CGRP Injections for Migraine: How Effective Are They Really?

CGRP injections are a newer class of migraine prevention drug that, for a lot of people, actually work. In the large trials that brought them to market, patients with frequent migraines saw their monthly headache days drop by about half, with fewer side effects than older preventives like topiramate or propranolol. They are not magic, and they are not right for everyone, but they have changed what most headache specialists reach for first.

This explainer walks through what CGRP is, how the injections work, what the trials actually showed, and how they compare to older prevention options. It draws on peer-reviewed research from three headache specialists listed in the Convene directory, including the neurologist who co-discovered CGRP's role in migraine and researchers who have shaped how modern headache medicine thinks about prevention.

What is CGRP, and why does it matter for migraine?

CGRP stands for calcitonin gene-related peptide. It is a small signaling molecule that the nerves around your brain release during a migraine attack. In 1990, a study in Annals of Neurology measured blood from the veins that drain the head during migraine attacks and found that CGRP levels spiked, which was one of the first pieces of evidence that this peptide was doing something real in migraine, not just sitting in the background [3]. A 2017 review in Physiological Reviews laid out how that signal fits into the bigger picture of migraine as a disorder of how the brain processes sensory input [2].

The practical takeaway is simple. If you block CGRP or the place where CGRP docks onto nerve cells, you can interrupt the chain of events that leads to a migraine. A small 2004 trial in the New England Journal of Medicine showed that an early experimental CGRP-blocking drug called BIBN 4096 could stop a migraine attack that was already underway, which was the first real proof that this approach worked in people [4]. That finding opened the door to the injectable preventives that are now in wide use.

How do the injections work?

The current CGRP preventives are monoclonal antibodies. These are lab-made proteins that stick to either CGRP itself or the receptor it uses, so the signal never lands. There are four on the market in the United States:

• Erenumab (Aimovig), given as a monthly injection you can do at home with a small pen-style device. It targets the CGRP receptor.
• Fremanezumab (Ajovy), monthly or quarterly, targets CGRP itself.
• Galcanezumab (Emgality), monthly, targets CGRP itself.
• Eptinezumab (Vyepti), given as a quarterly infusion in a clinic, targets CGRP itself.

Three of the four are injections you learn to give yourself at home, like an insulin pen. The injection goes into the fat under the skin of your belly or thigh, takes a few seconds, and most people describe it as a quick sting. You do not have to take a daily pill, which is a big part of why patients and doctors like these drugs.

At a glance

What the landmark trials actually showed

The trial that put CGRP blockers on the map was the STRIVE study of erenumab, published in the New England Journal of Medicine in 2017. STRIVE enrolled patients with episodic migraine, meaning they had migraines but fewer than 15 headache days a month, averaging about 8 migraine days per month at the start. After six months on erenumab, their monthly migraine days dropped by about 3 to 4, and nearly half of patients had their migraine frequency cut in half or better. The side effect rate was very close to placebo [1]. Later trials of the other CGRP antibodies (fremanezumab, galcanezumab, and eptinezumab) replicated similar benefit across both episodic and chronic migraine populations, which is why all four are now standard options in most headache clinics.

The picture these trials paint is this. CGRP injections are not a cure. On average, they cut migraine days roughly in half for about half of the people who try them. But because the side effect profile is gentle, the people who respond can stay on treatment for a long time without the trade-offs that made older preventives hard to tolerate.

How do they compare to older preventives like topiramate and propranolol?

Before CGRP antibodies existed, the go-to preventives were drugs that were designed for something else entirely. Topiramate was an epilepsy drug. Propranolol was a blood pressure drug. Both were found, somewhat by accident, to reduce migraine frequency. A 2004 trial in Archives of Neurology showed that topiramate at 100 mg per day cut monthly migraine frequency by about 2 days more than placebo in a double-blind study [5]. That was considered a strong result at the time, and topiramate became a first-line option in the American Academy of Neurology's practice guideline for migraine prevention [7].

Here is the catch. Older preventives work, but they also come with side effects that many patients cannot live with. Topiramate can cause word-finding trouble, tingling in the hands and feet, weight loss, and kidney stones. Propranolol can cause fatigue, cold hands, low blood pressure, and sometimes low mood. A 2009 review in Neurologic Clinics summarized what headache specialists had been seeing for years: the efficacy of older preventives was real, but adherence was poor because of how they made patients feel [6].

CGRP injections changed that math. You get migraine prevention that works about as well as topiramate for many patients, without the cognitive side effects. For someone whose job depends on being able to think clearly, or who has already tried a pill that made them feel foggy, that is a meaningful difference.

Who benefits most?

The 2007 American Migraine Prevalence and Prevention study, published in Neurology, found that more than one in four people with migraine are candidates for preventive therapy, but most of them never get it. The paper made the case that preventive treatment is under-used in the United States [8]. That is part of why CGRP injections got so much attention. They gave doctors a new tool to offer the large group of patients who had either failed older preventives or been afraid to try them.

In practice, insurance in the United States generally asks you to try at least one or two older preventives before it will cover a CGRP injection. That means the people who end up on a CGRP drug are often people who already had a rough time with topiramate, propranolol, or amitriptyline. The research backs up using CGRP treatment in that group. A 2019 review in Neurologic Clinics walks through the treatment ladder and how newer therapies fit into it [9], and a 2021 Lancet review on migraine epidemiology and systems of care lays out why access to preventive treatment is still a problem even with better drugs available [10].

There is also a related issue that matters for who should be on any preventive. A 2008 longitudinal study in the journal Headache looked at how episodic migraine turns into chronic migraine over time, and found that overusing certain acute medications, especially barbiturates and opioids, increased the risk that migraine would progress from occasional to constant [11]. If you are taking a lot of pain pills to cope with frequent migraines, that is an important reason to talk to a doctor about a prevention plan. CGRP injections can sometimes be the first preventive that actually lets a patient cut back on their acute rescue medications.

What to ask your doctor

• How many migraine days do I have per month, and does that put me in the episodic or chronic category?
• Have I tried enough older preventives for my insurance to cover a CGRP injection? If not, which ones are worth trying first?
• Am I using acute migraine medications often enough that I might be at risk for medication overuse headache?
• If we try a CGRP injection, how will we know it is working, and how long should I give it before deciding?
• Are there reasons I should not be on a CGRP blocker, like heart disease, pregnancy, or a history of constipation?
• What does the shot actually cost me with my insurance, and is there a manufacturer copay program I can use?

The bottom line

CGRP injections are the first class of drugs designed from the ground up to prevent migraine. In the large trials, they cut monthly migraine days by roughly half for about half of the patients who tried them, with side effects that are usually mild. They do not work for everyone, and they are expensive, but for people who have been stuck on older preventives that made them feel worse than the migraines, they are often a better option.

If you have four or more migraine days per month and you are still relying mostly on pain pills to get through them, it is worth asking a headache specialist whether a CGRP injection, or one of the older preventives, makes sense for you. The goal is not perfection. The goal is getting enough of your days back that migraine stops running your life.