The Effectiveness and Tolerability of Oral Acetaminophen/Aspirin/Caffeine (AAC) Combination Regimen as an Acute Treatment for Migraine in Adults: A Meta-Analysis of Randomized Trials

  • Adrian I. Espiritu
  • Huckie C. Del Mundo
  • Jonas Daniel P. Bico
  • Paul Matthew D. Pasco
Keywords: Acetaminophen/Aspirin/Caffeine, migraine without aura, migraine with aura, migraine disorders


Background. Migraine is a highly common disorder that can cause significant disability on an individual, which collectively may lead to a substantial burden for the society. Various expert societies have recommended Acetaminophen/Aspirin/Caffeine (AAC) combination regimen as the first-line drug treatment for migraine attacks; however, there were no pooled evidences summarizing the effectiveness and tolerability of this regimen.

Objective. To determine the effectiveness and tolerability assessment of oral AAC combination regimen as an acute treatment for migraine in adults.

Methods. Relevant studies from inception to March 2014 were searched in Cochrane CENTRAL, MEDLINE, LILACS, Scopus and metaRegister of Controlled Trials. The Cochrane Collaboration’s tool for the assessment of risk of bias was employed. Trials that were randomized, double-blind, parallel-group, placebo and active controlled were included and the data were employed for meta-analysis. To evaluate the quality of evidence, the GRADE approach was utilized for outcomes with sufficient studies and data.

Results. From 225 records identified, 4 trials were included in this review, with a total of 3,608 participants with recorded baseline characteristics. Patient-reported migraine intensity was moderate-severe and the AAC dose used was at 500/500/130 mg. At 2 hours, AAC regimen was statistically different and found to be superior to placebo in terms of pain-free, headache relief, nausea-free, photophobia-free, phonophobia-free and functional disability reduction rates using intension-to-treat analysis. Missing data did not alter the outcome measures generating robust results. Sumatriptan 100 mg was found to be better than AAC in pain-free rate, and phonophobia-free rates at 2 hours. Statistically more patients in the AAC arm experienced “any adverse event” compared to placebo and complaints were commonly nausea and nervousness.

Conclusion. For adult individuals with moderate-severe migraine, a fixed oral dose of Acetaminophen/Aspirin/Caffeine (AAC 500/500/130 mg) may be used as first-line therapy for the acute treatment of migraine and is only associated with mild, infrequent adverse events.


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