Comparative efficacy of AAC and ibuprofen versus lasmiditan, ubrogepant, and rimegepant for the acute treatment of episodic migraine in adults: a systematic review and network meta-analysis
Abstract
Background: A range of pharmacologic options is available for acute migraine treatment, yet the efficacy and safety of commonly used over-the-counter (OTC) therapies relative to newer prescription agents remain unclear. Given the scarcity of direct head-to-head trials, this network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluated selected OTC therapies against newer oral agents, including CGRP antagonists and the 5-HT1F receptor agonist.
Methods: A comprehensive literature search was conducted in PubMed, Embase, and CENTRAL for RCTs of acute migraine therapies published between January 1990 and July 2025. Primary outcomes were 2-h (2 h) pain relief and pain freedom; secondary outcomes included 2-h photophobia, phonophobia and nausea. Effect sizes were calculated as relative risks (RRs) with 95% confidence intervals (CIs). A frequentist NMA was conducted to estimate comparative efficacy and safety across the treatment network.
Results: This NMA synthesized evidence from 25 RCTs, including 5 different interventions across 19 dose categories, involving a total of 22,100 participants with migraine. Compared with placebo, acetaminophen, aspirin, and caffeine (AAC) combination showed superior 2 h pain relief (RR, 1.76; 95% CI, 1.61-1.94; p-score = 0.96), followed by ibuprofen 400 mg and 200 mg. For 2 h pain freedom, AAC, ibuprofen 400 mg, and lasmiditan 200 mg showed broadly comparable favorable effects versus placebo, with similar RRs and p-scores. AAC also…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 22,100 participants or records.
Read the paper
Related studies
- Calcium Ions in the Physiology and Pathology of the Central Nervous System
- AI-powered in silico twins: redefining precision medicine through simulation, personalization, and predictive healthcare
- In silico functional, structural and pathogenicity analysis of missense single nucleotide polymorphisms in human MCM6 gene
- In Silico drug repurposing pipeline using deep learning and structure based approaches in epilepsy
- Targeting serotonin receptors with phytochemicals – an in-silico study
- In silico exploration of anti-prostate cancer compounds from differential expressed genes
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.