Abstract

Purpose of reviewTo review 5 new areas in primary headache disorders, especially migraine and cluster headache.Recent findingsCalcitonin gene-related peptide (CGRP) receptor antagonists (gepants—rimegepant and ubrogepant) and serotonin 5-HT1F receptor agonists (ditans—lasmiditan) have completed phase 3 clinical trials and will soon offer novel, effective, well-tolerated nonvasoconstrictor options to treat acute migraine. CGRP preventive treatment is being revolutionized after the licensing of 3 monoclonal antibodies (MABs), erenumab, fremanezumab, and galcanezumab, with eptinezumab to follow, especially designed for migraine; they are effective and well tolerated. For patients seeking a nondrug therapy, neuromodulation approaches, single-pulse transcranial magnetic stimulation, noninvasive vagus nerve stimulation (nVNS), and external trigeminal nerve stimulation, represent licensed, well-tolerated approaches to migraine treatment. For the acute treatment of episodic cluster headache, nVNS is effective, well tolerated, and licensed; nVNS is effective and well tolerated in preventive treatment of cluster headache. The CGRP MAB galcanezumab was effective and well tolerated in a placebo-controlled trial in the preventive treatment of episodic cluster headache. Sphenopalatine ganglion stimulation has been shown to be effective and well tolerated in 2 randomized sham-controlled studies on chronic cluster headache. Understanding the premonitory (prodromal) phase of migraine during which patients experience symptoms such as yawning, tiredness, cognitive dysfunction, and food cravings may help explain apparent migraine triggers in some patients, thus offering better self-management.SummaryHeadache medicine has made remarkable strides, particularly in understanding migraine and cluster headache in the past 5 years. For the most common reason to visit a neurologist, therapeutic advances offer patients reduced disability and neurologists a rewarding, key role in improving the lives of those with migraine and cluster headache.

Highlights

  • Recent findings Calcitonin gene-related peptide (CGRP) receptor antagonists and serotonin 5-HT1F receptor agonists have completed phase 3 clinical trials and will soon offer novel, effective, well-tolerated nonvasoconstrictor options to treat acute migraine

  • Full disclosure form information provided by the author is available with the full text of this article at Neurology.org/cp

  • In pain-free patients, they are just as pain free as they would be on a triptan or a ditan; they may be better off given the tolerability is improved

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Summary

Are gepants potentially disruptive therapies?

There is remarkable consistency in the population effect: about 20% of migraineurs are pain free at 2 hours. The population effect is smaller than triptans, or ditans, where about one-third of migraineurs are pain free at 2 hours. In pain-free patients, they are just as pain free as they would be on a triptan or a ditan; they may be better off given the tolerability is improved. Given the preventive data with the CGRP pathway, both from MABs and gepants used preventively, it seems highly likely that medication overuse will not be a problem since it would seem the more often a gepant is dosed, the less migraine the patient has. Studies on gepants suggest that the dichotomous view of acute therapies vs preventive therapies for migraine is artificial because the CGRP pathway can be engaged for either purpose. Perhaps the most disruptive aspect of this new class is that biologydriven developments can be targeted at the clinical need not constrained as either acute or preventive

CGRP mechanism antagonist
CGRP receptor antibodya
Chronic cluster headache Preventive treatmenta
Licensed Phase III
Conclusion
Findings
FIVE NEW THINGS
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