A NEW ERA IN MIGRAINE CARE: CLINICAL ADVANCES WITH RIMEGEPANT, UBROGEPANT, ATOGEPANT, AND ZAVEGEPANT – A NARRATIVE REVIEW

Research objectives: To review and compare the mechanisms of action, clinical efficacy, safety, and unique clinical applications of four gepants - rimegepant, ubrogepant, atogepant, and zavegepant—in the management of migraine. To highlight the advantages of gepants over traditional migraine therapies, especially for patients with cardiovascular risks or medication overuse headache. Methods: Narrative review synthesizing evidence from randomized controlled trials, observational studies, and meta-analyses. Literature search conducted via PubMed and Google Scholar, focusing on studies published between 2023 and 2025. Key findings: Rimegepant is effective for both acute and preventive migraine treatment, with high patient satisfaction and a favorable safety profile. Ubrogepant is approved for acute treatment, showing efficacy particularly when administered early and in patients with cardiovascular contraindications. Atogepant is the first oral gepant approved specifically for migraine prevention, demonstrating significant reductions in monthly migraine days and acute medication use, even in patients unresponsive to other therapies. Zavegepant offers rapid relief via intranasal administration, making it suitable for patients with nausea or vomiting, though it has higher discontinuation rates compared to other gepants. All gepants exhibit generally mild and transient adverse events, with lower discontinuation rates than triptans. Conclusions: Gepants represent a significant advancement in migraine management, providing effective and well-tolerated options for both acute and preventive treatment. Their distinct mechanisms and safety profiles allow for more personalized and safer migraine care, especially in populations unsuitable for older therapies. Future research should focus on direct comparative studies, long-term outcomes, and personalized treatment strategies to further optimize migraine management.