Could Newer Migraine Drugs Bring You Relief?

If you suffer from migraines, you may find you are living in a constant state of dread as you wait for that recurring, debilitating pain to come back. You may also be fed up with unsolicited advice—“Drink more water!” or “Get more sleep!”—from well-meaning family and friends.

About 12% of Americans suffer from migraines. Globally, women are far more affected than men. In the U.S. alone, nearly three times more women than men have migraines. Researchers are still trying to understand why a significant difference exists between sexes.

What’s more, physicians not trained in headache medicine can sometimes miss or give a wrong diagnosis, says Christopher Gottschalk, MD, a Yale Medicine neurologist and director of Yale Medicine's Headache and Facial Pain Center. And that means the number of migraine sufferers might be much higher than is currently reported.

Researchers have spent decades trying to understand the causes of complex brain disorders like migraine. Without a clear cause, people developed and passed along their own theories—many of them linking triggers and migraines. To be sure, migraine sufferers often avoid triggers that seem to consistently precede their attacks. Certain foods, caffeine, alcohol, an irregular sleep schedule, stress, dehydration, and weather changes are examples of some common triggers.

But studies on the relationship between triggers and migraines have given mixed evidence.

In fact, recent studies haven’t turned up evidence to support the idea that dehydration or lack of sleep, as just two examples, directly lead to migraines, says Dr. Gottschalk. Even stress, which many patients believe causes their migraines, hasn’t emerged as a consistent predictor of attacks, he adds.    

Dr. Gottschalk explains that one stress-related exception is a phenomenon that sounds counterintuitive: a let-down migraine.

“If someone experiences extreme levels of stress at work or school and the stress abruptly stops over the weekend, they may have what’s called a ‘let-down’ migraine,” Dr. Gottschalk says. A small study published in the journal Neurology found that in the first six hours after stress declined, patients had a nearly five-fold increased risk of a migraine. Researchers still don’t know why this happens.

“The point is that migraines should not be treated as a health condition that’s under the individual’s control,” says Dr. Gottschalk. “A migraine is a recurring, episodic neurological disorder—no more under anyone’s control than epilepsy or multiple sclerosis—that needs medications and, sometimes, devices to prevent attacks, lower their severity, and reduce the disability they cause. There is an enormous need to overcome the bias we have all inherited that suggests migraine patients are somehow responsible for their disorder.”

Migraines sufferers endure not just intense pain in their head but also nausea; an inability to tolerate light, noise, or odors; confusion; overwhelming fatigue, and more—to the point that they are unable to keep working or be present with family and friends. This inability to function separates migraines from headaches.

About 25 to 30% of people with migraines experience aura just before an attack comes on. Aura can cause blind spots, flashing lights, or “zig zags” in a patient’s vision and tingling on one side of the body. However patients experience migraines, they usually must retreat to a quiet, low-light space until the throbbing pain—which can last several hours to several days—subsides.

But part of the reason behind misdiagnoses may be that migraine patients don’t describe their symptoms in the way that doctors expect, says Dr. Gottschalk. For example, many patients with migraines have sinus pressure and congestion—even a runny nose or red eyes. “Some doctors, hearing this, might conclude that this is an episode of sinusitis or sinus headache,” says Dr. Gottschalk.

In addition, most patients with migraines report neck pain, tightness, or tenderness with their attacks. “Many doctors have been taught to interpret that as evidence of a ‘cervicogenic’ headache, or pain that originates in the neck but is instead felt in head, which requires muscle relaxants and physical therapy instead of migraine therapy,” says Dr. Gottschalk. “But neck disorders causing headache are rare in comparison to migraines.”

The solution, says Dr. Gottschalk, is for physicians to be trained to treat migraines with the commitment shown to other illnesses, like diabetes, arthritis, or asthma. “We could reduce the amount of time lost to migraine attacks overnight,” Dr. Gottschalk adds.

To start treatment, neurologists usually prescribe patients oral medications for migraine prevention from drug classes originally developed to treat other conditions. Some examples include beta blockers (intended for high blood pressure); tricyclic antidepressants (like amitriptyline and nortriptyline, developed for depression); anti-seizure drugs (created for epilepsy); and injections of Botox (marketed as a treatment to reduce wrinkles in the skin).

To cut short acute attacks, physicians might also suggest a medication from a class of drugs called triptans, the first drug type created exclusively to treat migraine attacks. The first triptan approved by the Food and Drug Administration (FDA) in the early 1990s was Imitrex, also known by the generic name sumatriptan.

While these drugs can successfully prevent or treat migraines for some patients, they also cause side effects—nausea, insomnia, difficulty with memory, drowsiness, hair loss, weight gain, to name a few examples—that interfere with daily life arguably more than the migraines themselves.

“A lot of the time the price is too much to bear for people,” Dr. Gottschalk says. “That’s not a good arrangement.”

In the past couple of years, the FDA approved medications from two new drug classes that target a specific molecule involved in the onset of migraines. What’s more, the drugs cause far fewer side effects in patients.

Aimovig (erenumab) recently became the first drug within a class called monoclonal antibodies to be approved by the FDA to prevent migraines. Thirty years ago, researchers discovered that a molecule called calcitonin gene-related peptide (CGRP) is released by the trigeminal nerve during migraine attacks. The same molecule is also found in other nerves throughout the body, although its function outside the brain is not yet understood.

Aimovig works by blocking the CGRP receptor so that CGRP cannot bind to it. Patients take the drug through self-administered injections, which work similar to an Epi-pen, once a month. Other drugs in this class include Ajovy (fremanezumab) and Emgality (galcanezumab)—also self-administered on a monthly basis—and Vyepti (eptinezumab), which must be given in a hospital or clinic through IV infusion. The injections are given as a preventative.

“We’ve been using these monoclonal antibodies for two years,” Dr. Gottschalk says. “Patients have been very, very happy with them.”

Unlike traditional migraine medications, these monoclonal antibodies have fewer side effects because they are natural proteins and they target a single, specific molecule. Two of the more frequently reported effects include skin irritation at the injection site and constipation. Older drugs tend to have more side effects because they are synthetic chemicals that affect multiple neurotransmitters at the same time and also interfere with functions of other organs, like the liver or kidneys or bone marrow, says Dr. Gottschalk.

The FDA has also approved medications that come in pill form from a class of drugs now called gepants. These target CGRP molecules, too, but are designed to stop acute migraines instead of preventing them. These medications include two drugs so far: Ubrelvy (ubrogepant) and Nurtec (rimegepant).

“Some of my patients have tried these and said they work well without many side effects,” Dr. Gottschalk says. “Having a new treatment option for migraine attacks that is easy to use is a big deal.”

Still, despite advances in the field of migraines and public awareness of them, a stigma around the condition remains.

“People are still ashamed to talk about it,” Dr. Gottschalk says. “But hopefully, as new, effective treatments continue to emerge, that will begin to change."

An earlier version of this story listed incorrect tricyclic drug examples.