Migraine image generated with GPT-Image-1 (2025, June 24).
For the more than one billion people worldwide living with migraine, the path to effective prevention can feel like an obstacle course. While some migraine patients struggle to find a formal diagnosis, others must navigate a lengthy trial-and-error process with outdated therapies before they can access treatments that provide real relief.
Despite migraine ranking as the second leading cause of disability globally, new patients must undergo a “step-therapy” approach, first trying older preventive medications such as anticonvulsants or antidepressants repurposed for migraine before being granted access to newer, more targeted therapies. This trial-and-error process can lead to significant side effects, limited efficacy and treatment fatigue, leaving some to abandon their search for relief altogether while contributing to the progression from episodic to chronic migraine in some patients. The Cleveland Clinic notes that “ineffective treatment of migraine attacks” is one of the “well-known and established risk factors for migraine transformation” from episodic to chronic.
New data from a head-to-head study is challenging the long-standing treatment paradigm. The TEMPLE study, released during Migraine & Headache Awareness Month, compared atogepant (Qulipta/Aquipta), a once-daily oral medication specifically designed for migraine prevention, against topiramate, the most frequently prescribed traditional preventive. The results were clear: patients taking atogepant were 59% less likely to discontinue treatment resulting from side effects compared to those on topiramate, and nearly two-thirds achieved meaningful reductions in monthly migraine days versus just 39% on the older medication.
To understand what these findings mean for patients and the future of migraine care, Drug Discovery & Development spoke with Jaclyn Duvall, MD, a neurologist and founder of Headache Specialists of Oklahoma, and Karen Carr, Ph.D., Scientific Director for Migraine in International Medical Affairs at AbbVie.
Dr. Duvall serves on the speakers bureau for Abbvie/Allergan, BioDelivery Sciences, Biohaven, Eli Lilly, Impel, Teva, and Lundbeck. She has also served as a consultant for Abbvie/Allergan, Biohaven, Impel, and Teva.
Beyond traditional preventives
Dr. Jaclyn Duvall
Dr. Duvall doesn’t mince words about the current state of migraine prevention. “Traditional oral preventive medications, including beta-blockers and tricyclic antidepressants, have substantial drawbacks that include limited efficacy, delayed onset and high rates of side effects,” she explains. Yet despite these limitations, providers are often required to prescribe them first due to insurance step therapy requirements. This creates a frustrating cycle where patients, who may not understand the insurance-driven restrictions, experience “trial-and-error fatigue” and often discontinue treatment before seeing any benefit.
The TEMPLE study specifically compared atogepant against topiramate: the most frequently prescribed traditional migraine preventive. While Dr. Duvall notes that topiramate typically offers “higher odds of successful treatment” compared to beta-blockers or tricyclic antidepressants, she emphasizes a fundamental limitation: “Because these medications weren’t designed specifically for migraine, we see limited precision and tolerability.”
“One of my biggest concerns is because of prior experience, including stigma, lack of disease awareness/education, and traditional preventive medication failures, many patients no longer seek care from a neurologist for migraine,” Duvall notes. She hopes studies like TEMPLE will “raise awareness, cut down on step-therapy requirements and help educate providers and patients” to more effectively manage migraine.
Karen Carr frames the TEMPLE study thusly: “It is a study we at AbbVie designed thinking of the person with migraine who deserves to get their time back, someone who deserves access to migraine treatments that actually target their disease.” Carr says the results of the TEMPLE study “directly challenge the status quo in migraine care.” That is, it demonstrated that atogepant, a migraine specific treatment, can provide superior preventive efficacy to repurposed treatments.
Choosing the right CGRP treatment
With both oral CGRP antagonists (gepants) and injectable CGRP monoclonal antibodies available, clinicians now have options to match treatment to patient preferences and needs. Dr. Duvall identifies several factors that might make oral medications the better choice: “women of childbearing age (gepants can be discontinued quickly if pregnancy is desired), concern about committing to long-acting medications, those with needle phobia.”
As Carr emphasizes, “Migraine is experienced and lived individually. Every patient should be able to access a treatment uniquely suited to their needs.”
Transitioning patients
When it comes to switching patients from older preventives to atogepant, Dr. Duvall notes that approaches “will differ considerably amongst healthcare providers.” In her practice, she tailors the transition based on the patient’s current experience.
For patients who have found some benefit from their current medication and tolerate it well, she may layer atogepant on top, allowing “4-8 weeks of concomitant treatment” before beginning to taper off the older preventive. However, if a patient has experienced intolerable side effects or lack of efficacy, she takes a different approach: discontinuing the older medication (with appropriate tapering if needed) and starting atogepant immediately, with “no washout period needed.”
Why CGRP antagonists don’t cause medication overuse
One of the most significant advantages of CGRP receptor antagonists is their ability to avoid the medication overuse headaches that plague many migraine treatments. Dr. Duvall explains the mechanism: “Simply put, CGRP receptor antagonists are disease-modifying. While triptans and pain medications can enhance pain pathways, CGRP receptor antagonists disrupt the underlying pathophysiology, potentially reducing central sensitization over time.”
Carr provides additional scientific context: “the oral CGRP receptor antagonists, or gepants, are not believed to be associated with sensitization or changing the way the nervous system communicates when pain signals are processed.” Some of this understanding derives from experiments using ubrogepant, which is an FDA-approved approved acute treatment for migraine. Ubrogepant “demonstrated a lack of central sensitization after repeated exposures in a pre-clinical model of medication overuse headache,” Carr said. “Additionally, we have data from atogepant preventive clinical studies showing that more people taking placebo increase their days with headache than when on atogepant.”
While the safety information mentions concerns about high blood pressure and Raynaud’s phenomenon, Dr. Duvall’s clinical experience is reassuring: “I have not seen any patients with either of these concerns.” She continues to inform patients about these “rare, but potentially serious side effects” as part of standard counseling.
Expanding access and understanding
While data on atogepant use in elderly patients and those with multiple comorbidities remains limited from clinical trials, Dr. Duvall notes that “early real-world evidence suggests it remains well-tolerated and effective in these populations.”
Carr acknowledges that while the TEMPLE study and Phase 3 preventive treatment studies included adults up to age 80, they weren’t specifically designed to demonstrate efficacy in this population. “There is still much work to be done to understand the true impact of migraine severity in all people with migraine and to advance education in this space,” she says. “We are committed to continuing to grow our knowledge of migraine.”
Filed Under: Neurological Disease
