A migraine drug called ubrogepant doesn't just reduce the severity of a migraine attack – it also dials down the non-headache symptoms in the prodrome: the hours leading up to the main event.
That's the conclusion reached after a large clinical trial tested hundreds of migraine patients taking the medication at the onset of prodrome symptoms.
The result suggests that ubrogepant might be effective for treating the entire migraine as it evolves, rather than just the head pain – and narrows down the mechanisms behind the condition.
Migraine is a neurological affliction that affects an estimated 14 to 15 percent of the global population, yet it remains poorly understood, and difficult to treat effectively. It's known for its searing, debilitating head pain, but the anatomy of a migraine is much more complex and longer-lasting than just the head pain.
Broadly, a migraine consists of three to four stages: the prodrome, during which the patient experiences symptoms such as light sensitivity, nausea, neck pain, and brain fog; aura, characterized by vision disturbances, including blind spots and flashing lights; the headache attack itself; and the postdrome, characterized by brain fog and fatigue.
Put together, this sequence of events can last up to more than a week. It's quite unpleasant.
Most treatments focus on the headache portion, since it's the most debilitating. Even studies on treatments designed to be taken during the prodrome phase have concentrated on blocking the headache, rather than treating the prodrome itself.
Led by neurologist Peter Goadsby of Kings College London, a team of researchers has now conducted a trial on whether or not ubrogepant, a migtainte treatment available in the US under the brand name Ubrelvy, also works on the prodrome.
Scientists want to know not just how to treat the entirety of a migraine – although that's a desired goal – but to help determine what drives a migraine attack.
"It has long been argued whether migraine is primarily a disease of the brain or of peripheral, specifically vascular, origin," the researchers write in their paper. "The new data firmly support a brain origin for migraine attacks."
Ubrogepant is a drug that does not prevent migraine attacks, but reduces the severity of the pain associated with an attack. It belongs to a class of drugs called calcitonin gene-related peptide (CGRP) receptor antagonists. Ubrogepant, and other drugs belonging to the same class, block the action of CGRP, a peptide associated with migraine.
Goadsby and his colleagues recruited hundreds of migraine patients for a double-blind study. The 438 study participants, aged between 18 and 75, and all with at least a one-year history of migraine, were put in groups.
One group was given ubrogepant at the onset of prodrome symptoms; the other was given a placebo. Then, during a second event at least seven days later, the groups switched. The patients initially given the drug were given the placebo, and vice versa. Neither the researchers nor the participants knew which group was receiving which.
After taking the drug or the placebo, the participants were tasked with reporting changes in their symptoms, which included photo- and phonophobia, dizziness, fatigue, neck pain or stiffness, and brain fog. The patients taking the drug experienced a significantly higher reduction in their symptoms than the patients taking the placebo.
One hour after taking ubrogepant, patients reported brain fog easing. After two hours, photophobia, or sensitivity to light, decreased. After three hours, neck problems eased. Between four and 24 hours after taking the drug, phonophobia (sensitivity to sound) and dizziness lessened, too.
These results suggest that CGRP receptor antagonists might be effective at treating prodromal migraine symptoms, the researchers say.
"As premonitory symptoms can be disabling, their treatment alone is clinically relevant, beyond the consideration that treatment during the prodrome prevents headache onset and improves function over 24 to 48 hours, as demonstrated in the primary analysis of the study," the researchers write.
In addition: "Broadly, the findings of the clinical trial support imaging studies that have identified central nervous system sites as the locus of initiation of a migraine attack."
There are several routes forward from here. The study didn't look at the effects of ubrogepant on the aura and postdrome phases of migraine, which could warrant further investigation.
Future work could also probe further to try and narrow down the cause of migraine, and determine whether CGRP receptor antagonists might offer relief for the entire course of a migraine event.
The research has been published in Nature Medicine.