Calcitonin gene-related peptide (CGRP) inhibitors are prescription medications used to treat and prevent migraine attacks. They can help treat chronic migraine.
CGRP inhibitors are relatively new drugs that were first approved by the FDA in 2018. CGRP inhibitors have transformed the landscape for migraine treatment. They work as well as other medications but have fewer side effects. With this type of treatment, some people have even cut their number of headache days by more than 75%. In other words, CGRP inhibitors can help people live better with less trouble from migraine attacks.
CGRP inhibitors were designed to target the CGRP protein. This protein can fuel pain and inflammation during a migraine attack. CGRP inhibitors block this protein to prevent migraine attacks from happening. In the same way, they can ease pain and other symptoms during migraine attacks.
There are two different types of CGRP inhibitors:
CGRP monoclonal antibodies. Used for migraine prevention, these are taken as infusions using an IV at your doctor’s office or as injections that you can take at home.
Gepants. Mostly used to treat acute migraine attacks, they are available as pills that you take by mouth and as nasal sprays. But there are a couple of varieties of CGRP receptor antagonists that can also be used for migraine prevention.
What Are the Benefits of CGRPs for Migraine?
CGRP inhibitors are the first medication designed specifically for migraine prevention.
“CGRP inhibitors are typically better tolerated than other medications while offering similar efficacy,” says Hope O’Brien, MD, a neurologist at The Christ Hospital Health Network in Kenwood, Ohio.
Some of the other benefits of CGRP inhibitors include:
- Resulting in fewer migraine attacks
- Preventing some migraine attacks completely
- Making certain migraine attacks shorter and less painful
“They also work faster than some of the older, nonspecific medications,” says O’Brien, who’s also a professor at the University of Cincinnati College of Medicine and Morehouse School of Medicine. “Patients can expect to see improvement, in some cases, as early as one week, compared to waiting six to eight weeks for some relief.”
If you’re considering getting pregnant, it’s easier and quicker to stop taking CGRP inhibitors so you can safely transition into a stage where you’re trying to get pregnant, O’Brien says. There’s also less concern about medication overuse, which can lead to more headaches.
How do CGRPs compare to other migraine preventatives?
Earlier, the go-to options for migraine attacks were all medications originally meant to treat other conditions. These include antidepressants, blood pressure medication, and anti-seizure drugs. While these medications can help prevent migraine attacks, they often come with side effects, including dizziness and nausea.
“In the past, our migraine preventative treatments were not targeted and were found by chance — older drugs made for blood pressure, epilepsy, and depression that were noted to improve migraines,” says Kate Kennedy, an advanced registered nurse practitioner and specialist in neurology at Overlake Medical Center and Clinics in Bellevue, Washington. “These older drugs often have significant side effects, and patients were less likely to take them because of this.”
Because CGRP inhibitors were specifically designed to target migraine attacks, not only do they come with fewer side effects, but they’re also better tolerated.
There haven’t been many head-to-head studies comparing CGRPs with other migraine treatment options. But one study found that over half of the people who took the CGRP inhibitor erenumab (Aimovig) saw more than a 50% decline in migraine attacks. That was compared to a 31% reduction for people taking topiramate (Topamax). And nearly 9 in 10 people taking the CGRP medication were able to stay on it because it was so easily tolerated, while nearly 4 in 10 people taking topiramate had to stop because the side effects were too harsh.
Another study showed that taking the CGRP monoclonal antibody helped more people cut the number of their monthly headache days and improve their quality of life compared with Botox.
What Are the Risks of CGRPs?
When CGRPs first came out, doctors were concerned about potential risks that were not seen in the studies because CGRP plays a role in many different bodily functions.
“Seven years later, our fears do not seem to have come to reality,” says Kennedy.
But more research is needed to know exactly how CGRPs can affect people in the long term.
The main risks of CGRP inhibitors include:
- Pain, bleeding, redness, and swelling at the injection site
- Constipation
- Hair loss (alopecia)
- Muscle spasms
- Fatigue
- Throat irritation
- Nausea
- Raynaud’s disease
- High blood pressure
“Overall, there are few risks associated with CGRP inhibitors, especially compared to other medications,” says O’Brien.
The most common risks are constipation and nausea, but O’Brien says she only sees them in around 5% of people taking them. If you have a history of high blood pressure, talk with your doctor before taking CGRP inhibitors. And if you have a higher risk of high blood pressure, you should watch your blood pressure while taking this medication. If you have Raynaud’s disease, stay out of the cold to help manage potential Raynaud’s symptoms.
Are there long-term side effects of taking CGRPs for migraine?
Because CGRP inhibitors have only been around since 2018, there is limited research and data available about the long-term use of CGRP inhibitors. We need more research to know how this medication works long-term.
How do these risks compare to other migraine preventatives?
CGRPs may be a better option for you than other drugs used to prevent migraine.
“The older drugs are much more likely to cause side effects,” says Kennedy. “They work well for some patients, but not as many patients will be able to tolerate them and see benefits.”
Many drugs used to prevent migraines come with side effects that are difficult to manage, including nausea and dizziness. Because they come with challenging side effects, many people find it hard to stick with these medications. On the other hand, since CGRP inhibitors are better tolerated, more people are able to take them for a longer period of time.
Who Might Be a Good Candidate for CGRP Inhibitors?
CGRP inhibitors are an effective way to treat and prevent migraine attacks with few side effects. If you have chronic migraine, talk to your doctor about trying CGRP inhibitors.
“I think anyone with migraine is a good candidate for CGRP inhibitors,” says O’Brien. “The tolerability, safety profile, side effects profile, and quick response rate make CGRP inhibitors a really strong option for treating migraine attacks.”
Who should avoid CGRPs?
If you have constipation or a latex allergy, certain CGRP monoclonal antibodies, such as erenumab (Aimovig), may not be the best fit for you. You may also want to avoid this specific medication if you have high blood pressure.
“If you had an unusual or severe side effect to one CGRP antagonist, I would be hesitant to try another in the same class,” says Kennedy.
Not enough data is available on the use of CGRP inhibitors during pregnancy. You should talk to your doctor if you’re on CGRP monoclonal antibodies and thinking about getting pregnant in the next year or so. Many doctors recommend stopping CGRP monoclonal antibodies five to six months before trying to get pregnant. There also isn’t much data on the safety of breastfeeding while taking CGRP inhibitors.
Because CGRP inhibitors can react with certain medications, you may need to make adjustments or avoid certain CGRP inhibitors if you’re taking certain antibiotics, cancer treatments, HIV medications, or nirmatrelvir or ritonavir (Paxlovid).
If you have end-stage liver or renal disease, you may need to avoid CGRP inhibitors and should talk to your doctor about the best option for you.
You may also need to consider the cost and insurance issues related to CGRP inhibitors. CGRP inhibitors can cost a lot more than older medications, and insurance companies often make you try other treatments before they approve the use of CGRPs. And even with approval, CGRP inhibitors can come with costly copays.
How to Decide if CGRPs Are Right for You
CGRP inhibitors are an exciting addition to migraine treatments. For many people, they have resulted in fewer and milder migraine attacks with fewer side effects. If you are living with chronic migraine, CGRP inhibitors may help you better manage migraine attacks and improve your quality of life.
If you’re interested in exploring CGRP inhibitors, talk to your doctor. If you do try CGRP inhibitors, you should regularly check in with your health care provider about whether it’s working. To gauge if it’s a good fit for you, your doctor may consider things like whether it:
- Lowers your number of headache days
- Results in fewer and less severe migraine attacks
- Improves your ability to function in day-to-day life
- Helps you manage migraine-related stress
If one CGRP inhibitor doesn’t work for you, you may be able to switch to another to see if it’s a better fit. Some people also combine different CGRP inhibitors or combine CGRP inhibitors with nonspecific migraine medications.
While many people get great results from CGRP inhibitors, there are still questions about the long-term use of these medications. And CGRP inhibitors have not been studied enough in certain populations, including pregnant or breastfeeding people, adults over 65, and children. You should also talk with your doctor if you have certain conditions like high blood pressure, end-stage liver disease, or Raynaud’s disease.
You may also need to consider the financial realities of taking CGRP inhibitors. While CGRP inhibitors are now considered a standard treatment for migraine attacks, they are not always covered by insurance and can come with pricey copays.
No migraine treatment will work for everyone, so it’s important that you talk with your doctor about finding the best option for you.
