Peter Goadsby, MBBS, provides a historical perspective on the evolution of clinical management, and therapies for preventive and acute chronic migraine.
Peter Goadsby, MBBS
PUBLISHED November 06, 2018
Peter Goadsby, MBBS: Migraine management is usually considered in 2 big piles. The first pile is lifestyle advice: someone advises a patient to have regular sleep, regular meals, regular exercise—a regularity of things—and then we discuss treatments, namely 2 broad concepts: acute treatment and preventive treatment. The evolution of acute treatment has been the evolution from relatively nonspecific things that are useful in pain generally—aspirin, acetaminophen, nonsteroidals like naproxen and ibuprofen, the so-called triptans, serotonin 5-HT1B and 1D receptor agonists that were developed in the late 1980s and then first marketed in the 1990s. What we’re seeing at the moment is the continued evolution of these treatments.
As we’ve moved away from the idea that you have to constrict blood vessels, which is wrong, it turns out that all you have to do is turn off those nerve pathways. New medicines are being developed, and what we’re seeing is phase III studies for 2 classes: the 5-HT1F—receptor agonist and ditans—specifically lasmiditan—which turns off trigeminal pathways and doesn’t have a vessel effect; it is also clearly effective in the acute treatment of migraine. Another group of treatments: the gepants, calcitonin gene-related peptide CGRP, and small-molecule receptor antagonists that have no vasoconstrictive effect. Two of them, rimegepant and ubrogepant, are both effective as acute treatments of migraine.
We’re moving away from nonspecific treatments to medicines that are designed for migraine where we understand the pathways; they’re effective and well tolerated. We haven’t done prevention yet; that is going to be next. On the preventive side, what we’ve had forever—as long as I’ve been practicing—is a ragtag collection of treatments from various areas. Specifically propranolol, a blood pressure beta blocker or candesartan; topiramate, from the epilepsy class; and amitriptyline, from the tricyclic class, which is an antidepressant that is also effective as a migraine treatment. For the first time, we have a class of specific migraine preventives, the CGRP: calcitonin gene-related peptide pathway monoclonal antibodies.
As we’ve seen developments in preventive acute therapies, the next level of progression is a hybrid or quantum level of thinking. We know that CGRP—pathway blockades from monoclonal antibodies are derived from a new medicine called atogepant in phase II, which is a small molecule receptor antagonist whose pathway could be used as a preventive. We know, from the acute-therapy studies with gepants, rimegepant, and ubrogepant—that they, as well, can be used acutely. What we suddenly come to is a CGRP pathway that works in both acute and preventive therapy. This is really going to change the conversation and comprehension about treatment since it is no longer sensible to say that a patient can only receive a preventive or acute therapy. How we leverage that going forward and how that changes the conversation clinically is going to be exciting in the next short period of development.