clinical topic updates

Current Progress and Future Directions in Migraine

by David W. Dodick, MD


Monoclonal antibodies (mAbs) that target calcitonin gene-related peptide (CGRP) are among the most recently introduced therapies for migraine prevention. Our featured expert discusses the rationale for the use of these agents.

Expert Commentary

David W. Dodick, MD

Professor, Department of Neurology
Director, Concussion Program
Director, Headache Program
Mayo Clinic
Scottsdale, AZ

We have made tremendous inroads recently in developing the first available migraine-specific preventive treatments.”

David W. Dodick, MD

We have made tremendous inroads recently in developing the first available migraine-specific preventive treatments. We have never actually had a preventive treatment designed and developed specifically for migraine until now. There are 4 biologics (mAbs) that have been developed that target CGRP, which is a protein or neuropeptide found within the trigeminal sensory system, peripherally, and throughout the brain. Based on a variety of different preclinical animal models and human studies dating back to decades ago, it became evident that CGRP was a high-value target for the prevention of migraine and, indeed, for the acute treatment of migraine. We now have several acute treatments that target CGRP as well (ie, the gepants, which are oral CGRP receptor antagonists).

So, we have come a long way in that regard. And we have expanded the therapeutic armamentarium to treat patients with acute migraine. For the past 3 decades, we have had triptans, which are excellent medications, but not everybody responds. In fact, roughly 30% to 40% of patients do not actually respond to triptans. Another proportion have contraindications to their use, particularly cardiovascular-related contraindications, and yet another proportion of patients do not tolerate the medications at all.

We have gained experience with these compounds, and some of the clinical trials that were conducted early on have now been following patients for more than 5 years and have not reported any serious adverse events or complications. We have not closed the book on it, though, and, in the real world, we do see side effects that are not observed in clinical trials; however, this is generally what we expect to see. By and large, they appear to be very safe. Now, anti-CGRP mAbs tend to remain in the body for several months. They must be used with caution in women who plan to become pregnant; these patients are advised to stop taking the drugs for at least 5 months prior to becoming pregnant to allow for clearance of the antibodies. It is also true that these agents are not effective for everyone. Some patients respond well, while others respond partially or not at all.

Looking to the future, there are a number of potential avenues to explore. For example, pituitary adenylate cyclase-activating peptide is another neuropeptide that has been found at increased levels during a migraine attack, and there are several reasons to believe that it may be another high-value target.


Bohm PE, Stancampiano FF, Rozen TD. Migraine headache: updates and future developments. Mayo Clin Proc. 2018;93(11):1648-1653. doi:10.1016/j.mayocp.2018.09.006

Hargreaves R, Olesen J. Calcitonin gene-related peptide modulators - the history and renaissance of a new migraine drug class. Headache. 2019;59(6):951-970. doi:10.1111/head.13510

Lombard L, Farrar M, Ye W, et al. A global real-world assessment of the impact on health-related quality of life and work productivity of migraine in patients with insufficient versus good response to triptan medication. J Headache Pain. 2020;21(1):41. doi:10.1186/s10194-020-01110-9

Puledda F, Messina R, Goadsby PJ. An update on migraine: current understanding and future directions. J Neurol. 2017;264(9):2031-2039. doi:10.1007/s00415-017-8434-y

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