For the first time in 14 years, doctors have updated guidelines for preventing migraine attacks.
The new recommendations from the American Academy of Neurology and American Headache Society, published August 31 in Neurology, incorporate evidence on treatments that weren’t available when the guidelines were last updated. That includes drugs that target calcitonin gene-related peptide, or CGRP. These drugs, like Aimovig and Ajovy, have been a game changer for some, reducing migraines in up to 70 percent of the people who take them.
Some come in tablet form, while others are injected under the skin or infused into a vein. Because the previous guidelines were written before these drugs were developed, they had recommended beta-blockers, like Propranolol and Metoprolol, as well as certain antiseizure medications for migraine prevention. These drugs also appear in the updated guidelines as options for patients who want a medication with a longer track record or a lower cost than CGRP-targeted drugs.
The latest guidelines recommend offering preventive treatment to people with frequent migraine attacks or whose migraine significantly interferes with work or daily activities; that’s roughly 8 million adults in the United States. The previous guidelines did not include explicit criteria for patients eligible for preventive treatment.
“My hope is that this guideline helps clinicians feel more comfortable prescribing preventive treatments for people with migraine,” Rebecca Burch, a headache medicine specialist at the University of Vermont Medical Center in Burlington, said during an Aug. 26 news briefing.
Science News spoke with Amaal Starling, a neurologist specializing in headache at the Mayo Clinic in Phoenix, about the advances reshaping migraine prevention and the challenges that remain. Starling was not involved in creating the guideline updates. This conversation has been edited for clarity and length.
SN: What’s the biggest change in migraine treatment since the last guidelines came out in 2012?
Starling: The biggest scientific shift in how we treat migraine now compared to five to 10 years ago is specifically with migraine prevention. The goal of migraine prevention is to reduce the frequency and severity of migraine attacks.
For the first time, we have disease-specific, mechanism-based, targeted treatment options for migraine prevention, and these are the CGRP-targeted treatment options. CGRP is a protein that is involved in migraine. Levels of CGRP rise during a migraine attack and fall when a migraine attack has been well-treated or resolved. Because these medications are disease-specific, mechanism-based and targeted, they have high rates of efficacy and high rates of tolerability meaning very minimal side effects. Patients are able to stay on these medications for longer periods of time.
All these factors have led to a paradigm shift in prioritizing these medications when medically appropriate. In fact, the American Headache Society has a position statement that indicates that CGRP-targeted treatment options for the prevention of migraine should be considered as first-line treatment options for patients living with migraine.
SN: What guides how you decide on a preventive treatment?
Starling: Currently, we will look at patient preference on the delivery of the medication and their comorbidities. When patients ask me what medication is best for them, I will often say, “the one that you will take.” If the patient has difficulty taking a daily pill or they have a fear of needles, I will try to identify a treatment option that will suit the patient’s preferences to increase adherence and persistence of a treatment regimen.
In addition, many patients with migraine have comorbidities, like anxiety, depression, insomnia, obesity, hypertension or other conditions. There are medications that could be beneficial not only for migraine prevention but also for one of those comorbidities. There are multiple factors in evidence-based guidelines, individual medical history and patient preferences that we take into consideration when identifying the optimal treatment regimen for an individual patient.
SN: If newer drugs target migraine biology more precisely, why can’t doctors yet predict which treatment will work best for a particular patient?
Starling: Migraine is a genetic neurologic disease. However, the most common type of migraine is not based off a single mutation but rather multiple genetic variants that have led to vulnerability of developing migraine disease and migraine attacks. To date, there have been over 100 different genes and over 200 different genetic variants or mutations that have been identified as potentially leading to vulnerability to migraine.
Migraine is not a one-size-fits-all disease, and it cannot be treated with a one-size-fits-all treatment because of this genetic and clinical heterogeneity. We hope that soon we will be able to practice individualized, personalized medicine, where based on biomarkers like lab work or imaging or clinical characteristics, we can predict whose migraine disease may benefit from one medication versus another.
SN: What are researchers learning from people who don’t respond to CGRP-targeting drugs?
Starling: We know that CGRP is one of the mediators of migraine, however, we also know that there are multiple other mediators and mechanisms that may be involved and may vary from one person to another.
If there is an individual or patient who does not respond to CGRP targeted therapies, it tells me that they may not have as much of CGRP-related pathophysiology in their underlying migraine disease. This is why we continue to investigate other novel mediators of migraine including another pain signaling neuropathic tied called pituitary adenylate cyclase-activating polypeptide, or PACAP, which is currently undergoing clinical trials. In addition, there are many other novel targets that are currently under investigation for the treatment of migraine.
SN: Are there any developments coming down the pike that excite you?
Starling: What excites me most isn’t one single drug that is in the pipeline, but rather the fact that the paradigm has shifted from nonspecific preventive therapies to disease-specific, mechanism-based, targeted preventive treatment options, that have improved efficacy, better tolerability, decreased disability and improved patient-reported outcomes.
