A Randomized, Placebo-controlled Trial of Acetaminophen for Treatment of Migraine Headache

Mary Jane Prior, PhD, MPH; Joseph R. Codispoti, MD; Min Fu, MS


Headache. 2010;50(5):819-833. 

In This Article

Abstract and Introduction


Objective.—To evaluate the efficacy and safety of acetaminophen 1000 mg for the treatment of episodic migraine headache.
Background.—While acetaminophen is commonly used to treat migraine, there have been limited published clinical trial efficacy results.
Design/Methods.—Ten investigators at 13 private, ambulatory, primary care sites in the United States enrolled and treated 346 outpatient adults 18–72 years of age with migraine headache of moderate to severe intensity into a randomized, placebo-controlled, double-blind clinical trial of 6 hours duration. Each patient was randomly assigned to a single dose of study medication of acetaminophen 1000 mg (n = 177) or placebo (n = 169). The percentage of patients with a reduction in baseline headache pain intensity from severe or moderate to mild or none 2 hours after treatment and the headache pain intensity difference from baseline at 2 hours were the primary efficacy measures. Other measures of pain relief, severity differences from baseline for migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability, and percentage of patients with migraine-associated symptoms reduced to none were also assessed.
Results.—Significantly (P = .001) more patients treated with acetaminophen 1000 mg reported mild to no pain after 2 hours (52.0%) compared with those treated with placebo (32.0%). The mean pain intensity difference from baseline measured at 2 hours was significantly (P < .001) greater for patients treated with acetaminophen 1000 mg (0.82) compared with those treated with placebo (0.46). A significant difference in favor of acetaminophen 1000 mg over placebo was also observed at 1 hour after treatment for the percentage of patients with mild to no pain and for mean pain intensity difference from baseline. Acetaminophen 1000 mg was significantly more effective than placebo for all but 1 (pain reduced to none at 2 hours) clinically important secondary pain relief outcomes. Mean severity changes from baseline in migraine-associated symptoms of nausea, photophobia, phonophobia, and functional disability at 2 and 6 hours were significantly (P < .001) in favor of acetaminophen over placebo; the percentage of patients with no symptoms at 2 and 6 hours statistically significantly favored acetaminophen in 6 of 8 comparisons. Adverse events, overall, and specifically for nausea, were reported more frequently in the placebo group.
Conclusions.—Acetaminophen 1000 mg, a nonprescription drug, is an effective and well-tolerated treatment for episodic and moderate migraine headache. In addition, acetaminophen generally provided a beneficial effect on associated symptoms of migraine including nausea, photophobia, phonophobia, and functional disability.


Migraine is a common disabling primary headache disorder consisting of periodic episodes of painful headache sometimes preceded by aura and frequently accompanied by 1 or more of the following symptoms: nausea, photophobia, and phonophobia.[1] Based on a national survey (American Migraine Study II) conducted in 1999 that included results from 13,869 households, migraine occurs frequently and recurrently in the United States with an estimated 28 million sufferers 12 years of age and older.[2] Based on the American Migraine Prevalence and Prevention Study (AMPP), a national survey conducted in 2004 that included 162,576 participants, 17.1% of women and 5.6% of men have 1 or more migraines per year, and 77% of migraineurs report 1 or more migraines per month.[3] The social and economic impact of migraine is considerable, resulting in days missed from work or school and interference with family and social activities. Functional impairment has been reported to occur in over 90% of migraineurs, ranging from some impairment (39%) to severe impairment/required bed rest (53%).[2] Fifty-one percent of 29,727 migraineurs reported that work/school productivity was reduced by at least 50% during the previous 3 months.[2] In addition, 31% reported missing at least 1 day of work/school in the previous 3 months.[2] A study of families that included a migraineur indicated increased use by an employed parent of short-term disability days (5 per year), sick days (4 per year), and workman's compensation days (3 per year) when compared with employed parents of matched control nonmigraine families.[4] The annual national direct cost associated with migraine in the United States has been estimated as $11 billion (2004 data) and the indirect cost as $12 billion (2002–03 data).[5,6]

Use of nonprescription analgesics for the treatment of acute migraine is common. The AMPP indicated that 49% of migraineurs usually used only nonprescription drugs to treat migraine headaches, and that an additional 29% of migraineurs sometimes used nonprescription drugs and sometimes used prescription drugs to treat their migraines.[3] Results of an earlier United States national survey (American Migraine Study II) indicated that 57% of migraineurs used only nonprescription drugs to treat their headaches.[7] Randomized controlled trials have demonstrated a beneficial treatment effect for migraine headache for nonprescription drugs including acetaminophen,[8–10] ibuprofen,[11–13] and the combination of acetaminophen, aspirin, and caffeine.[9,13,14] Despite published data to the contrary, some treatment recommendations indicate that insufficient data exist to recommend the use of acetaminophen for migraine headache treatment.

Acetaminophen is an effective, well-tolerated analgesic that has been available as a nonprescription medication for over 50 years. Acetaminophen is a nonopiate, centrally acting analgesic and antipyretic agent derived from para-aminophenol. Acetaminophen is approved for use for the temporary relief of minor aches and pains associated with the common cold, headache, toothache, muscular aches, backache, for the minor pain of arthritis, for the pain of menstrual cramps, and for the reduction of fever. Current acetaminophen labeling in the United States directs consumers to take 1000 mg every 4 to 6 hours while symptoms last. Consumers are also directed not to take more than 8 tablets in 24 hours and not to use for more than 10 days unless directed by a doctor.

The current study was designed to compare the efficacy and safety of acetaminophen 1000 mg to placebo in treating moderate-to-severe episodic migraine headache.


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