Migraine Drug Shows Promise in Easing Pre-Headache Symptoms

Ubrogepant, a medication approved for the acute treatment of migraine, has been shown to alleviate several symptoms that can occur before the onset of migraine headaches, according to findings from a phase 3 clinical trial published in Nature Medicine.

The research focused on non-headache symptoms such as nausea, sensitivity to light and sound, dizziness and neck pain that often precede the headache phase of a migraine.

Premonitory symptoms targeted by new trial design

Migraines are typically treated once the headache begins, but many individuals experience early signs that a migraine is imminent. These signs, often referred to as premonitory or prodromal symptoms, may include light and sound sensitivity, nausea, fatigue, neck stiffness and dizziness. Despite their impact on quality of life, few treatments have been assessed for efficacy during this early period.

Researchers led by Peter Goadsby conducted a randomized, double-blind crossover trial involving 438 adults aged 18 to 75 years, each with a history of migraine spanning at least one year. Participants were instructed to take a single 100 mg dose of either ubrogepant or placebo at the first indication of premonitory symptoms, under the condition that they were confident a migraine headache would follow within one to six hours. For a subsequent qualifying migraine episode at least seven days later, participants switched treatments.

Improvement in symptoms observed at multiple timepoints

Participants who received ubrogepant during the early phase of their migraine reported a range of improvements when compared with those who received a placebo. These included:

• Improved concentration one hour after taking the medication.
• Reduced sensitivity to light two hours after dosing.
• Decreased fatigue and neck pain three hours post-dose.
• Reduced dizziness and sound sensitivity between 4 and 24 hours after treatment.

These results suggest that ubrogepant may be effective not only in treating the headache component of migraine but also in reducing the burden of pre-headache symptoms, which can interfere with daily activities.

Need for additional focused research

While these outcomes are promising, the authors noted that further studies specifically designed to evaluate ubrogepant’s impact on premonitory symptoms are necessary. The trial did not include objective measurements of neurological changes during the pre-headache phase, and the primary outcomes relied on self-reported symptom improvements.

Reference: Goadsby PJ, Ailani J, Dodick DW, et al. Ubrogepant for the treatment of migraine prodromal symptoms: an exploratory analysis from the randomized phase 3 PRODROME trial. Nat Med. 2025. doi:10.1038/s41591-025-03679-7

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