Aspirin, paracetamol (acetaminophen) and caffeine for the treatment of acute migraine attacks: A systemic review and meta-analysis of randomized placebo-controlled trials

Eur J Neurol. 2022 Jan;29(1):350-357. doi: 10.1111/ene.15103. Epub 2021 Sep 28.

Abstract

Background and purpose: Many migraine patients rely on over-the-counter analgesics for the treatment of migraine attacks. Fixed-dose combinations of aspirin, paracetamol and caffeine (APC) have been used for treating migraine in many countries for a long time. We performed a meta-analysis for the comparison of APC versus placebo, which has not been done to date.

Methods: Randomized, blinded, placebo-controlled, parallel-group studies using APC to treat a migraine attack were included in a meta-analysis. We calculated the rate ratio (RRs) associated with APC versus placebo.

Results: Seven studies were included, with 3306 participants (2147 treated with APC and 1159 treated with placebo). For the primary efficacy outcome, being pain-free at 2 h, APC was superior to placebo (19.6% vs. 9.0%, RR 2.2, 95% confidence interval [CI] 1.4-3.3). For the co-primary efficacy outcome, pain relief at 2 h, APC was superior to placebo (54.3% vs. 31.2%, RR 1.7, 95% CI 1.6-1.9). Adverse events were more frequent in the APC than the placebo groups (10.9% vs. 7.8%, RR 1.7, 95% CI 1.3-2.2).

Conclusions: Results showed that APC is superior to placebo in the treatment of acute migraine attacks. Efficacy, measured by pain-free response and pain relief at 2 h, was clinically relevant.

Keywords: OTC; aspirin; caffeine; fixed-dose combination; migraine; paracetamol.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acetaminophen / adverse effects
  • Analgesics, Non-Narcotic* / adverse effects
  • Aspirin / adverse effects
  • Caffeine / adverse effects
  • Humans
  • Migraine Disorders* / drug therapy
  • Randomized Controlled Trials as Topic

Substances

  • Analgesics, Non-Narcotic
  • Acetaminophen
  • Caffeine
  • Aspirin