CGRP Migraine Medications: What You Need To Know

Migraine is a complex neurological condition affecting millions of people worldwide. For those living with migraine, the advent of new medications specifically designed to target the mechanisms behind migraine attacks has been a beacon of hope. Among these groundbreaking treatments are medications that focus on the calcitonin gene-related peptide (CGRP), a key player in migraine pathology.

** While Migraine Strong writes about the latest in migraine treatments, this is not medical advice. We are patient educators and all information you read should be discussed with your doctor.

Preparing for this article, we had an informative Instagram Live interview with Dr. Eric Baron who is a headache specialist at the Cleveland Clinic in Cleveland, Ohio. Dr. Baron has a wonderful website that includes a headache symptom checker, education center which describes different headache disorders and a blog that he regularly updates. You can also find him on Instagram and Tiktok where he posts fantastic videos about migraine and headache disorders.

Understanding CGRP and Its Role in Migraine

CGRP is a protein found in the brain and nervous system that is involved in transmitting pain signals. During a migraine attack, CGRP levels increase, leading to inflammation and the dilation of blood vessels, which contribute to the pain and other symptoms experienced during a migraine attack. CGRP medications work by blocking the CGRP protein or its receptor, thereby preventing these pain signals from triggering migraine symptoms. (1)

Preventive CGRP Medications

Preventive medications are designed to reduce the frequency, severity, and duration of migraine attacks. Several CGRP-targeting preventive medications have been approved for use (1):

1. Aimovig (Erenumab): Administered as a monthly injection, Aimovig blocks the CGRP receptor, preventing the protein from attaching and triggering migraine attacks.
2. Ajovy (Fremanezumab): Ajovy offers flexible dosing schedules, with options for monthly or quarterly injections. This flexibility allows patients and their healthcare providers to tailor the treatment to individual needs.
3. Emgality (Galcanezumab): Like Aimovig, Emgality is a monthly injection that targets the CGRP protein, reducing the frequency of migraine attacks.
4. Vyepti (Eptinezumab): Unique among CGRP medications, Vyepti is administered via a 30-minute intravenous infusion every three months. This quarterly dosing can be a convenient option for those who prefer fewer treatments.
5. Qulipta (Atogepant): Qulipta stands out as an oral preventive medication. Taken daily in pill form, it offers an alternative to those who may be uncomfortable with injections or infusions.

Acute CGRP Medications

Acute medications are taken at the onset of a migraine attack to alleviate symptoms. The introduction of CGRP antagonists for acute treatment has provided new options for those who need immediate relief. (1) These medications are also not associated with rebound headache or medication adaptation headache.

1. Ubrelvy (Ubrogepant): This oral tablet is taken at the first sign of a migraine attack. By blocking the CGRP receptor, Ubrelvy can effectively reduce pain and other symptoms associated with migraine.
2. Nurtec ODT (Rimegepant): Nurtec is a versatile medication available as an orally disintegrating tablet. It can be used both as an acute treatment and as a preventive measure when taken every other day. This dual functionality makes Nurtec a valuable tool for managing migraine.
3. Zavzpret (Zavegepant): Zavzpret is administered as a nasal spray, providing a quick and convenient option for those who experience nausea or difficulty swallowing during a migraine attack. It is fast-acting, making it a reliable choice for acute treatment.

How CGRP Medications Work

CGRP medications work by targeting either the CGRP protein itself or its receptor (2). By blocking these pathways, the medications prevent the cascade of events that lead to migraine symptoms. Here’s a closer look at how they function:

• CGRP Protein Inhibitors: Medications like Emgality, Ajovy and Vyepti target the CGRP protein (ligand) directly. By binding to the protein, they prevent it from interacting with its receptor, thus stopping the pain signals from being transmitted.
• CGRP Receptor Antagonists: Aimovig, Ubrelvy, Nurtec, Qulipta and Zavzpret block the receptor that CGRP would normally bind to. This blockade prevents the receptor from activating and triggering a migraine attack.

Administration and Dosage

The administration and dosage of CGRP medications vary, offering options to fit different lifestyles and preferences (1):

• Monthly Injections: Aimovig, Emgality, and the monthly option of Ajovy fall into this category. These injections are typically self-administered, making them convenient for home use.
• Quarterly Injections and Infusions: The quarterly option of Ajovy and the infusion treatment Vyepti are administered less frequently, which can be advantageous for those looking to reduce the frequency of their treatments.
• Daily Pills: Qulipta represents the daily pill option for preventive treatment, offering ease of use for those who prefer oral medication.
• Acute Treatments: Ubrelvy, Nurtec, and Zavzpret are taken at the onset of a migraine attack, providing quick relief. Ubrelvy and Nurtec are oral tablets, while Zavzpret is a nasal spray.

Common complaints about the CGRP injectables is that they hurt or burn when injected. One option to remedy this complaint is to inject in the belly area. I know this sounds very scary, but I have found it to be much less painful overall! Others have suggested icing the area prior to administering the injection and removing the medication from the refrigerator and allowing it to warm up for several hours. 

Benefits and Considerations

CGRP medications have revolutionized migraine treatment, providing new options for both prevention and acute management. (1) However, like all medications, they come with benefits and considerations:

Benefits:

• Targeted Treatment: CGRP medications specifically target the pathways involved in migraine attacks, offering effective relief and prevention.
• Flexible Administration: With various administration methods and dosing schedules, patients can choose the option that best fits their lifestyle.
• Reduced Frequency of Attacks: Many patients report a significant reduction in the frequency and severity of their migraine attacks with regular use of preventive CGRP medications.

Considerations:

• Side Effects: Common side effects may include constipation, fatigue and injection site reactions. If a rash appears at the injection site, Benadryl (diphenhydramine) may be used to treat it. If the rash is more widespread, discontinuation of the medication may be necessary. It’s important to bring these reactions to your doctor’s attention. Other side effects sometimes reported in the migraine community includes nausea, worsening reflux and hair loss.
• Cost and Insurance: CGRP medications can be expensive, and insurance coverage may vary. Patients should check with their insurance provider and explore patient assistance programs if needed. The savings available through the patient assistance programs are not available for Medicare and other government insurances. This is due to the Anti-Kickback Statute which is explained in detail at this link.
• Individual Response: Not all patients will respond to CGRP medications in the same way. It may take some time to find the most effective treatment and dosage. If one CGRP medication is not effective, it is reasonable to try another medication that has a different mechanism of action. For example, changing from a protein inhibitor to a receptor antagonist or vice versa. Layering other migraine preventives and acute medications from different categories can also lead to better outcomes. Read our article about some medications that can make migraine worse.
• Pregnancy and trying to conceive: It is currently recommended to discontinue injectable medications five months prior to trying to conceive due to their long half life. If taking an oral medication, discontinuing the medication when pregnancy is confirmed is recommended. Check with your doctors to confirm that these are still the recommendations as this information is frequently updated based on safety profile studies. (3)

Conclusion

CGRP medications have opened new doors in the treatment of migraine, offering hope and relief to many who suffer from this debilitating condition. Whether used as a preventive measure or for acute treatment, these medications provide targeted, effective options for managing migraine. If you are considering CGRP medications, consult with your healthcare provider to determine the best course of action for your individual needs. With the right treatment plan, living with migraine can become more manageable, allowing you to regain control over your life.

If you have tried any of the new CGRP medications let us know in the comments or in our closed Facebook group.

References:
1. https://www.ncbi.nlm.nih.gov/books/NBK560648/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413335/
3. https://journals.sagepub.com/doi/10.1177/03331024231158083
4. Migraine Strong Instagram Live with Dr. Eric Baron, Headache Specialist, Cleveland Clinic, Ohio