At least 39 million people in the United States experience the debilitating type of headache known as migraine, according to the American Migraine Foundation. But very few medications and therapies have been designed with the prevention of migraine in mind.
Instead, most of the existing migraine treatments have some other intended purpose that just happens to help people with migraine, too. Anti-epilepsy drugs, like topiramate (Topamax), or the antidepressants and blood pressure medications often prescribed to people with migraine, can lessen your number of headache days. But that’s not what they were made to do.
Thankfully, that’s no longer the case. Advances in the use of monoclonal antibodies have helped researchers develop ways to target painful migraine episodes right at their source.
Monoclonal antibodies are used as a form of immunotherapy to treat some diseases. But for migraine, they work in a different way that doesn’t involve the immune system.
Here’s everything you need to know about the exciting ways monoclonal antibodies work to prevent migraine headaches. We’ll also discuss several recently approved drugs that might, at last, give you some long-awaited migraine relief.
How is this helpful for migraine? These antibodies can target and block a specific type of protein called calcitonin gene-related peptide, or CGRP. Researchers have found CGRP to be one of the major sources of migraine pain.
During a migraine attack, CGRP is often released in the nerve cells of the brain. This causes the blood vessels to widen and certain parts of your brain to become inflamed. Experts like the American Migraine Foundation believe the CGRP response causes the physical pain of a migraine episode for most people.
Using monoclonal antibodies to reduce the effects of CGRP can lead to fewer episodes of migraine pain.
This is what the new generation of migraine drugs is designed to do. As antagonists to CGRP, they can prevent it from connecting with pain receptors and causing many of the physical symptoms of migraine.
Are monoclonal antibodies a form of immunotherapy?
Immunotherapy treatments involve engaging your immune system, either by suppressing it or boosting it, to help your body fight disease and infection. Doctors often use monoclonal antibodies as a form of immunotherapy, particularly in treating:
- cancer
- organ transplant rejection
- allergies
- rheumatoid arthritis
- inflammatory bowel disease
But monoclonal antibodies are used in a different way to treat migraine. It’s important to know that these drugs do not work on your immune system. Instead, they target CGRP.
- For episodic migraine with fewer than 15 migraine days per month, people taking monoclonal antibodies had 1 to 2 fewer migraine days compared to placebo.
- For chronic migraine with 15 or more migraine days per month, they had 2 to 2.5 fewer migraine days compared to placebo.
Another way of looking at how effective these drugs are is to see how many people experience substantial improvement with use. One
But how do these drugs compare with more traditional migraine prevention treatments? Here are some stats about how well three common preventive treatments work for migraine.
- Blood pressure medications. Beta-blockers such as propranolol and timolol are often prescribed for migraine prevention, though different medications have different results. Propranolol is usually considered the most effective treatment. One
2019 review suggests it can reduce episodic migraine by 1 to 2 headaches per month and chronic migraine by up to 50 percent. - Antidepressants. Tricyclic antidepressants are typically prescribed for migraine prevention, though a
2017 review shows that other types such as selective serotonin reuptake inhibitors may be just as effective. That same review also suggests tricyclic antidepressants can reduce migraine days by up to 50 percent. - Anti-epilepsy drugs. Doctors commonly prescribe topiramate (Topamax) as a preventive medication. According to 2014 research, it seems to also have around a 50 percent rate for decreasing headache days.
Let’s look at the four injectable medications approved by the Food and Drug Administration (FDA) for migraine.
Erenumab (Aimovig)
Aimovig was
Like the other injectable drugs, Aimovig is a preventive medication, not an abortive one. That means it can lessen the number and severity of migraine headaches you get, but won’t treat a headache already in process or relieve migraine symptoms on the spot.
Aimovig is injected either by you or a caregiver once per month into the thigh, upper arm, or stomach. Most people only inject 1 dose per month, but some may need or be approved for 2 doses per month.
Fremanezumab (Ajovy)
Ajovy is injected under the skin and blocks CGRP proteins from functioning. It’s a preventive, not an abortive medication.
The main difference between Ajovy and other injectables is that Ajovy can be long acting, so you have a choice when it comes to dosing. You can inject 1 dose per month or opt for a quarterly schedule, injecting 3 separate doses once every 3 months.
Galcanezumab (Emgality)
Emgality is another injectable, though it may be more likely to cause side effects than the others. It’s a preventive injection taken once per month in the thigh, abdomen, buttock, or the back of your upper arm.
Emgality is slightly different in that your first dose is called a loading dose. This means you take double the amount of Emgality the first time and then move down to the standard dose the following month.
Eptinezumab (Vyepti)
Vyepti works the same way as the other three injectables in terms of mechanism. It binds to CGRP proteins and blocks them from causing a nerve response. It’s also a preventive medication, not an abortive one.
But Vyepti isn’t an injectable. It’s an intravenous (IV) infusion given every 3 months at your doctor’s office. It takes about 30 minutes to receive the full dose of the medication. Most people take a 100-milligram dose of Vyepti, but some people need a 300-milligram dose.
The side effects of most monoclonal antibodies for migraine are the same. There are minor differences among them, but in general, doctors consider them to be equally safe. These drugs also tend to not have any listed interactions with other prescription drugs, making them easy to combine with other migraine therapies.
Common side effects
According to Migraine Canada, clinical studies found that possible side effects include:
- constipation
- injection site pain
- muscle pain
- joint pain
Meanwhile, in actual clinical settings, additional side effects were noted. These are the effects your doctor’s office might report on if they have patients taking these drugs. They include:
There is also the potential for allergic reactions in some people. Let your doctor know if you have a history of allergies to medications.
One
Cardiovascular side effects
Experts are still discussing the effects of anti-CGRP drugs on heart health. CGRP widens blood vessels, and these drugs block that process. There are concerns that this could lead to hypertension or even a ministroke.
But a 2020 review found no evidence that anti-CGRP drugs have a negative effect on the heart. People with a history of cardiovascular problems don’t seem to be at an increased risk when taking these drugs.
Side effects of other drugs used to treat migraine
The potential side effects of a relatively new class of drugs can be intimidating. But it’s important to remember that traditional migraine treatments, which are similar in effectiveness to anti-CGRP drugs, also have side effects.
| Drug type | Side effects |
|---|---|
| beta-blockers | • fatigue • dizziness • poor circulation • gastrointestinal (GI) distress |
| tricyclic antidepressants | • increased headache • GI distress • dizziness • fatigue • weight gain |
| anti-epilepsy drugs | • memory loss • brain fog • fatigue • mood changes • nausea • increased risk of kidney stones, according to |
In general, the majority of people can safely use monoclonal antibodies for migraine. Your doctor will consider your whole medical history before deciding whether this treatment is right for you.
Monoclonal antibodies are an effective way of preventing migraine, but researchers are looking into other possible treatments.
Gepants
Gepants are also anti-CGRP therapies. They block CGRP at the pain receptors, but are not injectable or IV drugs.
They are usually taken orally, either as pills or dissolvable tablets, so they work faster and don’t stay in your system as long. This allows them to be used as abortive medications, stopping symptoms of a migraine, as well as preventives.
The first gepant was approved by the FDA in
- ubrogepant (Ubrelvy)
- rimegepant (Nurtec ODT)
Only Nurtec ODT is approved for both preventive and abortive use.
In general, gepants are tolerated well and cause few side effects, according to
Clinical trials
As of 2022, several current clinical trials in various phases are looking into new pathways to prevent migraine. Areas of interest include:
- pituitary adenylate cyclase-activating polypeptide type 1 receptor inhibitors, which block a protein that triggers migraine pain
- ditans, which are currently used for acute treatment but not prevention
- orexin receptor inhibitors, which block pathways in the hypothalamus of the brain
- kallikrein blockers, which lower the production of a protein that releases CGRP
- ketamine, which targets glutamate and serotonin — chemicals that may contribute to migraine pain
Learn more about clinical trials for migraine prevention.
Unlike the migraine treatments of the past — which were designed to treat other medical conditions — monoclonal antibodies target migraine pain directly at the source. They:
- are
as effective as, if not more effective than, traditional migraine prevention therapies - do not interact with many other prescription drugs
- are relatively easy to self-administer
While they come with a risk of some mild side effects, monoclonal antibodies for migraine are largely safe for many people to use, and the benefits often outweigh the risks.