Lars Edvinsson has been involved in the development of the migraine medicine that uses CGRP inhibitors, from its beginning in the 1980s to today.

Patients are being forced to take regular breaks from effective migraine medicine. But how do these expensive injections really work?

Forty years ago, researchers discovered a protein that dilated blood vessels in the brain. It led to a whole new type of migraine medicine.

For many patients with chronic migraines, this new medicine has given them their life back. Now patients are afraid of being forced to endure hellish pain, according to the Norwegian Broadcasting Corporation (NRK) and the national newspaper Dagsavisen.

Every three years, these patients are required to take a three-month break from their medicine. This is what the Norwegian Directorate of Health and the Norwegian Medicines Agency have said in their new guidelines.

After an uproar in the media, however, the guidelines were quickly changed. Doctors are now allowed to use their discretion and halt the break earlier if necessary.

But what’s so special about these expensive medicines? And should even more people who have migraines be allowed to use them?

A 40-year-old discovery

To understand how CGRP inhibitors differ from other migraine medications, we have to go back to the 1980s.

It was then that the Swedish researcher Lars Edvinsson and his colleagues discovered that a special protein played a role in the disabling pain disorder.

The substance was called calcitonin gene-related peptide, which is abbreviated CGRP.

This protein was the only substance released in the body of people with migraines during an attack.

A mistaken belief

The most obvious effect of CGRP is that it dilates blood vessels in the brain.

That led several researchers to believe that blood vessels could be the explanation for the pain that people with migraines experienced.

This was a mistake, Edvinsson said to

The protein turned out to have a different, more important role in the brain.

“Migraines have gone from being a lesser priority condition to having gained prestige with a lot of research on them in Norway and around the world,” says Lise Øie.

Pain signal

There are a number of different nerves inside our head. Some of them send signals when the face is touched.

In people with migraines, these nerves become overactivated. This is caused by CGRP.

“CGRP is a kind of pain signal,” says Edvinsson.

Some of the nerves in people with migraines release large amounts of the protein during the migraine attack. The substance attaches to its own receptors found on other nerves. It becomes a signal that the brain interprets as intense pain.

During an attack, people who are affected tend to be hypersensitive to light and sound. And they can be in such pain that they become nauseated and vomit.

Hallelujah feeling

The discovery of this pain signal opened the door to a new way of treating migraines.

The idea is simple: stop the protein.

But it would take almost 40 years before CGRP inhibitors came on the market.

The drug came to Norway in 2019. At that time, it was also decided that patients with chronic migraines should be given the new medication and that the state would pay.

“There was a bit of a hallelujah feeling in the headache community when these drugs arrived,” Lise Øie said to She is chief physician at the Department of Neurology and Clinical Neurophysiology at St. Olavs Hospital.

“Finally, there was a medicine that was developed specifically for migraines,” Øie said. She is also studying preventive treatments for migraines at the Norwegian National Advisory Unit on Headaches.


There are several preventative medications that work against migraines, including antidepressants, Botox and antihypertensives. But they are really meant for other conditions.

CGRP inhibitors are an injection that contain antibodies. Inside the body, these bind to either CGRP or to the receptors for CGRP.

The antibodies simply block the pain signals.

The new medicines don’t work for everyone

But the injections are expensive. They cost thousands of Norwegian kroner a month per patient.

So how effective are these medications really?

According to Edvinsson, one in four who receives the treatment is almost completely healthy. Two out of four have a moderate effect, while the fourth gets no help from the medicine.

Why it works on some and not others, researchers do not yet know.

Edvinsson still believes the new medicines have a fantastic effect.

Not against taking a break asked the Swedish researcher what he thinks about the new Norwegian guidelines that require patients to take a break in treatment every three years.

“I'm not so against it,” Edvinsson said.

Migraines can go away. For that reason, he thinks it’s important that doctors check regularly whether the patient still needs the medication.

“But it’s important not to be too strict in requiring the break to last for three months,” he adds.

Should get to test all three medications

Anne Hege Aamodt is chief physician and head of the headache clinic at the Oslo University Hospital Rikshospitalet. She has been critical of the new guidelines, which she has explained to Dagens Medisin, among other media. Dagens Medisin is an online news site targeted to Norwegian health personnel.

The fact that doctors are now allowed to use their discretion makes the requirement for a break in the use of the medication easier to swallow. But she wants more changes.

She believes that people with chronic migraines should be allowed to try all three medicines available on the market, if the first two do not work.

The limit is currently set at two.

“A significant proportion of migraine patients see an effect from the third medication even if they do not have a beneficial effect from the first two. The government restriction leads to differential treatment between people who can afford to pay for themselves and those who cannot,” Aamodt says.

Anne Hege Aamodt is also critical of the requirement that requires people who use CGRP inhibitors to have 30 per cent fewer days with migraines a month to be able to continue taking the medicine. “We have many patients who have such a good effect that it makes the difference whether they can stay at work or not, but who have no clear reduction in the number of days,” she said.

More could benefit from the expensive medicines

And perhaps even more patients could benefit from these medications.

During the clinical studies of CGRP inhibitors, another treatment group also saw improvements.

These were individuals on the borderline for meeting the criteria for having chronic migraines. They usually have 8−14 days of headaches a month.

This restriction is only motivated by money, Edvinsson said.

“The day the cost drops significantly, the authorities will release it for use for more people,” he says.

Two different budgets

Aamodt believes it would have paid off financially for society to give these patients who are in the grey zone the expensive medicine now.

She points to the enormous expenses that NAV, the Norwegian Labour and Welfare Administration, pays for everyone who is reported sick or disabled by migraines.

“The challenge is that one cost is a health expense on one budget, while sick leave is on another budget,” Aamodt said.

Lise Øie from St. Olavs Hospital points out that a number of people who are severely affected by migraines, but who don’t meet the strict definition of having chronic migraines, will also have a better quality of life if they were covered for these medications.

“Going from being bedridden due to migraines to being able to be with the children at activities or be social with friends, is like getting your life back,” she said.

Translated by Nancy Bazilchuk


Lars Edvinsson et al.: CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nature reviews neurology, 2018. (Summary)


Read the Norwegian version of this article at

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