Pharmacologic Treatment of Acute Attacks of Episodic Migraine: A Systematic Review and Network Meta-analysis for the American College of Physicians

Background: Migraine is common, affecting 15% of Americans. Purpose: To compare benefits and harms of pharmacologic treatments for acute attacks of episodic migraine in adults and assess cost-effectiveness. Data Sources: Three electronic databases searched to October 2024, gray literature, and reference lists. Study Selection: Two investigators independently selected English-language randomized trials. Data Extraction: Single reviewer data extraction with second review. Dual independent risk of bias and certainty of evidence (COE) assessment. Data Synthesis: Twenty-one head-to-head and 165 placebo-controlled trials were included in meta-analyses and network meta-analyses. Triptans were more effective than acetaminophen (low COE) and nonsteroidal anti-inflammatory drugs (NSAIDs) (high COE) for pain outcomes at 2 hours and pain freedom up to 48 hours. Triptan and acetaminophen combinations were more effective than acetaminophen alone (moderate COE) for pain outcomes at 2 hours and pain freedom up to 48 hours but not more than triptans alone (low COE). Triptan and NSAID combinations were more effective for pain outcomes at 2 hours and pain freedom up to 48 hours compared with acetaminophen (low COE), gepants (low COE), NSAIDs (high COE), and triptan monotherapy (moderate COE). Triptan regimens, however, often had a higher risk for adverse events. One study found triptans more cost-effective than ditans and gepants. Limitations: Harms assessment was limited to randomized trials. Many comparisons lacked sufficient evidence to draw conclusions. Conclusion: Triptans and combinations of triptans were more effective than NSAID and acetaminophen alone.