For decades, migraine prevention meant borrowing drugs designed for blood pressure, epilepsy or depression. That has changed. There is now a whole class of medicines built specifically for migraine, and in 2024 the American Headache Society recognised them as a first-line option for prevention.
Key takeaways
- CGRP-targeting therapies (antibodies and gepants) are now a first-line choice for migraine prevention.
- Gepants treat attacks without constricting blood vessels, an option for some people who cannot take triptans.
- Botox remains a proven prevention for chronic migraine and can be combined with CGRP therapy.
- Using acute medicine too often can make headaches worse ("medication-overuse headache").
What is CGRP and why does it matter?
Calcitonin gene-related peptide (CGRP) is a signalling molecule released by the trigeminal nerve during a migraine attack. Its levels rise during attacks, and giving CGRP can trigger migraine in people who are prone to it. Blocking CGRP, or its receptor, reduces migraine days for many patients, often with fewer side effects than older preventives.
1. CGRP monoclonal antibodies (preventive)
These are given as a monthly or quarterly self-injection, or as an IV infusion every three months:
- Erenumab: blocks the CGRP receptor, monthly injection
- Fremanezumab: monthly or quarterly injection
- Galcanezumab: monthly injection, also approved for episodic cluster headache in some markets
- Eptinezumab: IV infusion every 12 weeks
Most patients can judge whether it's working within about three months. Constipation is a notable side effect, particularly with erenumab.
2. Gepants (oral CGRP receptor blockers)
- Ubrogepant: for acute attacks
- Rimegepant: for acute attacks, and every other day for prevention
- Atogepant: daily tablet for preventing episodic and chronic migraine
- Zavegepant: nasal spray for acute attacks
Gepants do not narrow blood vessels, which makes them useful for some people with cardiovascular risk factors who can't take triptans. Early research also suggests they don't cause medication-overuse headache the way triptans and painkillers can.
3. Ditans
Lasmiditan targets the 5-HT1F receptor and also avoids vasoconstriction. It can cause dizziness and drowsiness, so patients must not drive for 8 hours after a dose.
4. Neuromodulation devices
Drug-free options include remote electrical neuromodulation worn on the upper arm, external trigeminal nerve stimulation, non-invasive vagus nerve stimulation and single-pulse transcranial magnetic stimulation. They suit patients who want to avoid medication, including during pregnancy planning (always discuss this with your doctor).
5. Botox for chronic migraine
For people with headache on 15 or more days per month, onabotulinumtoxinA (the PREEMPT protocol) remains one of the best-studied treatments. It is 31 small injections every 12 weeks. Real-world studies suggest some patients benefit further from combining Botox with a CGRP antibody. Read our Botox for migraine guide →
How do we choose?
In the headache clinic, Dr. Agha weighs your attack frequency, previous treatments, other medical conditions, pregnancy plans, cost and access in Lebanon or the US, and your own preference for tablets, injections or devices. Keeping a headache diary for four weeks before your visit makes this much more precise.
Beyond medication
Regular sleep, meals and hydration, aerobic exercise, limiting acute medicine to fewer than 10 days a month, and identifying triggers such as fasting, poor sleep, stress, alcohol and hormonal changes all remain the foundation of care.
Sources
- Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey A; American Headache Society. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update. Headache. 2024;64(4):333–341.
- Ailani J, Burch RC, Robbins MS. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021–1039.
- Ailani J, et al. Atogepant for the preventive treatment of migraine. N Engl J Med. 2021;385:695–706.
- Croop R, et al. Oral rimegepant for preventive treatment of migraine. Lancet. 2021;397:51–60.
- Dodick DW, et al. OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT pooled results. Headache. 2010;50:921–936.
American board-certified neurologist with subspecialty expertise in clinical neurophysiology. More than 10 years of practice in Chicago and Beirut. Sees patients in Beirut, Beverly Hills and Upland.
This article is educational and is not a substitute for a medical consultation.