Migraine is a prevalent and debilitating primary headache disorder with significant socio-economic and personal impacts. This study aims to evaluate the safety and efficacy of zavegepant, a recently approved third-generation small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray (BHV-3500), ), to be administered as a nasal spray in the acute treatment of migraine attacks. A search was conducted across multiple databases, to identify relevant randomized clinical trials (RCTs). After the study selection process, 2 RCTs (involving 2850 participants) and an additional trial for qualitative synthesis were included for analysis. The primary efficacy outcome assessed was freedom from pain at 2 hours post-dose, which showed a significantly higher likelihood in the zavegepant 10 mg group compared to the placebo group (RR 1.54, 95% CI 1.28 to 1.84). Additionally, zavegepant 10 mg demonstrated superior freedom from the most bothersome symptoms (MBS) at 2 hours post-dose compared to placebo (RR 1.26, 95% CI 1.13 to 1.42). Safety outcomes were evaluated based on adverse events (AEs), with the zavegepant 10 mg group experiencing a higher incidence of AEs compared to placebo (RR 1.78, 95% CI 1.5 to 2.12). Dysgeusia was the most commonly reported AE in the zavegepant group (RR 4.18, 95% CI 3.05 to 5.72). zavegepant effectively relieved pain and bothersome symptoms at 2 hours post-dose, however, it was associated with a higher incidence of adverse events, predominantly dysgeusia. In conclusion, while further research and clinical trials are needed to evaluate the long-term effectiveness and safety of zavegepant in diverse patient populations, the analyzed trials provide compelling evidence that zavegepant is a potentially effective acute treatment for migraine.
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