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Migraine Chronicles, A Revolutionary Approach to Migraine Management

Woman with severe Migraine Headache holding hands to head

A Game-Changer in Migraine Care

In a groundbreaking revelation, recent research has shed light on the revolutionary potential of a specific class of migraine medication, particularly during the prodromal phase. This prodromal phase intervention not only prevents the subsequent headache but significantly reduces its severity, marking a paradigm shift in migraine treatment.

RESOURCED ARTICLE CGRP in Migraine Prodrome Can Stop Headache, Reduce Severity

Migraine Overview

Migraine, a disabling neurological disease affecting over 39 million Americans, goes beyond a severe headache. Recognized by the American Migraine Foundation, its distinctive symptoms demand specialized treatment approaches. These symptoms include intense, throbbing head pain, sensitivity to light, noise, and smells, nausea, and vomiting. The migraine attack comprises four phases: prodrome, aura, headache, and postdrome, with prodrome exhibiting warning signs like extreme tiredness and irritability.


Migraine’s causes remain unclear, but genetics and environmental factors contribute, often running in families. Triggers vary but can include stress, certain foods, hormonal changes, and weather fluctuations. Although it affects diverse demographics, women are disproportionately affected, with hormones playing a significant role.

Diagnosing migraine relies on patient history, symptoms, and a thorough medical examination, as no specific blood test or scan confirms it. Treatments encompass acute and preventive approaches. Acute treatments, administered during an attack, include pain relievers and prescription medications. Preventive treatments aim to reduce attack frequency by utilizing medications, devices, lifestyle adjustments, and behavioral therapies.

Behavioral treatments, like stress management and biofeedback, complement medical approaches, proving effective in reducing attack frequency and severity. The American Migraine Foundation advocates for improved patient lives, offering valuable resources and a Find a Doctor tool to aid in managing this relentless neurological condition.


What are CGRP inhibitors?

CGRP inhibitors, also known as calcitonin gene-related peptide inhibitors, target the small protein CGRP prevalent in sensory nerves supplying the head and neck. Linked to pain transmission, CGRP levels rise during migraines and may contribute to their induction. Two types of CGRP inhibitors exist: monoclonal antibodies (Aimovig, Ajovy, Emgality, and Vyepti) for prevention, administered subcutaneously, and gepants (Ubrelvy, Nurtec ODT, Qulipta, and Zavzpret) that rapidly penetrate the brain for both relief and prevention. While monoclonal antibodies act in the brain lining, gepants, metabolized in the liver, carry a higher potential for interactions and liver damage. CGRP inhibitors, a milestone in migraine prevention, differ from prior agents developed for unrelated conditions.


At the forefront of this discovery is ubrogepant (Ubrelvy), a CGRP receptor antagonist, which has demonstrated its efficacy in the randomized, placebo-controlled crossover PRODROME trial. This trial, conducted across 75 sites in the United States, involved 518 participants with a history of migraine attacks. The participants had a history of two to eight moderate-to-severe headaches per month in the three months leading up to the study.

The prodromal phase, recognized as the earliest stage of a migraine attack.Historically, there has been limited guidance on managing the prodromal phase, with patients advised to prepare for an impending attack rather than actively addressing the prodromal symptoms.

However, the PRODROME trial’s findings have introduced a game-changing approach to migraine care. According to Peter Goadsby, the study investigator and professor of neurology at Kings College London, treating a migraine attack before the headache starts represents a novel strategy. Ubrogepant’s administration during the prodromal phase prevented the development of moderate or severe headaches at both 24 and 48 hours post-dose, showcasing its potential as an early intervention tool.

Unlike traditional acute migraine medications such as triptans, which are not recommended during the prodromal phase, ubrogepant and other members of the “gepant” class demonstrate a different profile. There is no evidence supporting the efficacy of triptans during the prodromal phase, and their use may contribute to medication overuse headaches. In contrast, “gepant” medications, including ubrogepant, appear to lack the propensity for medication overuse problems. Goadsby notes that the more a patient takes “gepant” medications, the less likely they are to experience a headache, highlighting their dual role in both acute treatment and prevention.

The primary endpoint of the trial focused on the absence of moderate- or severe-intensity headaches within 24 hours after the study-drug dose. The results were striking, with a nearly 50% reduction in the incidence of moderate to severe headaches when ubrogepant was taken during the prodromal phase compared to a placebo. This reduction in severity extended to secondary endpoints, including the absence of moderate or severe headaches within 48 hours post-dose and the absence of any headache intensity at 24 hours.

Functional disability assessments also yielded promising results. Participants reported “no disability or being able to function normally” more frequently after treatment with ubrogepant than after placebo, emphasizing the potential impact of early intervention on daily functioning during a migraine episode.

While the study focused on ubrogepants, Goadsby speculates that other members of the “gepant” class may exhibit similar effects. This research not only unveils the acute and preventive capabilities of “gepant” medications but also introduces a new dimension to migraine care—the ability to halt a migraine attack during its prodromal phase.

The prodromal phase, previously underexplored, has gained prominence due to functional imaging studies revealing structural brain changes during this early stage. Goadsby believes that this study initiates a new era of interest, underscoring the clinical value of identifying prodromal symptoms, understanding their characteristics, and exploring effective treatment strategies.

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In conclusion, this research heralds a transformative approach to migraine management. By administering medications like ubrogepant during the prodromal phase, patients may have a powerful tool to not only alleviate the pain associated with migraines but potentially prevent their onset altogether. The implications of this study are profound, offering new hope and possibilities for individuals grappling with the challenges of migraines

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