Brain Research Fuels New Migraine Treatments

Medically Reviewed by Neil Lava, MD on May 01, 2017
From the WebMD Archives

April 27, 2017 -- Migraines are intense, painful, and incredibly common, affecting nearly 960 million people worldwide.

Although several medications can treat migraines, they don’t work for everyone, and some could affect the heart.

To come up with other potential treatments, researchers are using new insights about the brain to target migraines in new ways. They talked about some of these drugs and other treatments in development at the recent 2017 American Academy of Neurology Annual Meeting.

These severe headaches are the seventh leading cause of disability globally. Many people who get migraines have trouble finding relief.

"An individual patient only has about a 45% chance of responding to any one therapy. And we're really bad at determining which individual is likely to respond to which specific therapy," Mayo Clinic neurologist Todd Schwedt, MD, said at the conference.

Migraines are complicated, and that's one of the reasons it's so hard to find a good treatment. "Migraine is not simply a headache, but a complex array of symptoms that can begin hours before the headache begins, and outlast the headache by hours," said Andrew Charles, MD, a professor of neurology at the UCLA David Geffen School of Medicine.

Brain Imaging Sheds Light on Migraine Causes

Doctors used to think of migraines as only a disease caused by widened blood vessels in the brain. Many of the drugs that now treat migraines -- like ergots and triptans -- work based on this principle, by narrowing blood vessels. But constricting the blood vessels can have some serious effects on the heart, making these drugs an unsafe choice for anyone with heart disease.

Schwedt says researchers now view migraine as a brain disease. "I think we've come a long way in the field of headache and migraine in the last few decades."

Tests like positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have allowed scientists to see firsthand the changes that take place in the brain during a migraine. These tests have offered a window into how the brain works during the different phases of these headaches.

For example, in the prodromal phase -- symptoms like irritability, fatigue, and food cravings that appear a day or two before the headache -- different areas of the brain "light up" on scans based on which symptoms a person has. People with light sensitivity, for example, have more activity in the area of their brain that deals with visual information. People with migraines have more activity overall in the regions in their brain that deal with pain.

Imaging scans have also highlighted the role of amino acids in triggering migraine attacks. Scientists have discovered that the levels of two amino acids -- calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) -- rise during migraines. This discovery has led to a new generation of more targeted migraine drugs that cut how often you have headaches without having risky effects on the heart.

New Migraine Drugs in the Pipeline

Researchers at the meeting discussed a few drugs under investigation that aim to stop migraines by blocking the action of CGRP. These include monoclonal antibodies like eptinezumab, erenumab, fremanezumab, and galcanezumab, which are given through a vein (IV) or as a shot under the skin. Another class of drugs, called CGRP antagonists, which include atogepant and ubrogepant, are taken by mouth.

A trial presented at the meeting is testing how safely and well erenumab treats episodic migraines (14 or fewer headaches a month). In the study, a once-a-month dose of the drug lowered the number of headache days and the need for migraine medicines.

Other monoclonal antibodies that have been tested in studies also seem to cut the number of migraine days. The most common side effects reported with some of these drugs included colds and other upper respiratory tract infections.

All of the drugs are still in clinical trials and are not yet available.

PACAP is another substance researchers are studying as a possible migraine treatment target. PACAP is in sensory nerves in the brain, and it may be involved in the pain signaling process.

A Stimulating New Way to Treat Migraines

Drugs aren't the only new therapy that stops migraine pain. Another new avenue of treatment, called neuromodulation, sends an electrical impulse to nerves that are involved in migraines. This technology can prevent and treat migraines without causing harmful side effects.

Single-pulse transcranial magnetic stimulation (sTMS) is a portable device users hold against their head. It sends a pulse through the skin to halt migraine attacks. The Spring TMS device is FDA-approved to treat migraine with aura, with a doctor's prescription. It costs $750 for a 3-month rental, which often isn't covered by insurance. Side effects include ringing in the ears, dizziness, worsening of migraines, and tingling in the back of the head after using the device.

Transcutaneous supraorbital neurostimulation (t-SNS) treats episodic migraines with or without aura. It's placed on the forehead with a headband. A low-level electrical current stimulates the trigeminal nerve, which is partly responsible for the pain of a migraine. The Cefaly t-SNS device costs $349, plus around $30 for a set of electrodes to use with it. Some people who used the device say they had a skin reaction, or a prickling feeling on the skin.

Another new device uses an electrical current to stimulate the vagus nerve in the neck. The transcutaneous noninvasive vagus nerve stimulator (gammaCore) can prevent and relieve migraine attacks. A 2016 study found that vagus nerve stimulation lowered the number of headache days without causing any major side effects. The FDA recently approved gammaCore to treat cluster headaches, but not migraines. This device isn't yet available in the U.S.

Show Sources

2017 American Academy of Neurology Annual Meeting.

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National Headache Foundation: "Facts About Triptans."

Neurology: "Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study."

Pain and Therapy: "Transcutaneous supraorbital nerve stimulation (t-SNS) with the Cefaly device for migraine prevention: A review of the available data."

The Journal of Headache and Pain: "Single-pulse transcranial magnetic stimulation (sTMS) for the treatment of migraine: evaluation of outcome data for the UK post market pilot program."

The Lancet: "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015."

The Migraine Trust: "Transcutaneous vagus nerve stimulation."

Current Opinion in Neurology: “Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies."

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