Migraine isn’t simply a “bad headache” — it’s a complex neurological disease that can affect your entire brain and body before, during, and after the painful headache attack.
Since 2018, several new migraine-specific treatments have been approved in the United States and elsewhere. New research suggests that one of them, ubrogepant (Ubrelvy), not only may help people stop a migraine attack from happening when it’s used before the pain begins, but also may alleviate some of the early symptoms altogether as soon as an hour after taking it.
Subtle Migraine Symptoms in the Prodrome Phase
A migraine attack is a complex neurological event with several phases:
- The prodrome (or premonitory phase), which begins up to one to two days before the onset of headache pain
- The aura phase, which starts about an hour before the onset of pain (some migraine patients experience the aura phase regularly, some get it only occasionally, and some never have it)
- The headache phase
- The postdrome or “hangover” phase after the pain recedes
Common prodrome symptoms include:
- Excessive yawning when you don’t feel unusually tired
- Neck soreness
- Sensory hypersensitivity: Lights feel too bright, sounds seem too loud, scents seem too strong
- Fatigue and lethargy (lack of energy)
- Difficulty concentrating
- Frequent urination
- Food cravings
- Generalized irritability and other mood changes
Ubrelvy Stops Attacks for Nearly Half of Users When Taken Early
About 500 people in the United States participated in the placebo-controlled, double-blind, randomized study from 2020 to 2022. They had an average of two to eight migraine attacks per month and could reliably predict many attacks based on their prodrome symptoms.
Study subjects took their medication when they experienced two prodrome symptoms and were confident that they would have a headache within one to six hours. One group of subjects took 100 milligrams (mg) of Ubrelvy at the first prodrome symptom and a placebo at the second; the others took the placebo at the first prodrome symptom and Ubrelvy at the second.
- 46 percent of subjects who took Ubrelvy first said it prevented moderate-to-severe headaches for 24 hours after using the medication, compared with 29 percent of those who took the placebo first.
- 41 percent of subjects in the Ubrelvy-first group said it prevented moderate-to-severe headaches for 48 hours after using the medication, compared with 25 percent of those in the placebo-first group.
- 24 percent of subjects in the Ubrelvy-first group said they experienced no headache symptoms at all for 24 hours after using the medication, compared with 14 percent in the placebo-first group.
- Subjects in the Ubrelvy-first group were more likely to report they could function normally in the 24 hours compared with the placebo-first group.
“The PRODROME study shows that in people who know when an attack is coming, if they treat BEFORE headache begins, they can prevent their headaches, shorten the duration of their warning symptoms, and improve their function,” says Richard B. Lipton, MD, professor and vice chair of neurology at Albert Einstein College of Medicine in New York, director of the Montefiore Headache Center, and primary author of the PRODROME study. “We know this approach works for gepants. We suspect it does not work for triptans.”
Ubrelvy Also May Ease Nonheadache Symptoms
In the study, the most common prodromal symptoms identified were:
- Photophobia (light sensitivity)
- Fatigue
- Neck pain/stiffness
- Phonophobia (sound sensitivity)
- Cognitive impairment (brain fog)
- Dizziness
In this trial, 31.7 to 57.2 percent of these premonitory symptoms were moderate to severe in intensity and associated with functional disability.
Photophobia was the most commonly reported early symptom, present in about 61 percent of the attacks in the study. After treatment with 100 mg of Ubrelvy, it appeared to resolve as early as two hours later and continued past the 48-hour mark.
Difficulty concentrating, part of what many describe as brain fog, also appeared to resolve within an hour of taking Ubrelvy, and continued to 24 hours postdose.
The symptoms of fatigue, neck pain, and phonophobia also showed significant reductions postdose.
However, Ubrelvy seemed to have limited impact on dizziness, which was present in about 30 percent of the attacks in the study.
It has long been argued whether migraine is primarily a disease originating in the brain or if it has a vascular origin. The new data supports the brain origin theory, given that both symptoms and functional imaging studies implicate brain regions in the earliest phase of a migraine attack.
Nearly 3 Out of 4 Users Experienced No Migraine-Related Disability After Taking Ubrelvy
- 65 percent of Ubrelvy first users reported that they experienced mild to no limitation on their typical daily activities 24 hours after medication, compared with 48 percent of placebo first users.
- As early as two hours after taking medication, subjects who took Ubrelvy first were 73 percent more likely to report having “no disability, able to function” compared with those who took the placebo first.
“Finally, we have a treatment that works when used during prodrome,” says Jessica Ailani, MD, professor of clinical neurology at MedStar Georgetown University Hospital in Washington, DC, and director of the MedStar Georgetown Headache Center. “By the time we saw the study results, we were already getting the sense that this was working in clinic, but to have this proved in a trial setting was very important.”
How Ubrelvy Works: Mechanism and Benefits
Ubrelvy is an oral medication approved in the United States for acute treatment of migraine, which means that you take it to treat an attack when you notice symptoms. It’s one of several new medications called gepants, short-acting treatments that block the action of calcitonin gene-related peptide (CGRP), a protein involved in the migraine process.
If CGRP can’t bind to its receptors along nerves in the head and face, it can’t trigger the increased pain signals, inflammation, and other responses that lead to the headache phase of an attack.
The other gepants approved for use in the United States are:
- atogepant (Qulipta), an oral medication for the prevention of episodic and chronic migraine
- rimegepant (Nurtec ODT), a dissolving oral tablet for acute treatment of migraine and preventive treatment of episodic migraine
- zavegepant (Zavzpret), a nasal spray for acute migraine treatment
Gepants may be safer than triptan medications (the longtime gold standard for acute migraine treatment) for people with high blood pressure and other risk factors. They may be effective for the estimated one-third of people with migraine who don’t get relief from triptans. And unlike triptans, gepants don’t seem to contribute to the risk of medication overuse headache (MOH) or “rebound headache,” a vicious cycle of worsening headache attacks caused by frequent use of certain acute treatments.
What the Ubrelvy PRODROME Study Means for People With Migraine
Symptom Tracking Can Help You Treat Attacks Early
Tracking your symptoms regularly can help you see patterns you might not notice in your daily life — like what your prodrome symptoms are. You can make more effective decisions about treating attacks when you recognize the early signs that an attack is coming, regardless of which treatment you use.
“Prodrome is very disabling to most patients, [and] I don't think I realized this at all prior to the study,” says Dr. Ailani. “While prodrome is so varied in patients, there are some symptoms that are most common — photophobia being the most common experienced prodrome in this study — this can help us in clinic when starting a conversation about prodrome with patients.”
Headache Experts Are Still Discovering New Ways to Manage Migraine Effectively
“The findings teach us how gepants can work in any part of the migraine cycle — so early you can treat at the onset of migraine (prodrome for up to 60 percent of patients), and used often they can be preventive of migraine (as we see in studies looking at rimegepant and atogepant),” says Ailani. “Studies evaluating triptans during prodrome did not prove successful, so we really are seeing here what makes gepants special more so than learning more about migraine pathophysiology.”
Don’t Believe Everything You See in Those TV Ads for Migraine Meds
The TV commercial suggested that Ubrelvy eliminated migraine pain and symptoms far more rapidly than shown in clinical trials. AbbVie said it has stopped using the commercial.
Although the FDA’s action doesn’t take away from the Ubrelvy PRODROME study’s promising results, it’s a good reminder that distinguishing good news from misleading information isn’t easy. Your best friend may swear a certain treatment “works like magic” for them, but that doesn’t mean it’s magical (or effective or even safe) for everyone.
Even promising clinical trial results don’t apply to everyone equally. When in doubt, talk to your healthcare provider.
Final Thoughts
The PRODROME study suggests that Ubrelvy may help people with migraine stop a moderate-to-severe attack if they take it when they notice prodrome symptoms, up to six hours before the headache phase begins. People in the study who took Ubrelvy at the first sign of prodrome symptoms experienced much less disability from migraine attacks than people who took the placebo first.
A later analysis of the study showed that some of the most common prodromal symptoms, like light and sound sensitivity, brain fog, and neck pain, can be alleviated altogether when treated with Ubrelvy before the head pain even begins. For some people, these symptoms can be just as disabling, so these findings give new hope for more functional days.
The study reinforces what many headache experts have noticed in practice about the effectiveness and versatility of gepants, a new class of migraine medications used for acute and preventive treatment.
Although no single migraine treatment is safe or effective for everyone, the Ubrelvy PRODROME study offers encouraging news for people with predictable prodrome symptoms who want to reduce the burden of migraine attacks on their ability to function normally. If you’re interested in trying this approach with your migraine attacks, talk to your healthcare provider.