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Am Fam Physician. 2002;65(9):1871-1873

Question Addressed

  • What are the effects of drug treatments for acute migraine headache?

BeneficialLikely to be beneficialTo be covered in future issues of Clinical Evidence
Salicylates (L-acetylsalicylate alone or in combination with metoclopramide; aspirin combination with acetaminophen and caffeine)
Tolfenamic acid
Ergotamine derivatives
Effects of nondrug treatments for migraine headache
Effects of prophylactic treatments for migraine headache
DefinitionMigraine is a primary headache disorder manifesting as recurring attacks, usually lasting for four to 72 hours, and involving pain of moderate to severe intensity, often accompanied by nausea, and sometimes vomiting, and/or sensitivity to light, sound, and other sensory stimuli. The 1988 International Headache Society (IHS) criteria (see accompanying table listing the IHS criteria) include separate criteria for migraine with and without aura.1
Incidence/PrevalenceMigraine is common worldwide. Prevalence has been reported to be between 5 and 25 percent in women and 2 and 10 percent in men. Overall, the highest incidence for migraine without aura has been reported between 10 and 11 years of age at 10 per 1,000 person-years. The peak incidence of migraine without aura in boys is between 10 and 11 years of age (10 per 1,000 person-years) and in girls between 14 and 17 years of age (19 per 1,000 person-years). The incidence of migraine with aura peaks in boys around five years of age (seven per 1,000 person-years) and in girls around 12 to 13 years of age (14 per 1,000 person-years).2
Etiology/Risk FactorsData arising from independent representative samples from Canada,3,4 the United States,5,6 several countries in Latin America,7 several countries in Europe,811 Hong Kong,12 and Japan13 demonstrate a female-to-male predominance and a peak in middle-aged women. Migraine risk has been reported to be 50 percent more likely in people with a family history of migraine.14
PrognosisAcute migraine is self limited and only rarely results in permanent neurologic complications. Chronic recurrent migraine may cause disability through pain, and may affect daily functioning and quality of life. Female prevalence of migraine with or without aura has a declining trend after 45 to 50 years of age.
Clinical AimsTo reduce frequency of migraine, intensity of accompanying symptoms, and duration of headache, with minimal adverse effects.
Clinical OutcomesHeadache relief or being pain free at different times after medication. Pain relief at specific post-dose times. In this review, headache relief is reported at two hours unless expressed otherwise. Some randomized controlled trials (RCTs) include the need for rescue medication and headache recurrence as outcome measures.

Drug Treatments


Five RCTs have found that aspirin (900 mg orally, 1,000 to 1,620 mg of oral lysine acetylsalicylate [L-ASA], or intravenous L-ASA) alone or in combination with 10 mg of metoclopramide, increases the proportion of people with headache relief compared with placebo. One RCT found no significant difference between L-ASA and oral sumatriptan. Another RCT found that L-ASA was less effective than subcutaneous sumatriptan in relieving acute migraine pain. One RCT found that a nonprescription combination (acetylsalicylic acid plus acetaminophen plus caffeine) in nondisabling migraine was superior to placebo in relieving acute pain in migraine. Two RCTs found increased headache relief with effervescent aspirin in combination with metoclopramide or alone versus placebo. In one subsequent RCT, aspirin efficacy was not significantly different to an acetaminophen plus codeine combination, although both were superior to placebo in acute migraine pain relief.


Three RCTs found that diclofenac versus placebo significantly improved headache relief. One RCT found that more people taking intramuscular diclofenac versus intramuscular acetaminophen had partial relief of migraine symptoms


Four RCTs found limited evidence that ibuprofen versus placebo improved headache relief.


One crossover RCT found limited evidence that naproxen versus placebo reduced headache intensity. Three RCTs comparing naproxen with ergotamine found that naproxen significantly reduced migraine intensity.


One RCT found limited evidence that tolfenamic acid versus placebo increased the number of people with pain relief, and no difference was found between tolfenamic acid and sumatriptan. One RCT found no significant difference between tolfenamic acid and acetaminophen in migraine symptoms. One crossover RCT found that tolfenamic acid, alone or in combination with metoclopramide or caffeine, versus placebo reduced headache intensity.


One systematic review has found that ergotamine derivatives provide better relief of acute migraine than placebo. One RCT found that ergotamine plus caffeine versus sumatriptan was less effective for headache relief or reducing the need for rescue medication. One RCT of ergotamine versus ergotamine plus metoclopramide found no difference in headache intensity. One systematic review has found worsening of baseline nausea and vomiting with ergotamine compared with placebo.


One systematic review and one subsequent RCT have found that eletriptan versus placebo increases headache relief. The subsequent RCT found that eletriptan versus sumatriptan significantly increased headache relief.


Three RCTs have found that naratriptan versus placebo increases headache relief at four hours. One RCT comparing naratriptan with sumatriptan found no significant difference in headache recurrence.


One systematic review has found that rizatriptan versus placebo significantly improves headache relief. Two RCTs found no significant difference between rizatriptan and sumatriptan.


One systematic review has found that subcutaneous, oral, or intranasal sumatriptan versus placebo increases headache relief.


Large RCTs have found that oral zolmitriptan versus placebo increases headache relief and is as effective as sumatriptan for the treatment of acute pain in migraine.

Migraine without aura (common migraine)
It is defined as five or more headache attacks lasting for four to 72 hours with accompanying symptoms of nausea/vomiting and/or phonophobia and photophobia. Pain should comply with at least two of the following characteristics: (1) unilateral; (2) throbbing; (3) moderate to severe intensity; and (4) increases with physical activity.
Migraine with aura (classic migraine)
Two or more headache attacks are required that comply with three of the following characteristics: (1) one or more fully reversible aura symptoms indicating focal cerebral cortical or brainstem dysfunction; (2) at least one aura symptom developing gradually over more than four minutes, or two or more symptoms occurring in succession; (3) no aura symptom should last more than one hour; and (4) headache follows aura with a pain free interval of less than 60 minutes.
In migraine with and without aura, secondary causes of headache should be excluded; if any structural damage is found, it should not explain headache characteristics. Less stringent criteria for migraine without aura can be used. In clinical practice, the so-called borderline migraine can be diagnosed when one of the above criteria is not met.

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