A migraine drug commonly used to treat headache pain may also alleviate the early, non-pain symptoms that often precede a migraine attack, according to research based on the results of a large clinical trial published in Nature Medicine.
Although there is a paucity of headache studies, the World Health Organisation says about 10-15% of all adults experience migraine, and in Australia, it’s been estimated that migraines affect 5 million people.
The medication, Ubrogepant, is part of a class of drugs that block a key player in migraine pain transmission. While already approved for treating active migraine attacks, its potential to target the prodromal—or pre-headache—phase has remained largely unexplored.
Early symptoms of a migraine can occur hours before the headache itself. For many, it includes an unsettling mix of symptoms: nausea, fatigue, light and sound sensitivity, neck pain, dizziness, and cognitive fog. Some people also experience aura—a visual or sensory disturbance—as a warning sign.
The study evaluated the effectiveness of Ubrogepant in 438 adults aged 18–75 with a history of migraines spanning at least one year. Participants took a 100 mg dose of the drug during the prodromal phase, before the headache had begun.
Results showed that Ubrogepant significantly reduced several early symptoms compared to a placebo. 2 hours after the dose, 19.5% of people showed no photophobia (light sensitivity), compared to 12.5% with placebo. By three hours, 27.3% had no fatigue (vs 16.8%), and 28.9% had no neck pain (vs 15.9%). Four hours after dosing, 50.7% reported no phonophobia (vs 35.8%). The drug also improved cognitive symptoms, with 8.7% reporting no difficulty concentrating at one hour (vs 2.1%), and 56.9% free of difficulty thinking at six hours (vs 41.8%).
The study was welcomed by migraine researchers.
“I think migraine itself is the most neglected, worst managed and least respected medical disorder worldwide,” says Tissa Wijeratne, a distinguished senior neurologist and clinician-scientist, and an advocate for migraine research. He was not involved in this study.
“At this point in time, we have close to 5 million migraine sufferers in Australia. In the world, it is just over 1 billion – so these are scary numbers,” he says. “Most people treat migraine as just a headache. But unfortunately, this is not true. Most of the suffering is not necessarily coming from the headache itself.”
The lead researcher of the Nature paper, neuroscientist Professor Peter Goadsby emphasises that substantial research is still needed to determine optimal treatment strategies for the early, pre-headache stage of migraine.
“Unanswered questions include the locus of the effect of the medicine, which would illuminate understanding of the earliest phases of a migraine attack, the extent to which the findings apply broadly, and larger studies to understand if there are patterns or groups of symptoms that are more likely to respond,” he says.
With migraines afflicting over a billion people worldwide and causing far more than just headache pain, experts warn that rigorous, large-scale research is essential to develop treatments that can interrupt attacks at their very onset.
“The enormity of the problem makes this study huge, despite its just under 500 participants. I think it is setting us in the right direction of where we want to go,” says Wijeratne.
Migraines and the brain
