Recent research highlights the potential of two new classes of medications, lasmiditan and CGRP antagonists, for the treatment of acute migraines. These therapies provide hope for the millions affected by this debilitating neurological condition, which impacts over 60 million individuals in the United States and approximately 12% of the global population.
According to the Centers for Disease Control and Prevention (CDC), more than 4% of adults reported significant daily interruptions due to migraines in 2021, with women being three times more likely to be diagnosed than men. This disparity is often attributed to hormonal fluctuations. Migraines rank as the sixth highest cause of disability-adjusted life years globally, as reported by the World Health Organization.
The Burden of Migraine
Migraine attacks are characterized by throbbing pain on one side of the head, often accompanied by nausea, vomiting, and heightened sensitivity to sensory stimuli. Approximately one-third of migraine sufferers experience an aura, a visual disturbance preceding the attack. While the exact causes of migraines remain unclear, several pathways, including the trigeminovascular system and neuropeptides like calcitonin gene-related peptide (CGRP), have been implicated in their development.
Pharmacists play a crucial role in managing acute migraine treatment, offering education and ensuring proper medication use. This article focuses on lasmiditan and CGRP antagonists, including atogepant, rimegepant, ubrogepant, and zavegepant, which have emerged as targeted therapies for acute migraine management.
Targeted Treatments: Lasmiditan
Lasmiditan, approved in the United States in 2019, is a first-in-class medication that acts as a selective agonist of the 5-HT 1F receptor. This mechanism allows it to relieve migraine pain without causing vasoconstriction. Clinical trials, including the SAMURAI and SPARTAN studies, demonstrated its effectiveness compared to placebo, with significant pain relief reported by patients within two hours of administration.
The SAMURAI trial involved 2,231 adult participants, while the SPARTAN trial included 2,869 adults with a history of disabling migraines. Both studies found that lasmiditan significantly increased the number of patients reporting freedom from pain. Common side effects of lasmiditan include dizziness, somnolence, and paresthesia, but it is generally well tolerated. Due to its potential for causing central nervous system depression, patients are advised to avoid driving or operating heavy machinery for at least eight hours after taking the medication.
CGRP Antagonists: Rimegepant, Ubrogepant, and Zavegepant
CGRP antagonists are another promising class of medications designed to block the migraine-triggering effects of CGRP. Rimegepant, ubrogepant, and zavegepant are oral formulations that target acute migraines and have shown positive results in clinical trials. The phase 3 ACHIEVE I and II trials evaluated ubrogepant in over 3,300 adults, demonstrating significant improvements in pain relief and reduction of migraine symptoms compared to placebo.
Rimegepant was tested in two multicenter trials, showing notable efficacy in relieving pain and associated symptoms within two hours of administration. Similarly, zavegepant has demonstrated effectiveness in treating acute migraines, with studies indicating favorable safety profiles and mild side effects such as nausea and fatigue.
While CGRP antagonists do not cross the blood-brain barrier as readily, they have been generally well tolerated by patients. A meta-analysis suggests that the number needed to treat (NNT) for CGRP antagonists ranges from 8 to 14, indicating they are effective in acute migraine management. In comparison, traditional oral triptans have an NNT of 3 to 11.
Despite these advancements, pharmacists and healthcare providers must consider individual patient factors, including comorbidities and potential drug interactions, when recommending treatments. Lasmiditan’s potential for misuse and the emergence of rare side effects, such as Raynaud’s phenomenon, also warrant careful monitoring.
The approval and availability of lasmiditan and CGRP antagonists mark a significant development in the management of acute migraines, offering new options for patients who have not responded well to traditional therapies. As the understanding of migraine mechanisms evolves, the role of innovative treatments continues to expand, providing hope for improved quality of life for those affected by this condition.
