CGRP Inhibitors: The New Standard for Migraine Prevention
Dec, 24 2025
For decades, people with migraine had to make do with drugs meant for other conditions. Antidepressants. Blood pressure pills. Seizure meds. None were designed for migraine. They worked for some, but often came with drowsiness, weight gain, or worse side effects. Then, in 2018, everything changed. The first CGRP inhibitors hit the market - the first migraine-specific preventive drugs ever developed.
What Are CGRP Inhibitors?
CGRP stands for Calcitonin Gene-Related Peptide. It’s a tiny protein in your brain that gets turned on during a migraine attack. When it’s released, it causes inflammation around nerves and makes blood vessels swell - two big reasons why migraines hurt so much. CGRP inhibitors block this protein from doing its damage. There are two main types:- Monoclonal antibodies (mAbs): These are injected shots you get once a month or once every three months. They target either the CGRP protein itself or the receptor it binds to. Brands include Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), and Vyepti (eptinezumab).
- Gepants: These are pills or nasal sprays. They work faster and are used for both stopping an attack and preventing them. Examples: Nurtec ODT (rimegepant), Ubrelvy (ubrogepant), and Zavzpret (zavegepant).
Before CGRP inhibitors, migraine prevention was like using a hammer to fix a watch. Now, we have precision tools made just for the job.
How Effective Are They?
The numbers speak for themselves. In clinical trials, about half of people using CGRP inhibitors cut their migraine days in half. For someone who had eight bad days a month, that drops to four or fewer. Some people go from chronic (15+ days a month) to episodic (under 10 days). A 2022 study compared erenumab to topiramate - a common old-school preventive. The CGRP inhibitor worked nearly twice as well: 41% of users saw a 50%+ reduction, compared to just 24% on topiramate. Real-world results are just as strong. In a survey of over 1,200 migraine patients, 78% said CGRP inhibitors were “very effective” or “effective.” One Reddit user wrote: “Went from 20 migraine days a month to 5 with Aimovig. I can finally plan a weekend.”Who Benefits the Most?
CGRP inhibitors aren’t for everyone - but they’re a game-changer for certain groups:- People with chronic migraine (15+ headache days a month)
- Those who’ve tried at least two other preventives and failed
- Patients with medication overuse headache (taking painkillers too often)
- People with heart disease or high blood pressure - because unlike triptans, CGRP inhibitors don’t constrict blood vessels
- Those who can’t tolerate side effects from older drugs like weight gain, brain fog, or tingling
They’re less helpful if you only get migraines once or twice a month. For those, acute treatments like gepants might be better.
How Are They Taken?
The delivery method matters a lot.Monoclonal antibodies:
- Monthly or quarterly injections under the skin (thigh, stomach, or upper arm)
- Examples: Aimovig (70mg or 140mg monthly), Ajovy (225mg monthly or 675mg every 3 months), Emgality (120mg monthly after a 240mg starter dose)
- Vyepti is an IV infusion done in a clinic every 3 months
Gepants:
- Nurtec ODT: A dissolving tablet taken every other day for prevention, or as needed for an attack
- Ubrelvy: A pill taken at the start of a migraine
- Zavzpret: A nasal spray used for acute treatment
Some people prefer pills over shots. Others don’t mind injections if it means fewer attacks. It’s personal.
Side Effects and Safety
CGRP inhibitors are generally well-tolerated. Most side effects are mild:- Injection site reactions: redness, itching, or pain (about 28% of users)
- Constipation (especially with erenumab)
- Headache (ironically, sometimes the drug causes a mild one at first)
Unlike older drugs, they don’t cause liver damage, kidney issues, or cognitive fog. The FDA requires liver monitoring for ubrogepant and rimegepant, but serious issues are rare.
Long-term safety data beyond five years is still being collected, but so far, no red flags. A 2022 review found only 0.8% of patients stopped treatment due to side effects.
Cost and Insurance
Let’s be honest - these drugs are expensive.- Monoclonal antibodies: $650-$750 per month
- Gepants: $800-$1,000 per month
That’s 3 to 5 times more than generic topiramate or propranolol. But here’s the catch: most U.S. insurance plans cover them - if you jump through hoops.
Insurance denials happen in about 35% of initial requests. You’ll likely need to try and fail on at least two older drugs first. But manufacturers offer support programs: free trials, co-pay cards, and even free medication for those who qualify. Some patients pay $0 out-of-pocket after assistance.
It’s not perfect, but for many, the cost is worth it. One Drugs.com reviewer wrote: “After 15 years of chronic migraine, Emgality got me down to episodic in 3 months. Life-changing.”
How Do They Compare to Old-School Preventives?
| Medication | Type | Effectiveness (≥50% reduction) | Common Side Effects | Cardiovascular Risk |
|---|---|---|---|---|
| CGRP mAbs (e.g., Aimovig) | Injection | ~50% | Injection site reaction, constipation | None |
| CGRP gepants (e.g., Nurtec) | Oral/Nasal | ~45% | Nausea, dizziness | None |
| Topiramate | Oral | ~25% | Brain fog, weight loss, tingling | Low |
| Propranolol | Oral | ~30% | Fatigue, low blood pressure, depression | Caution in asthma/heart block |
| Valproate | Oral | ~35% | Weight gain, hair loss, liver risk | Low |
The biggest win? CGRP inhibitors work even when other drugs failed. In trials, 30% of patients who had tried and given up on two or more preventives still got meaningful relief.
What’s Next?
The field is moving fast. Researchers are testing:- Combining CGRP inhibitors with Botox - early results show even better results
- Nasal and patch versions for easier use
- Use in teens and children - phase 3 trials for adolescents completed in early 2023
- Applications for vestibular migraine and post-head injury headaches
By 2028, biosimilars might lower prices. But for now, the big four mAbs and three gepants are the only options.
Neurologists are already shifting their approach. A 2023 survey found 87% of neurologists now consider CGRP inhibitors a first-line option - no need to fail on other drugs first. That’s a huge change from just five years ago.
Getting Started
If you’re considering CGRP inhibitors:- Track your migraine days for at least a month. Use an app or calendar.
- See a headache specialist or neurologist. Primary care docs are starting to prescribe them, but specialists know the ins and outs.
- Ask about insurance pre-authorization. Most manufacturers have teams that help you navigate this.
- Choose your delivery method - shot or pill - based on your lifestyle.
- Give it 3-4 months to see full effect. These aren’t instant fixes.
Many patients say the hardest part isn’t the injection or the cost - it’s convincing their doctor to take them seriously. If you’ve been told “it’s just a headache,” you’re not alone. But CGRP inhibitors prove migraine is a neurological disease - and it deserves real treatment.
Are CGRP inhibitors safe for long-term use?
So far, yes. The longest data available covers about five years, and no major safety concerns have emerged. The drugs don’t affect the liver, kidneys, or heart in a harmful way. The discontinuation rate due to side effects is under 1%. Long-term studies are still ongoing, but current evidence supports continued use for chronic migraine patients.
Can I use CGRP inhibitors with other migraine meds?
Yes. CGRP inhibitors can be safely combined with acute treatments like triptans, NSAIDs, or gepants. In fact, many patients use a gepant like Nurtec for attacks while taking a monthly CGRP injection for prevention. There are no dangerous interactions reported. Always check with your doctor before mixing medications.
Do CGRP inhibitors cause weight gain or weight loss?
Unlike older preventives like topiramate or valproate, CGRP inhibitors don’t typically cause major weight changes. Some users report mild constipation, which might lead to slight weight loss, but significant weight gain or loss isn’t a common side effect. This makes them a good option for people who’ve had trouble with weight-related side effects from other drugs.
Why are these drugs so expensive?
They’re biologics - complex molecules made using living cells, which are costly to produce. Unlike generic pills, they can’t be easily copied. Patent protections delay cheaper biosimilars until at least 2028. However, most patients don’t pay full price. Manufacturer assistance programs cover 80% or more of out-of-pocket costs for eligible people. Insurance coverage is common after prior authorization.
What if I don’t respond to the first CGRP inhibitor?
You’re not alone. About half of patients respond well, but the other half may need to try a different one. Switching from a monthly injection to a nasal spray, or from one brand to another, often works. Clinical trials show that even patients who failed one CGRP inhibitor can respond to another. Don’t give up after one try - talk to your doctor about alternatives.
Final Thoughts
CGRP inhibitors aren’t a cure. But for the first time in history, people with migraine have a real chance at prevention - without the fog, fatigue, or fear of side effects. They’re not perfect. They’re expensive. Some require shots. But they work where nothing else did.For many, they’ve meant the difference between living in pain and living again. If you’ve struggled with migraines for years, it’s worth a conversation with your doctor. This isn’t just another drug - it’s the start of a new era in migraine care.