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Acetaminophen, Aspirin, and Caffeine in Combination Versus Ibuprofen for Acute Migraine: Results From a Multicenter, Double-Blind, Randomized, Parallel-Group, Single-Dose, Placebo-Controlled Study


  • Jerome Goldstein MD,

  • Stephen D. Silberstein MD,

  • Joel R. Saper MD,

  • Robert E. Ryan Jr. MD,

  • Richard B. Lipton MD

  • From the San Francisco Headache Clinic, San Francisco, CA (Dr. Goldstein); Jefferson Headache Center, Philadelphia, PA (Dr. Silberstein); Michigan Head Pain & Neurological Institute, Ann Arbor, MI (Dr. Saper); Ryan Headache Center, Chesterfield, MO (Dr. Ryan); and Department of Neurology, Albert Einstein College of Medicine, Bronx, NY (Dr. Lipton).

Address all correspondence to Dr. Jerome Goldstein, San Francisco Headache Clinic, 909 Hyde Street, Suite 322, San Francisco, CA 94109.


Objective.—Compare the effectiveness of a combination analgesic containing acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of migraine.

Methods.—Multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study. A total of 1555 migraineurs were included in the analysis. No patients were excluded solely because of severity of symptoms or degree of disability. A single 2-tablet dose for each of the 3 treatment groups: a combination product containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or matching placebo. The primary efficacy endpoint was the weighted sum of pain relief (PAR) scores at 2 hours postdose (TOTPAR2) and an important secondary endpoint was the time to onset of meaningful relief.

Results.—There were 669 patients in the AAC group, 666 patients in the IB group, and 220 patients in the placebo group. The 3 treatment groups had similar demographic profiles, migraine histories, and baseline symptom profiles. While both active treatments were significantly better than placebo in relieving the pain and associated symptoms of migraine, AAC was superior to IB for TOTPAR2, as well as for PAR, time to onset of meaningful PAR, pain intensity reduction, headache response, and pain free. The mean TOTPAR2 scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0, respectively (AAC vs. IB, P < .03). The median time to meaningful PAR for AAC was 20 minutes earlier than that of IB (P < .036).

Conclusion.—AAC and IB are safe, cost-effective treatments for migraine; AAC provides significantly superior efficacy and speed of onset compared with IB.