In Barrow Study, International Headache Experts Define Most Severe Migraine

Goal Is to Improve Care for Millions of Migraine Sufferers

(PHOENIX – Jan. 6, 2025) – A panel of international headache experts has formally defined the most severe form of migraine with the goal of improving care for millions of headache sufferers.

It’s called refractory migraine—and it can occur daily, disrupting patients’ lives and sometimes creating a sense of hopelessness among those who suffer from them.

“Refractory migraine does not respond to any currently available treatments, and this study provides a formal definition to help identify these patients clinically and for research,” said the study’s lead author, Jennifer Robblee, MD, associate professor of neurology at Barrow Neurological Institute, which is part of Dignity Health St. Joseph’s Hospital and Medical Center. “It builds off a previous proposed definition, but this is the first time that an international consensus has been reached.”

The study was first published in September 2025 in Cephalalgia, the journal of the International Headache Society.

The study is a Delphi consensus carried out by a group of international experts in headache medicine. The Delphi consensus led to the development of four key categories: refractory migraine, probable refractory migraine, resistant migraine, and treatment-responsive migraine.

“These four categories may aid in enrollment for studies on pathophysiology, biomarkers, and new treatment targets,” the study said. “Clinically, the criteria for refractory and resistant migraine will help with clinical decision-making by reinforcing the need to try evidence-based treatments and by providing guidance regarding when to try more aggressive treatment approaches. These criteria may also increase attention to this population’s disease burden to help advocate for them as a specific migraine subgroup.”

The study is important because migraine is often overlooked or not diagnosed. Migraine impacts 37 million men, women, and children in the U.S., according to the American Migraine Foundation, but only 5% have been seen by a health care provider, received an accurate diagnosis and obtained appropriate care.

“Having a formal definition for refractory migraine will help clinicians identify these patients as it impacts goals of care and discussion of off-label treatments trials beyond our guidelines,” Dr. Robblee said. “In research, it helps ensure we are consistent in who enrolls in studies about refractory migraine.”

Researchers said the four key diagnostic categories are crucial for accurately categorizing patients’ disease based on burden and treatment response, as well as for advancing research on pathophysiology, biomarkers, and future treatment targets for refractory migraine.

Clinically, they provide a structured framework for decision-making, reinforce the importance of evidence-based treatments, and help guide the use of more aggressive treatment strategies when necessary.

“The validation of these criteria in diverse clinical settings is still needed,” the study said.