CGRP receptor antagonists (gepants) and anti-CGRP monoclonal antibodies have revolutionized both acute and preventive migraine treatment, with proven efficacy and good tolerability.
First migraine-specific preventivesCGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) are the first preventive treatments ever designed specifically for migraine rather than repurposed from other conditions
What the researchers found
The review covers five advances in primary headache disorders:
1. CGRP receptor antagonists (gepants): Rimegepant and ubrogepant completed Phase 3 trials for acute migraine, offering effective non-vasoconstrictor alternatives to triptans
2. CGRP monoclonal antibodies for prevention: Three licensed (erenumab, fremanezumab, galcanezumab) with eptinezumab to follow — the first migraine-specific preventive treatments, effective and well tolerated
3. Neuromodulation: Transcranial magnetic stimulation, noninvasive vagus nerve stimulation (nVNS), and external trigeminal nerve stimulation licensed for migraine
4. Cluster headache advances: nVNS effective for acute and preventive treatment; galcanezumab effective for episodic cluster headache prevention in a controlled trial
5. Premonitory phase understanding: Recognizing prodromal symptoms may help explain apparent migraine triggers and improve self-management
Why it matters
Migraine is the most common reason to visit a neurologist, affecting over 1 billion people globally. Before CGRP-targeting therapies, migraine treatments were all repurposed from other conditions (blood pressure drugs, antidepressants, seizure medications). The CGRP revolution represents the first time treatments were designed specifically for migraine based on understanding the underlying peptide biology.
How the study worked
This is a clinical review by Peter Goadsby (a leading headache researcher) summarizing five key developments in primary headache disorders, focusing on clinical trial results and newly licensed therapies.
What this study cannot tell us
Written in 2019, this review captured the field at a transitional moment. Long-term safety data for CGRP-targeting therapies was still limited. Cost and access issues were not addressed. The review focuses mainly on episodic migraine and cluster headache, with less coverage of chronic migraine subtypes.
How to read the evidence
This is a clinical review by a leading authority summarizing Phase 3 trial results and licensed therapies. The individual therapies discussed have strong clinical trial evidence supporting their use.
When this study was published
Published in 2019, this review captured the CGRP therapy revolution as it was unfolding. Since then, additional gepants, antibodies, and indications have been approved, confirming the trends described.
The bigger picture
The CGRP story is one of the great translational successes in peptide medicine. From the discovery that CGRP levels rise during migraine attacks to the development of targeted antibodies and small molecule antagonists, this peptide-based approach has fundamentally transformed a field that had been stagnant for decades — and may extend to cluster headache and other pain conditions.
Questions still open
- What are the long-term effects of chronic CGRP blockade on other physiological processes where CGRP plays a role?
- Can CGRP-targeting therapies be combined with neuromodulation for enhanced migraine prevention?
- Will gepants eventually replace triptans as first-line acute migraine treatment?
Common questions
What is CGRP and why is it important for migraines?
What's the difference between gepants and CGRP antibodies for migraine?
Read the original research
Primary headache disorders: Five new things.
Neurology. Clinical practice, 9(3), 233-240
Citation
Goadsby, Peter J. (2019). Primary headache disorders: Five new things.. Neurology. Clinical practice, 9(3), 233-240. https://doi.org/10.1212/CPJ.0000000000000654