Your guide to the newest migraine medications

Despite its reputation as just a bad headache, a migraine is actually an intense neurological event that causes more symptoms than head pain. From nausea and vomiting to light sensitivity and fatigue, a migraine can be a completely debilitating illness for those who experience them. 

The Migraine Research Foundation estimates that about 39 million people in the U.S. experience migraine, including men, women, and children. That’s 12% of the population!

Considering that a migraine can start several hours or days before it reaches its peak and cause post-headache symptoms, it’s no wonder that researchers have been developing more drugs aimed at migraine prevention and relief, such as Ubrelvy, Nurtec, and Emgality. 

Why are new migraine medications hitting the market?

Up until the past few years, many migraine drugs available to patients were developed to assist with other health conditions like high blood pressure, depression, and epilepsy. Healthcare providers learned through prescribing some of those drugs to their patients that they also reduced migraine activity—but it was a discovery of chance, not design.

That’s not the case with the new generation of migraine drugs. “With these newer drugs, we have a better understanding of the underlying pathophysiology of migraines, like how and why they yield symptoms, and these meds are a direct reflection of what the researchers have come to understand about how migraine happens,” says Ilan Danan, MD, MSc, a sports neurologist and pain management specialist at the Center for Sports Neurology and Pain Medicine at Cedars-Sinai Kerlan-Jobe Institute in Los Angeles.

The prescription drugs in this new generation of migraine medications fall into two main categories: CGRP antagonists or ditans.

What are CGRP antagonists?

Calcitonin gene-related peptide (CGRP) is a protein released from certain nerve endings around the head and brain; it can cause enlargement of the blood vessels there, triggering inflammation and pain. This inflammatory response is what causes the typical symptoms many migraineurs experience during an attack.

CGRP antagonists, also known as anti-CGRP drugs, can prevent migraine by interfering with the release of this protein. “These drugs work in one of two ways: by binding to CGRP directly and preventing it from binding to pain receptors, or by blocking CGRP at the receptor itself, stopping the mechanism of action that triggers the series of events leading to migraine,” Dr. Danan explains.

Basically, if you can stop CGRP from binding to pain receptors in any way, you can slow down that process and prevent the rollercoaster of migraine symptoms from happening. CGRP antagonists are designed to do exactly that. Anti-CGRP drugs are available in four forms:

• Intravenous infusion
• Orally disintegrating tablets
• Oral tablets
• Subcutaneous injection

These are the newest anti-CGRP drugs and how they compare to previous treatments for migraine.

Vyepti

Receiving FDA approval in February 2020, Vyepti (eptinezumab-jjmr) is the most recent CGRP antagonist approved for the prevention of migraine. It’s the first in this class to be administered by a 30-minute intravenous infusion (IV), given once every three months. It’s only indicated for preventive treatment, but Lundbeck claims it may also offer rapid relief of symptoms within only one day of the IV treatment. This is notable because some people with migraine end up at urgent care or in the emergency room in acute pain. This medication may work as a treatment and preventive measure in those circumstances.

A trial of 888 patients found clinically significant preventive effects in over 50% of participants as early as one day after the infusion. Nearly a quarter of participants had a 75% reduction in migraine days three months after treatment.

Nurtec ODT

Nurtec ODT (rimegepant) is the newest oral CGRP antagonist on the market. It was approved by the FDA on Feb. 27 2020. Nurtec is unique because it’s the only orally disintegrating tablet available. You place it under your tongue rather than swallowing the pill. Meaning, it can provide even quicker relief from migraine pain. 

Additionally, it’s approved for preventive and acute treatment. Your doctor may prescribe Nurtec ODT for you to use on the spot, to get rid of a migraine in progress, or as a drug to be taken every other day to prevent migraine. This is actually fairly game-changing. The American Migraine Foundation has said that, depending on the drug, patients should not take acute medications more than 10 to 15 days a month due to the possibility of medication overuse headaches. 

“With acute medications, the more you take, the more you can turn your episodic migraine into chronic migraine,” explains Mark W. Green MD, emeritus director of Headache and Pain Medicine at Icahn School of Medicine at Mount Sinai. “But what we’ve learned about gepants is that they don’t appear to do this at all, and that’s what lead to Nurtec being studied for prevention as well as acute treatment.” 

Nurtec ODT works to relieve the worst migraine symptoms within two hours of it being administered.

Ubrelvy

When Allergan was granted FDA approval on Dec. 23, 2019, Ubrelvy (ubrogepant) was the first oral CGRP antagonist. It is a pill, swallowed with water. Previously, this type of medication was only available via injection. The benefit is it’s much easier to take. The drawback is that it doesn’t last as long as the injectable forms. Oral CGRP antagonists typically clear your system within a couple of days, according to the American Migraine Foundation.

Unlike Nurtec ODT, Ubrelvy is only approved for the acute migraine treatment. Clinical trials for Ubrelvy have shown it to reduce migraine pain in the majority of participants, with many reporting that nearly all of their debilitating symptoms were gone within two hours after taking it.

Emgality

Emgality (galcanezumab-gnlm) is the most recent anti-CGRP medication approved in an injectable form. It was approved Sept. 27, 2018 for prevention of migraine and treatment of cluster headaches. Produced by Eli Lilly and Company, it is administered once monthly via self-injection using a single dose, autoinjector. It is one of the more widely-used injectables thanks to its relatively low risk of side effects.   

A double-blind study in 2020 published in The Lancet Neurology showed a reduction in migraine headache days for patients using Emgality for three months versus a placebo, and specifically looked at patients who had tried—and failed—to find success with at least two other migraine treatments in the past.

Ajovy

Ajovy (fremanezumab-vfrm) was originally approved, in September 2018, for self-injection using a prefilled syringe. In 2020, it also became available in autoinjector form. A 2019 study published in the Lancet found that four weeks after treatment, some participants experienced 50% reduction in migraine days.

Aimovig

In May 2018, Aimovig (erenumab-aooe) became the first CGRP antagonist approved to prevent migraine. It’s administered once monthly via self-injection. Some studies have found that Aimovig has more side effects than more recently approved injections. For example, Aimovig has been shown to result in higher incidences of elevated blood pressure. Yet, as the oldest of this class of medication, Amgen maintains that it has the best safety and efficacy profile.

What are ditans?

For many migraineurs, triptans are a tried-and-true favorite when it comes to acute medications, but they do have drawbacks: They need to be taken early in a migraine attack to be effective, they are usually not prescribed to people with a history of heart disease, and they can interact with a variety of other medications, including antidepressants and MAOI inhibitors. 

Ditans are slightly similar to triptans, but interact with different receptors. They don’t restrict blood vessels like triptans do, which makes ditans safer for people with a history of heart problems. Instead, they work along specific serotonin receptors in the brain that transmit pain signals.

However, there are some issues with ditans, like Reyvow. “It’s a controlled substance,” Dr. Green says, “so it comes with addiction warnings, and you can’t drive within eight hours of taking it.”

For patients with a history of heart problems, ditans can be a safe way to treat migraine, but they aren’t generally recommended for the majority of patients because of these additional risks.

Reyvow

Reyvow (lasmiditan) is the first and only ditan to be FDA approved for the treatment of migraine. It was approved in October 2019 as an oral tablet. According to manufacturer Eli Lilly and Company, the exact way Reyvow works is not fully understood; neither is why the specific pain receptors it interacts with are so important in developing a migraine, but the clinical trials for Reyvow have shown promising results since its release.

According to one phase three study published in 2018 in Neurology, Reyvow was significantly more effective in reducing patients’ migraine symptoms within two hours when compared to a placebo, and with only mild to moderate side effects. The participants studied all had a “high level of cardiovascular risk factors,” per the study’s authors.

Compare migraine medications

It can be confusing to consider all your options for treating and preventing migraine, especially with the new generation of drugs being released to target migraine. Here is a comparison of common drugs currently FDA-approved for the treatment of migraine so you can get a closer look.

Ask your doctor about new migraine meds

If you’re currently happy with your migraine treatment, then don’t rock the boat! There’s no need to make changes if what you’re doing or taking is working. But if you’re one of the more than 50% of migraine sufferers who is unsatisfied with their treatment, it’s more important than ever to reach out to your doctor.

Why? Because there used to be a limited number of medications you could try when looking for pain relief; if you struck out with those, you didn’t have many other options. Now, however, there are several new drugs available to migraineurs—and more are being released all the time. For example, Trudhesa (dihydroergotamine)—a new formulation of the older, injectable migraine medication Migranal—was approved as a nasal spray in September 2021 for acute treatment of migraine. There are also newer, more effective formulations of sumatriptans for severe migraines. 

While you may not be a candidate for every single one (and, in some cases, you may run into trouble receiving insurance coverage for some of the newer-generation drugs), many of them are considered largely safe and effective for the average migraine sufferer.

Dr. Green says the FDA is requiring that drug manufacturers conduct phase IV studies, or post-marketing surveillance, on these new generation drugs, and that results among huge numbers of people show that they are performing well and safely.