CGRP Inhibitors for Migraines: What You Need to Know

For the millions of people that experience migraines, effective treatment can be hard to find. Calcitonin gene-related peptide inhibitors, or CGRP inhibitors, may provide hope. CGRP inhibitors are the first medications designed to target, prevent, and treat migraines in adults.

CRGP inhibitors reduce the number and severity of headaches for many migraine patients with few side effects. This article will explain the role of CGRP in migraines and how the latest treatments may be able to help.

What are migraines?

Migraines are a debilitating type of headache characterized by long-lasting, throbbing head pain. Individuals with migraines are often sensitive to light, sound,

and strong odors. Migraines can be expensive to treat. They can cost patients over eight thousand dollars each year on outpatient and emergency room visits.1

How many people experience migraines each year in the US?

Approximately 15% of Americans experience migraines on a regular basis. Women are two times as likely to experience migraines versus men. 1,2 Migraines are a common condition in the general population.

What are the symptoms of a migraine?

Migraines differ from other types of headaches in both symptoms and duration. Many migraine patients report nausea alongside sensitivity to light, sound, and smell during a migraine attack. The time span of a migraine attack may last from hours to days. 2 In between attacks, many people living with migraines may be symptom-free. Some may report minor pain or brain fog.

A third of patients report experiencing a warning before the headache starts. These warning signs, or auras, occur before the head pain begins. Auras vary from fatigue to visual changes like flashing lights or blind spots.

What Causes a Migraine?

While the cause of migraines is uncertain, the American Migraine Foundation states they often start with a trigger. These triggers can vary by person. Some common triggers include stress, hormone fluctuations, medication overuse, or lack of sleep.3

What is the role of CGRP in migraines?

CGRP is a protein that plays a normal role in the body by healing wounds and regulating blood flow to the organs of the body. However, too much CGRP can cause a migraine attack.4

The nervous system, especially the trigeminal nerve, becomes sensitive during a migraine. The trigeminal nerve releases CGRP. This causes dilates the blood vessels in the thin tissue layers that covers and protects the brain. High

levels of CGRP can lead to the throbbing pain experienced by individuals during a migraine. Too much CGRP can also cause inflammation.1,2

Treatments

The latest treatments for migraines are CGRP inhibitors. They differ from older treatments by targeting the protein or the receptors it binds to.2,4 Most of these medications prevent migraines, but treat migraines when they occur. Patients can inject themselves at home or the doctor’s office, take a pill, or receive an intravenous injection (IV).

Studies indicate the injectable CGRP inhibitors initiate improvements in at least 50% of patients after the first dose.4 For those taking the pill form, relief can be as quick as 2 hours after the onset of a headache.5

Check out these CGRP inhibitors currently on the market:

Aimovig

How is it taken?: monthly via injection

How does it work?: blocks the CGRP receptor

How is it used?: prevention

Side effects: upper respiratory infections, urinary tract infections, fatigue and pain and redness at the injection site.2

Ajovy

How is it taken?: monthly or every 3 months by injection

How does it work?: targets the protein

How is it used?: prevention

Side effects: constipation, pain and redness at injection site, allergic reaction.6

Emgality

How is it taken?: monthly by injection

How does it work?: targets the protein

How is it used?: prevention

Side effects: fatigue, dry mouth, pain and redness at injection site, allergic reaction.6

Nurtec

How is it taken?: Pill

How does it work?: targets the CGRP receptor

How is it used?: prevention and treatment of active migraine

Side effects: nausea, allergic reaction.1

Qulipta

How is it taken?: Pill

How does it work?: targets the protein

How is it used?: prevention

Side effects: constipation, nausea, fatigue, elevated liver enzymes.1

Vyepti

How is it taken?: IV every 3 months at the doctor’s office

How does it work?: targets the protein

How is it used?: prevention

Side effects: fatigue, nausea, allergic reactions and nasal problems. 7

CGRP inhibitors have few serious side effects, but they’re not recommended for everyone. They may not be right for pregnant people or those at high risk for stroke or heart attack. They are currently not approved for patients younger than 18 years old. There needs to be more research on this population. Some CGRP medications might be riskier for patients with kidney, liver, or cardiovascular disease.

Summary

Migraines are a debilitating health problem that affects many Americans. CGRP inhibitors are the first medications designed to target, prevent, and treat migraines in adults. They have improved the quality of life for many migraine patients by reducing the number and duration of migraine attacks.

There are some considerations for people with heart or kidney disease. Allergic reactions should also be monitored with this class of medications, however most patients report mild side effects. Your doctor can help you decide if one of these medications would be right for you.

References

1. Rissardo JP, Caprara ALF. Gepants for Acute and Preventive Migraine Treatment: A Narrative Review. Brain Sci. 2022;12(12):1612. Published 2022 Nov 24. doi:10.3390/brainsci12121612.

2. Mohanty D, Lippmann S. CGRP Inhibitors for Migraine. Innov Clin Neurosci. 2020;17(4-6):39-40.

3. Top 10 migraine triggers and how to deal with them: AMF. American Migraine Foundation. July 27, 2017. Accessed May 14, 2023. https://americanmigrainefoundation.org/resource-library/top-10-migraine-triggers/.

4. Deen M, Correnti E, Kamm K, et al. Blocking CGRP in migraine patients - a review of pros and cons. J Headache Pain. 2017;18(1):96. Published 2017 Sep 25. doi:10.1186/s10194-017-0807-1

5. Lipton RB, Croop R, Stock EG, et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. N Engl J Med. 2019;381(2):142-149. doi:10.1056/NEJMoa1811090

6. Nissan GR, Kim R, Cohen JM, Seminerio MJ, Krasenbaum LJ, Carr K, Martin V. Reducing the Burden of Migraine: Safety and Efficacy of CGRP Pathway-Targeted Preventive Treatments. Journal of Clinical Medicine. 2022; 11(15):4359. https://doi.org/10.3390/jcm11154359

7. Smith, T.R., Spierings, E.L.H., Cady, R. et al. Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials. J Headache Pain 22, 16 (2021). https://doi.org/10.1186/s10194-021-01227-5