| Summary: | Purpose: Current acute migraine treatment consists of migraine-specific agents, namely triptans, as well as non-specific analgesia, such as non-steroidal anti-inflammatory drugs and acetaminophen (paracetamol). Both have tolerability issues, or are not indicated, or both, in many patients; they may also lead to medication overuse headache. We aimed to review the available evidence supporting the use of migraine-specific acute, and possibly preventive, small molecules targeting the CGRP receptor, their mechanism of action, pharmacology and data from available clinical trials. Methods: We performed a literature search of the PubMed and Cochrane databases in March 2020, using the keywords: “CGRP receptor antagonists”, “gepants”, “CGRP receptor blockers” and “CGRP acute medication”. In total, 24 published studies were included. Results: The development of first generation gepants was stopped either because of hepatic safety issues or for commercial reasons. Second generation gepants reviewed here are rimegepant, ubrogepant, atogepant and vazegepant. Rimegepant and ubrogepant have shown positive results as acute treatments leading to FDA approval. Rimegepant and atogepant have positive results as preventive treatments, with the latter being developed only for this indication. Vazegepant, with positive preliminary data, would be the first intranasal acute treatment gepant. Vascular diseases are not a contraindication to gepants and the available evidence suggests these drugs would not lead to medication overuse headache. Conclusion: Positive efficacy, safety and tolerability data has been reported for all gepants currently in clinical use or development. They offer an entirely novel class of treatment for migraine.
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