if the child does not like or want to use sumatriptan nasal spray.13 NONPHARMACOLOGIC TREATMENT OPTIONS
The American Academy of Neurology (AAN) made recommendations in 2000 for nonpharmacologic treatment of migraine.14 The AAN recommended relaxation training, thermal biofeedback combined with relaxation training, electromyographic biofeedback, and cognitive–behavioral therapy, but the AAN was unable to state what type of patient would benefit best from these therapies. The AAN also suggested that behavioral therapy would work well with preventative drug therapy. The AAN could not make recommendations for the use of hypnosis, acupuncture, transcutaneous electrical nerve stimulation, chiropractic or osteopathic cervical manipulation, occlusal adjustment (adjusting patient’s bite), or hyperbaric oxygen. SURGICAL TREATMENT OPTIONS
Patients who have been unable to find relief with pharmacologic and nonpharmacologic options can seek out surgical treatment. One surgery involves the removal of trigger sites for headache.15 The surgical deactivation of migraine trigger sites has been found to be an effective treatment for patients who have frequent moderate to severe migraine headaches. Another option that has been recommended in the past was closure of the patent foramen ovale. However, a retrospective analysis of the procedure showed low availability of evidence to conclude that the surgery is effective.16 MIGRAINE VARIANTS
Migraine variants include hemiplegic migraine (either familial or sporadic), menstrual migraine, basilar-type migraine, and retinal migraine. Hemiplegic migraine is characterized by motor weakness on 1 side of the body during a migraine attack. Basilar type migraine is associated with blurred vision, syncope, and ataxia. Menstrual migraine occurs 2 days before to 3 days after the beginning of a menstrual cycle. Retinal migraine is characterized by visual disturbances or blindness for up to 1 hour (Table 2).3 Table 2 Migraine variants Migraine Variant
Onset
Characterization
Basilar
During migraine
Blurred vision, syncope, ataxia
Hemiplegic
During migraine
Motor weakness on one side of the body
Menstrual
Two days before to 3 d after beginning of menstrual cycle
Typical migraine
Retinal
During migraine
Visual disturbances of blindness for 1 h
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Table 3 Treatment of migraines Recommended Start Time
Age Group
Severity of Migraine
Medication
Adult (>18 y old)
Mild to moderate
NSAIDs (aspirin, ibuprofen, naproxen, etc) Treximet NSAID or Treximet plus Metoclopramide Triptans (Eletriptan, Naratriptan, etc) Parenteral (Imitrex injection, Imitrex nasal, Zelrix, Migranal, etc)
Onset of migraine
NSAIDs (Acetaminophen or Ibuprofen) NSAIDs plus Promethazine
Onset of migraine
Triptans (sumatriptan preferred)
Onset of migraine
Combination Sumatriptan-Naproxen
Onset of migraine
Sumatriptan nasal spray
Onset of migraine
Mild to moderate with nausea and vomiting Moderate to Severe Moderate to severe with nausea and vomiting Children
Mild to moderate Mild to moderate with nausea and vomiting Mild to moderate unresponsive to simple analgesics Mild to moderate with no vomiting and unresponsive to monotherapy At least 5 y old and unresponsive to analgesics with persistent vomiting and unable to take orally disintegrating formulations
Onset of migraine Onset of migraine Onset of migraine
Onset of migraine
Abbreviation: NSAIDs, nonsteroidal anti-inflammatory drugs.
SUMMARY
The acute treatment of migraine should start early with an effective dose. Children and adults should start with simple analgesics for mild to moderate migraine headaches without vomiting. Those children and adults who do not respond to monotherapy can try sumatriptan–naproxen (Treximet) as a treatment strategy. Adults with mild to moderate migraine headache and vomiting should add an antiemetic to their regimen. Metoclopramide is recommended for adult patients; promethazine is recommended for children. Finally, children and adults with moderate to severe migraine should try parenteral therapies like sumatriptan nasal spray (Table 3). Relaxation training and cognitive behavioral therapy have a role in nonpharmacologic treatment options and surgical removal of trigger points has been found to be effective.15
REFERENCES
1. Charles A. The evolution of a migraine attack- a review of recent evidence. Headache 2013;53(2):413. 2. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2000;55(6):754–62.
Migraines and Migraine Variants
3. Headache Classification Committee of the International Headache Society (HIS). The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013;33(9):629–808. 4. Stafstrom CE, Rostasy K, Minster A. The usefulness of children’s drawings in the diagnosis of headache. Pediatrics 2002;109(3):460. 5. Trottier ED, Bailey B, Lucas N, et al. Diagnosis of migraine in the pediatric emergency department. Pediatr Neurol 2013;49(1):40–5. 6. Lipton RB, Stewart WF, Stone AM, et al. Stratified care vs. step care strategies for migraine: the disability in strategies of care (DISC) study; a randomized trial. JAMA 2000;284(20):2599. 7. UpToDate. Acute treatment of migraine in adults. 2014. Available at: http://www. uptodate.com/contents/acute-treatment-of-migraine-in-adults?source5search_ result&search5acute1treatment1of1migraine&selectedTitle51%7E150. Accessed March 24, 2014. 8. Brandes JL, Kudrow D, Start SR, et al. Sumatriptan-naproxen for acute treatment of migraine; a randomized trial. JAMA 2007;297(13):1443. 9. Tfelt-Hansen P, Henry P, Mulder LJ, et al. The effectiveness of combined oral lysine acetysalicylate and metoclopramide compared with oral sumatriptan for migraine. Lancet 1995;346(8980):923. 10. UpToDate. Sumatriptan: drug information lexicomp. Available at: http://www.uptodate. com/contents/sumatriptan-drug-information?source5see_link&utdPopup5true. Accessed March 26, 2014. 11. UpToDate. Dihydroergotamine: drug information lexicomp. Available at: http:// www.uptodate.com/contents/dihydroergotamine-drug-information?source5see_ link&utdPopup5true. Accessed March 26, 2014. 12. UpToDate. Management of migraine headache in children. 2014. Available at: http://www.uptodate.com/contents/management-of-migraine-headache-inchildren?source5search_result&search5migraine1in1children&selectedTitle5 2%7E150#H29. Accessed March 27, 2014. 13. Derosier FJ, Lewis D, Hershey AD, et al. Randomized trial of sumatriptan and naproxen sodium combination in adolescent migraine. Pediatrics 2013;129(6):e1411. 14. Guyuron B, Reed D, Kriegler JS, et al. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg 2009;124(2):461. 15. Schwedt TJ, Demaerschalk BM, Dodick DW. Patent foramen ovale and migraine; a quantitative systematic review. Cephalalgia 2008;28(5):531. 16. UpToDate. Preventive treatment of migraine in adults. 2014. Available at: http://www. uptodate.com/contents/preventive-treatment-of-migraine-in-adults?source5 search_result&search5migraine1prevention&selectedTitle51%7E150. Accessed March 31, 2014.
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