Migraine is an all-too-common and potentially disabling disorder. Migraine attacks can cause severe throbbing head pain or pulsing sensations, as well as nausea, vomiting, and sensitivity to light and sound.
Some treatments stop symptoms of a migraine attack (acute, or as-needed treatment) and other long-term treatments decrease the frequency and severity of migraine attacks (preventive treatment).
As-needed treatments include:
- Nonprescription pain relievers. These include aspirin, acetaminophen (Tylenol, others) or ibuprofen (Advil, Motrin IB, others)
- Pain relievers that include caffeine. Excedrin Migraine is a popular example.
- Triptans. This is a class of prescription medication designed specifically for migraine — including drugs such as sumatriptan (Imitrex, Tosymra, others), rizatriptan (Maxalt), naratriptan (Amerge), eletriptan (Relpax) or zolmitriptan (Zomig). These can be taken as pills, injections or nasal sprays.
If taken too frequently, both the nonprescription and prescription acute medications may actually lead to worsening headaches, known as medication-overuse headache.
For many years, preventive options for migraine were limited to medications that had originally been intended to treat another condition, such as drugs to lower blood pressure, antidepressants and anti-seizure drugs. But these drugs can cause side effects such as nausea and dizziness that can make sticking to treatment difficult.
With increased knowledge of what is happening in the brain with migraine, the list of available treatments is expanding. Read on for an interview with Amaal Starling, M.D., a Mayo Clinic neurologist, to learn more about advances in treatment.
Q: How are preventive treatments for migraine changing?
A: Multiple FDA-approved treatment options for migraine have existed for a long time, but they had all first been designed for other diseases — such as depression — and were found to be helpful for migraine in clinical trials. We always thought if we had something that was designed specifically for migraine, it’s possible that it would work better with fewer side effects.
People studying migraine found a specific protein, CGRP (calcitonin gene related peptide), that was released during a migraine attack. When a migraine attack was stopped — say with a medication like sumatriptan — the blood level of CGRP protein would go down. When they would give study participants CGRP as an infusion, it would cause a migraine-like attack. And so, the theory was: Let’s try to block CGRP and see what would happen.
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 preventive treatment options that are specifically designed for migraine.
Now we have four CGRP monoclonal antibodies that have been FDA-approved:
- Eptinezumab (Vyepti)
- Erenumab (Aimovig)
- Fremanezumab (Ajovy)
- Galcanezumab (Emgality)
They’re designed to find CGRP proteins or CGRP receptors and basically hug them so that they are inactive.
We also have two CGRP receptor antagonists that reduce CGRP receptor activity:
- Rimegepant (Nurtec ODT)
- Atogepant (Qulipta)
Q: How do these new CGRP medications compare to the older preventive drugs?
A: Whether we’re talking about our oral preventive medications that we’ve had for decades or these newer medications that reduce CGRP activity, none of them will work for every person.
Our hypothesis of a migraine-specific drug being better tolerated has turned out to be true. With the drugs that were designed for other conditions, there might be more side effects. But with the CGRP-related medications in clinical trials, we found few side effects. For the monoclonal antibodies, 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 well covered by insurance. Even when they are covered and the copay is reasonable, individuals would typically have to try multiple other medications and find them ineffective before they’re allowed to try the anti-CGRP drugs. And these are also newer medications, so we don’t know what the long-term side effects are.
Q: There are also new as-needed migraine medications that target CGRP. How do those compare to older medications?
A: 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 blood vessels, so people with a history of stroke, heart attack, mini-strokes or uncontrolled hypertension should not take triptans.
Two new CGRP receptor antagonists are available for as-needed treatment of migraine — and they don’t narrow blood vessels. These are ubrogepant (Ubrelvy) and rimegepant — rimegepant is also approved for preventive treatment of migraine. These are oral medications that block the CGRP receptor to hopefully stop a migraine attack while it’s happening. 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 do.
Another new as-needed medication that’s not CGRP-related is called lasmiditan (Reyvow). Like triptan medications, it works on serotonin receptors, but works on a different subtype of these receptors so does not narrow blood vessels. This is great for people who had success using triptans but had to stop using them after a heart attack or stroke.
Q: What’s next in migraine treatment?
A: Even with the plethora of options available, some individuals still need more options. They may feel very hopeless. However, scientists are working to identify other targets in migraine. For example, there is another protein that’s called PACAP (pituitary adenylate cyclase activating peptide) 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, visit the American Migraine Foundation to learn and advocate for yourself or for your loved ones, to make sure everyone gets the treatment they need for this disabling disease.
