Migraine is a common and potentially disabling disorder. Migraine attacks can not only cause severe throbbing head pain or pulsing sensations, but also nausea, vomiting, and extreme sensitivity to light and sound.
There are as-needed treatments to stop symptoms of a migraine attack (acute treatment) and long-term treatments to decrease the frequency and severity of migraine attacks (preventive treatment).
As-needed treatments include nonprescription pain relievers such as aspirin, acetaminophen (Tylenol) or ibuprofen (Advil, Motrin IB, others) or nonprescription pain relievers that include caffeine (Excedrin Migraine). Additionally, triptans, a class of prescription medications designed specifically for migraine — including drugs such as sumatriptan (Imitrex, Tosymra, others), rizatriptan (Maxalt), naratriptan (Amerge), eletriptan (Relpax), or zolmitriptan (Zomig) — can be taken as pills, injections or nasal sprays. However, if taken too frequently, both the nonprescription and prescription acute medications may lead to medication-overuse headaches.
For many years, preventive options for managing migraine were limited to medications originally intended to treat other conditions. These included certain drugs to lower blood pressure, antidepressants and anti-seizure drugs. Although quite effective, these drugs can cause side effects such as nausea and dizziness, which can make it difficult to stick to the treatment.
But the list of available treatments is expanding along with increased knowledge of what is happening in the brain with migraine. Here we have an interview with Amaal Starling, M.D., a Mayo Clinic neurologist, to learn more about advances in treatment.
How are preventive treatments for migraine changing?
Before 2018, there were multiple treatment options for migraine approved by the Food and Drug Administration (FDA), but they were designed initially for other disorders — such as depression — and found to be helpful for migraine in clinical trials. We always thought that if we had something that was designed specifically for migraine, it’s possible that it would work better with fewer side effects.
Migraine researchers found there was a specific protein, CGRP, that was released during a migraine attack, and then when a migraine attack was stopped — say with a medication such as sumatriptan — the blood level of CGRP protein would go down. When they would give study subjects CGRP as an infusion, it would cause a migraine-like attack. So the theory was: Let’s block CGRP and see what happens.
This led to a paradigm shift in the treatment of migraine that started in 2018, when the first CGRP monoclonal antibody for the prevention of migraine was FDA approved. It was the advent of targeted treatment options that are specifically designed for migraine.
There are now four CGRP monoclonal antibodies that have been FDA-approved: eptinezumab (Vyepti), erenumab (Aimovig), fremanezumab (Ajovy) and galcanezumab (Emgality). They’re designed to go find CGRP proteins or CGRP receptors and basically hug them so that they are inactive.
How do these new CGRP medications compare to the older preventive drugs?
Whether we’re talking about our oral preventive medications that we’ve had for decades or these newer CGRP monoclonal antibodies, none of them will work for every person.
Our hypothesis of a migraine-specific drug being better tolerated has proven to be true. With the drugs that were designed for other conditions, there might be more side effects. But with the CGRP monoclonal antibodies in the clinical trials, we found that there were few side effects. One side effect is an injection site reaction, as three of these drugs are given as monthly or quarterly injections. Erenumab also has high blood pressure and constipation as potential side effects.
However, these drugs are not always covered by insurance. Even when they are covered and the copay is reasonable, individuals typically have to try multiple other medications and find them ineffective before they’re allowed to try CGRP drugs. And these are also newer medications, so we don’t know about long-term side effects.
There are also new as-needed migraine medications that target CGRP. How do those compare to older medications?
In the past, triptan medications were the main migraine-specific, as-needed medications that we had — and they worked pretty well. However, based on studies, triptan medications didn’t work for about 30% to 40% of those with migraine. These medications can also potentially narrow the blood vessels, so people with a history of stroke, heart attack, ministrokes or uncontrolled hypertension should not take triptans.
Ubrogepant (Ubrelvy) and rimegepant (Nurtec ODT) are new CGRP receptor antagonists for as-needed treatment of migraine that do not narrow blood vessels. These oral medications block the CGRP receptor to hopefully stop a migraine attack that is already ongoing. More research is needed, but these drugs don’t appear to have the same risk of medication overuse headache that some other as-needed migraine treatments.
Another new as-needed medication that’s not CGRP-related is called lasmiditan (Reyvow). Like triptan medications, it’s a serotonin receptor agonist. However, triptans work on a specific subtype of receptor that narrows blood vessels. Lasmitidan does not work on that subtype of receptor, so it does not have a narrowing effect on the blood vessels. This is great for people who had success using triptans but had to stop using them after having a heart attack or stroke.
Are there any nondrug options for treatment?
A: There are several available noninvasive neuromodulation devices, which deliver electrical or magnetic pulses to your head, neck or arm. These can be great options because they have very few side effects and won’t interact with other medications.
Your brain is like a huge circuit board; electrical currents make us move, talk, think and feel. A migraine results in abnormal electrical activity. Neuromodulation devices work on different parts of the brain and different pathways, but what they’re trying to do is normalize the abnormal electrical activity in the brain.
Devices that are commercially available include single pulse transcranial magnetic stimulation (sTMS mini), external trigeminal nerve stimulation (Cefaly Dual), noninvasive vagus nerve stimulation (GammaCore Sapphire), and remote electrical neuromodulation (Nerivio). These are all FDA approved for the as-needed treatment of migraine, and some are also approved for preventive treatment.
All of these devices are very safe, have few side effects and don’t require surgery. However, they are rarely covered by insurance and can be expensive, so that does limit access to these treatments.
What’s next in migraine treatment?
Even with many options available, some individuals still may not find benefit. They may feel very hopeless. However, while CGRP is our current target, scientists are identifying other targets in the body in individuals with migraine. For example, there is another protein that’s called PACAP that’s under investigation. And we will continue to identify additional molecules and proteins until we find treatment options for every single person with migraine.
In the meantime, I urge everyone to visit the American Migraine Foundation at americanmigrainefoundation.org to learn and advocate for yourself or for your loved ones, to make sure everyone gets the treatment they need for this disabling disease.
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