Migraine Isn’t Just Headache — This Drug Might Treat It All
A new study finds that taking Ubrelvy (ubrogepant) at the first sign of early symptoms like fatigue and brain fog may reduce the severity of a migraine attack.
A well-established pill for migraine may also relieve debilitating non-headache symptoms that occur just as an attack is beginning, including fatigue, brain fog, and light and sound sensitivity.
Results from late-stage clinical trials, recently published in the journal Nature Medicine and funded by drugmaker Abbvie, show that ubrogepant (Ubrelvy) can ease these early migraine symptoms that come on hours or even days before headache.
The U.S. Food and Drug Administration approved Ubrelvy tablets in 2019 for the immediate treatment of migraine with or without aura (flashing lights, zigzag lines, a temporary loss of vision, or other disturbances) in adults. The drug is safe and has few side effects.
“Our data reinforce taking the medicine before headache starts,” says lead study author Peter Goadsby, MD, PhD, director of the National Institute for Health and Care Research Clinical Research Facility and professor of neurology at King’s College in London.
“The results reinforce that we are taking the non-headache symptoms seriously, that we understand them better, and now can treat what are very disabling manifestations of migraine,” Dr. Goadsby says.
Pre-Headache Symptoms of a Migraine Episode Are Common
An estimated 39 million Americans live with migraine, a neurological disease that causes headache with severe throbbing pain or a pulsing sensation, usually on one side of the head. These attacks often include nausea, vomiting, and extreme sensitivity to light and sound.
Just over three-quarters of people with migraine experience prodromal symptoms up to 24 to 48 hours before headache starts.
Ubrelvy Led to a Significant Reduction in Pre-Headache Symptoms
This trial involved over 400 participants aged 18 to 75 who had at least a one-year history of migraine and were able to identify prodromal signs of a pending attack. About 9 out of 10 were white women.
They were randomly assigned to take either a 100-milligram dose of ubrogepant or placebo when they first had early symptoms and felt confident that a headache would start within one to six hours.
During the course of the 60-day trial, participants who took ubrogepant reported reductions in the severity of all of their prodromal symptoms in the 24-hour period following treatment compared with placebo.
The results highlighted that when people took the drug at first sign of early symptoms, they were more likely to have:
Better concentration and less dizziness after one hour
An absence of light sensitivity after two hours
A reduction of fatigue and neck pain after three hours
Four hours after taking the medication, participants were less likely to still be feeling sensitive to sound.
Based on these positive outcomes, Goadsby says it would benefit people with migraine to learn more about early symptoms so they can better manage them.
“Education is key,” he says. “It is remarkable how many patients do not make the association between [early] symptoms and the migraine.”
Recognizing Potential Study Limitations
While the results were statistically significant, the so-called effect sizes of the medication compared with placebo were not that large in many cases, according to Gregory Dussor, PhD, head of the neuroscience department at the University of Texas at Dallas.
For example, the absence of light sensitivity at hour 2 after treatment was reported in about 20 percent of those taking the drug versus roughly 13 percent of those taking placebo.
“The problem with migraine drug studies is there is almost always a very large placebo response — as there are in pain drug trials as well — so it makes it challenging for the active drug to beat the placebo,” Dr. Dussor says.
Taking the drug when noticing early symptoms may already be too late to block an attack completely, and this may explain in part why the effect size was small, according to Dussor, who was not involved in the study.
He adds that devices like smartwatches or other wearable sensors may have the potential to alert someone that they are entering a migraine attack well before they would ever notice on their own.
“If a smartwatch alerted the person to take the drug six hours before any prodrome symptoms started, how much better would it have worked?” says Dussor. “We need more studies aimed at trying to train smart devices to recognize symptoms earlier than any person is capable of recognizing them.”
Another factor to consider is ubrogepant is a type of drug called a CGRP inhibitor (calcitonin gene-related peptide receptor antagonist). Dussor says that some people have the CGRP protein as a major contributing element to their attacks, and so they respond very robustly to drugs targeting CGRP — but other people with migraine don’t respond much at all.
“If you have too many people who are CGRP nonresponders, the effects in the actual responder population won’t look as large because there are so many other people who simply don’t respond to these drugs,” he says. “The challenge is to figure out how to identify the responders.”
He suggests that if this trial was done again, effect sizes may be larger if the only subjects recruited were those who have shown a response to CGRP drugs in the past. For Dussor, the study results demonstrate that CGRP is contributing not just to the headache phase, but to the prodromal phase as well.
“Migraine is more than a headache — it is a brain disease that has multiple manifestations,” says Goadsby. “Be on the lookout for them, listen to your body warning you, and heed the message.”
EDITORIAL SOURCES
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Resources
Goadsby PJ et al. Ubrogepant for the Treatment of Migraine Prodromal Symptoms: An Exploratory Analysis from the Randomized Phase 3 PRODROME Trial. Nature Medicine. May 12, 2025.
Tom Gavin joined Everyday Health as copy chief in 2022 after a lengthy stint as a freelance copy editor. He has a bachelor's degree in psychology from College of the Holy Cross.
Prior to working for Everyday Health, he wrote, edited, copyedited, and fact-checked for books, magazines, and digital content covering a range of topics, including women's health, lifestyle, recipes, restaurant reviews, travel, and more. His clients have included Frommer's, Time-Life, and Google, among others.
He lives in Brooklyn, New York, where he likes to spend his time making music, fixing too-old electronics, and having fun with his family and the dog who has taken up residence in their home.
Don Rauf has been a freelance health writer for over 12 years and his writing has been featured in HealthDay, CBS News, WebMD, U.S. News & World Report, Mental Floss, United Press International (UPI), Health, and MedicineNet. He was previously a reporter for DailyRx.com where he covered stories related to cardiology, diabetes, lung cancer, prostate cancer, erectile dysfunction, menopause, and allergies. He has interviewed doctors and pharmaceutical representatives in the U.S. and abroad.
He is a prolific writer and has written more than 50 books, including Lost America: Vanished Civilizations, Abandoned Towns, and Roadside Attractions. Rauf lives in Seattle, Washington.
