Objective: To review and highlight current literature on emerging acute migraine treatments, focusing on CGRP receptor antagonists, gepants, and 5-HT receptor agonists (ditans).
Background: Current acute migraine therapy consists of nonspecific analgesia and triptans. Limitations to these medicines, including lack of efficacy in many patients, side effects and the contraindication of triptans in patients with cardiovascular disease, suggest that there is an unmet need for new treatments. Studies of serotonin pharmacology led to the development of triptans, 5-HT receptor agonists, some of which have actions at the 5-HT receptor. Exploration of the role of calcitonin gene-related peptide (CGRP) has resulted in the development of CGRP receptor antagonists.
Method: The authors performed a literature search of Pubmed and Cochrane databases as well as reviewed abstracts presented at meetings: American Headache Society, American Academy of Neurology, European Headache Federation and the Migraine Trust International Symposium, as well as on-line sources. The authors briefly detail the relevant migraine pathophysiology pertaining to 5-HT receptor and the CGRP pathway relevant to acute therapies. Recent clinical trials of acute therapies in which 5-HT receptor agonists or CGRP receptor antagonists were studied are summarized.
Results: Two 5-HT receptor agonists have reached phase II clinical trials. One, lasmiditan, has completed 2 phase III clinical trials, demonstrating a significant effect for pain freedom and most bothersome symptom at 2 hours. Among the 6 gepants tested for the acute treatment of migraine to date, after issues for some of hepatic safety or efficacy, 2 CGRP receptor antagonists, rimegepant and ubrogepant, have completed phase III trials showing efficacy and safety.
Conclusion: Current available therapies have either been nonspecific or had important limitations, including in patients with cardiovascular risk factors. Phase III clinical trials of lasmiditan, rimegepant and ubrogepant all met their primary endpoints, so the options for migraine-targeted acute therapy will likely soon increase.
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