New guidelines released Monday highlight the many new treatments that have hit the market in recent years for the prevention of migraine.
The guidance for health care providers comes from the American Headache Society and the American Academy of Neurology, which last updated their recommendations in 2012.
“There has been a wealth of new treatment available,” said Rebecca Burch, guideline co-author and neurologist at the University of Vermont Medical Center. Burch also co-authored the previous guidance.
Among the key updates are at least a half dozen medications that were approved for migraine prevention by the Food and Drug Administration since 2012. Many of those focus on blocking the calcitonin-gene related peptide, or CGRP, pathway, which is implicated in migraine.
The new guidelines advise doctors to offer preventive treatment to people who have at least four migraine or severe headache days per month, or whose migraines interfere with their ability to work or complete daily tasks. An estimated 15% of Americans experience migraines, with women disproportionately affected. Many try to manage their pain with over-the-counter options once an attack has begun.
Preventive options can reduce the frequency of headache days, but many patients don’t know they qualify for those treatments.
“We know from studies of the U.S. population that many more patients with migraine are eligible,” Burch said in a news conference.
The guidelines include recommendations for less frequent, episodic migraines as well as chronic migraine, which is defined as headache on 15 or more days per month for over three months. At least eight of those headache days must include the features of a migraine, such as severe pain that lasts for hours or days. Migraine can also include nausea, aura, light sensitivity, or discomfort with loud sounds.
Newer therapies, such as the CGRP-targeting medications atogepant (Qulipta), eptinezumab (Vyepti), erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality), received high marks for their efficacy and tolerability. They were also recommended as a preventive option for patients who frequently rely on pain medication once their attacks begin. Some people experience a reduction in headache frequency once they taper down their acute pain medications.
The guidelines also highlight older treatments, including Botox for chronic migraine, propranolol for episodic migraines, and the anti-seizure drug topiramate, that have more long-term safety data. Botox is well tolerated among migraine patients, according to studies the authors reviewed.
Clinicians should check how well treatments are working after eight to 12 weeks, per the recommendations.
“Guidelines are one way that groups like the AAN and the AHS can help improve patient outcomes,” Joanna Kempner, a sociology professor at Rutgers University, said. Kempner, who was not involved in the recommendations, studies the politics of pain and has written two books about headache disorders. “A strong recommendation provides physicians with much-needed ammunition in their fights for prior authorization.”
However, better outcomes depend on patients’ ability to seek and afford health care, she said.
That was top of mind for Andrew Charles, director of the UCLA Goldberg Migraine Program, as he read the new guidelines. (Charles was not involved in their creation, but is the immediate past president of the headache society, and knows several of the authors professionally.)
The recommendations are sorted based on qualifications, like whether evidence of efficacy is a top concern versus tolerability or long-term safety. There are also separate recommendations for different categories of patients — those with a high body mass index, fibromyalgia, or hypertension, or who might be pregnant. “Frankly, I think it’s going to scare away primary care doctors from using it because of how complicated it is,” Charles said.
In some places, the guidelines may cause confusion. For example, the scientific review found the tricyclic antidepressant amitriptyline to be a viable migraine treatment option for some pregnant patients. However, the American College of Obstetricians and Gynecologists advises against using tricyclic antidepressants during pregnancy due to the risk of major congenital abnormalities and other serious problems.
In another instance, the guidelines recommend topiramate as an effective preventive migraine medication. It is also recommended as a good option for patients with a high BMI, since some studies show it can aid with weight loss. But topiramate is also known to cause birth defects, and can make hormonal birth control less effective when taken at higher doses. Clinicians would need to reconcile those contradictions to figure out the best treatment for their patients.
Kempner and Charles both pointed out that candesartan, a generic hypertension medication often used to treat migraine in the U.S. and Europe, was dinged in the guidelines for having “insufficient evidence to support its use.” However, the drug is well tolerated, more affordable than other treatments, and has shown in several placebo-controlled studies to be effective at migraine prevention, Charles said.
Also downplayed was rimegepant, a CGRP-blocking medication sold under the brand name Nurtec, which was approved by the FDA in 2021 as a preventive treatment for episodic migraine. The guidelines recommend rimegepant for patients with episodic migraine only if they don’t respond to medications “with higher evidence.”
“Payers will often find any reason they can to not approve access to a specific medication,” said Charles, who has worked as a consultant for several companies that make migraine treatments listed in the guidance. “If you create these multiple layers of qualifications, then that provides an opportunity for the payers to decline coverage.”
The American Academy of Neurology did not return STAT’s request for comment.
The process to update these guidelines began in January 2018, so various migraine treatments entered the field as the group reviewed the latest scientific evidence. Burch said the process took so long because there was a lot of literature to review.
The group tasked with writing new recommendations included 19 headache specialists and researchers from around the U.S., plus several experts from Canada. About one-third of the panel had relevant conflicts of interest, so were not allowed to rate or review evidence, but voted along with the rest of the group on the recommendations. Conflict-free authors led the development of the guidelines.
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