SynthesisFrontiers in neurology2026
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.
Synthesis in Frontiers in neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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-HT 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 produced the greatest reductions in photophobia and phonophobia at 2 h (photophobia: RR, 1.99; 95% CI, 1.62-2.45; p-score = 0.97; phonophobia: RR, 1.53; 95% CI, 1.28-1.84; p-score = 0.89), while ibuprofen Liquigel 400 mg provided additional meaningful benefit. For nausea, rimegepant 75 mg demonstrated the strongest effect (RR, 1.15; 95% CI, 1.08-1.22; p-score = 0.85), followed by ibuprofen Liquigel 400 mg and AAC. Conclusion: In this NMA, OTC therapies showed meaningful efficacy and favorable safety for acute episodic migraine versus placebo, with ibuprofen and AAC demonstrating consistent benefits across 2 h pain and secondary outcomes. These findings support their use as effective, accessible options alongside newer oral agents. Larger trials and patient-level analyses are needed to refine efficacy, optimize dosing, and personalize migraine management. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261325571, Identifier CRD420261325571.
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