February/March 2026 Clinical Research Update: The Latest Findings in Migraine – Part 2

Recent research shows successes and challenges for the migraine field.

Editor’s note: This is Part 2 of MSC’s latest installment of periodic coverage of select new clinical studies in the migraine and headache field. (See Part 1 here.)

Resting-state fMRI in people with migraine
An imaging study published in Neurology looked at how migraine might affect resting-state functional connectivity (rs-FC) – the coordinated neural activity between different brain regions when a person is awake but not performing any specific tasks. To do so, researchers used resting-state functional MRI (rs-fMRI) in a relatively large study, including 264 people with migraine, and 151 age- and sex-matched healthy controls.

Compared to healthy controls, those with migraine showed increased rs-FC between the middle cingulate cortex – a limbic area that plays a role in affective and emotional pain processing – and the occipital cortex and occipital pole (the posterior-most part of the occipital lobe, encompassing the visual cortex), which process visual information.

The group was also interested in learning if rs-FC patterns could differentiate migraine subtypes from each other and from healthy controls, reporting a number of findings in this regard. For instance, the study’s finding of higher rs-FC between the middle cingulate cortex and occipital pole characterized both those who had migraine with aura, and those who had migraine without aura, compared to controls. That also held true when comparing chronic versus episodic migraine, as well as ictal versus interictal migraine, again compared to controls.

The authors stressed that the increased rs-FC between the middle cingulate cortex and occipital pole was the most consistent finding in the study, and that it “might be a disease-specific trait. If this is the case, it might serve as an imaging biomarker of migraine.”

It also points to “a mechanistic relationship between pain networks and visual processing areas” in migraine, with the researchers further saying that the finding “might provide a mechanistic basis for one of migraine’s most defining sensory symptoms, photophobia….[T]he middle cingulate cortex and occipital pole circuit may amplify the salience of visual input, making otherwise innocuous light stimuli perceptually aversive, and in some cases, sufficient to exacerbate or even trigger a migraine attack.”

There were other changes, too. For instance, there was increased connectivity between the limbic lobe and occipital pole and precuneus in those with migraine compared to controls; the precuneus is a key structure in the default mode network involved with integrating different types of sensory input. Those with migraine also showed lower rs-FC between the primary somatosensory cortices and the superior frontal gyrus. And the researchers also drew attention to increased rs-FC between the hypothalamus and precuneus in the ictal migraine group, compared to controls. The authors wrote that, together, these findings point to the involvement of limbic, sensory, and thalamocortical networks in migraine.

The authors cautioned that because the study was a cross-sectional investigation, the findings reflect associations and not necessarily causal relationships. This is a common limitation of imaging studies, and so the authors note that the study leaves open the question of whether the rs-FC patterns discovered in the study increase migraine risk, or instead result from repeated migraine attacks, or might reflect compensatory changes that the brain makes in response to migraine. Only longitudinal studies can answer for sure.

Continuing fruits from OVERCOME
The migraine field continues to see new study results emerging from the well-known ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (OVERCOME [US]) study. OVERCOME is a prospective, longitudinal, web-based survey of US adults with active migraine in the preceding year who were recruited each year from 2018 to 2020. Three recent papers from this initiative provide further understanding of unmet migraine treatment needs, the effects of income and health insurance on migraine care, and why people with migraine are reluctant to take preventive medications.

Unmet migraine treatment needs
First, a recent Headache article presented a pooled analysis of the 2018-2020 cohorts, focusing on the need for initiation/modification of acute or preventive migraine prescription treatment, or both. The study relied on an American Headache Society 2021 consensus statement to determine need.

Roughly 77% of the study’s 59,001 participants were candidates for migraine prescription treatment initiation/modification. Approximately 39% of those had a need for acute prescription medication, 35% had a need for both preventive and acute prescription medication, and about 3% had a need only for preventive prescription medication.

The researchers also used machine learning to identify factors associated with treatment need. Moderate to severe interictal burden, acute medication overuse, and seeing a specialist (neurology/headache specialist/pain specialist) were all strongly associated with acute treatment needs. Acute medication overuse and seeing a specialist were also associated with preventive treatment needs. For the group with both preventive and acute treatment needs, here, too, acute medication overuse, seeing a specialist, and mild to severe interictal burden were significant factors. Migraine-related stigma, and a greater functional impact of migraine, were two additional factors associated with treatment need.

Overall, the results point to the reality that too many people have migraine treatment needs that are not being satisfied.

“[D]espite the resources and focus on migraine education for patients and healthcare professionals prior to and during the time period of the study, there continued to be high unmet treatment needs for individuals with migraine,” as the investigators wrote.

Effects of income and health insurance
In another OVERCOME paper, this time in Advances in Therapy, the topic was how household income affects access to specialty care and use of migraine acute and preventive treatments recommended by the American Headache Society. The study included 56,667 participants grouped into five annual income categories: Less than $25,000, $25,000 to $49,999, $50,000 to $74,999, $75,000 to $99,999, and $100,000 or higher.

The results showed that low income levels are proving a significant barrier to specialty care access and migraine medication use. Considering study participants who sought care in the previous year, a higher proportion of people (roughly 12%) in the lowest income group had emergency/urgent care as their highest level of care, compared to the highest income group (7%). Meanwhile, a greater proportion of those in the highest income bracket (49%) got their highest level of care from specialists, compared to the lowest income bracket (37%) – that translated to those in the highest income group having 40% higher odds of having seen a specialist, compared to the lowest income group.

With regard to health insurance, approximately 60% of the lowest income group had only government-issued insurance, compared to 16% in the highest income group. Further, 19% of the lowest income group had no health insurance, compared to just 4% in the highest income group. Strikingly, those with health insurance were more than two and a half times as likely to have sought care from a specialist, especially those with lower annual income.

As for acute and preventive medication use, the highest income group was 30% more likely to get a recommended acute treatment, and 30% more likely to receive a recommended preventive treatment. Those with health insurance were almost twice as likely to get recommended acute, and preventive, treatment.

Reluctance to take medication
Access to treatment does not mean patients will actually accept those treatments. A third OVERCOME study published in Headache looked to understand why that may be the case.

This secondary post hoc analysis of the 2018-2020 baseline cross-sectional OVERCOME surveys found that while about half of 59,001 participants with migraine had sought migraine care in the previous year, just one-third both sought care and got a diagnosis of migraine, and, strikingly, just 10% sought care, received a migraine diagnosis, and were taking prescription medications to prevent migraine. This failure to complete the care pathway also applied when the researchers broke the results down according to the number of headache days/month. For instance, just 20% of those with more than 15 headache days/month sought care, got a diagnosis, and were taking preventive medication.

The investigators then looked specifically at 22,249 individuals in their sample who were eligible for preventive medication, with eligibility based on the 2021 American Headache Society Consensus Statement, dividing them into those who had ever taken preventives (7,715 “Ever-Takers,” or 35%) and those who had not (14,534 “Never-Takers,” or 65%).

For the Never-Takers, most of the reasons for their decision were medication related, such as concern about side effects (26%), a dislike of taking prescription medications (23%), and a belief that other medications they used were sufficient (21%). Participants also pointed to other issues, including medication access, stigma, and communication between doctor and patient. The investigators also provided detailed data about differences between the Ever-Taker and Never-Taker groups, such as interictal burden and disability.

“[T]his study emphasizes the incredible unmet treatment need in migraine, especially among individuals who are eligible for preventive treatment based on their disease severity and disability,” the authors concluded.

Finishing with some good news
Despite the challenges documented in the OVERCOME studies, the migraine field continues to see positive results from clinical trials. For instance, as documented in an MSC news story, a recent study reported that vaporized cannabis outperformed placebo in reducing pain and other symptoms in people with acute migraine. It turned out that using a 1:2 ratio of THC to CBD was the most efficacious approach, providing a better effect compared to placebo and to either cannabinoid alone.

Monoclonal antibodies targeting the CGRP system have transformed the treatment of migraine for some patients. The key clinical studies of these drugs have focused on adults – but what about kids? In another successful trial (see MSC related news story), researchers found that fremanezumab, an anti-CGRP antibody, worked in the younger population.

This Phase 3, double-blind, multicenter, randomized, placebo-controlled trial, in kids aged 6 to 17 years who had episodic migraine, met its primary endpoint of change from baseline in the average number of migraine days per month, with the fremanezumab group showing a decrease of 2.5 days, compared to a decrease of 1.4 days in the placebo group. Similar positive findings emerged on a number of secondary outcomes. In addition to this favorable study, many other clinical trials of migraine treatments in children and adolescents are underway; see a recent perspective in Headache for more on that score.

Finally, as published in Neurology, a clinical/scientific note reported evidence for the long-term effectiveness of anti-CGRP monoclonal antibodies by assessing patients taking these drugs at a two-year follow-up of the largest prospective multicentric European cohort (known as the EUREkA cohort) assessed thus far.

This observational, registry-based follow-up of chronic and episodic migraine patients taking erenumab, fremanezumab, or galcanezumab reported a median monthly headache day reduction of 10 days, and a reduction of nine monthly migraine days, compared to baseline, in those who reached month 24. Sixty percent of participants showed at least a 50% reduction in monthly headache days at the two-year time point.

In a sub-analysis of patients with data available at six, 12, 18, and 24 months, the study found that just over half of patients showed a sustained response (defined as at least a 50% reduction in monthly headache days for at least three of the four time points); just over one-quarter showed an unsustained response; and about 19% showed no response. Changes in outcome variables improved the most from zero through six months, with no statistically significant results seen from months six to 12, or months 12 to 24.

Finally, by comparing those who reached month 24 of the study to those who discontinued treatment due to a lack of effectiveness, the researchers found that the latter group had higher baseline monthly headache days, as well as more migraine with aura, depression, and obesity.

Neil Andrews is a science journalist and executive editor of the Migraine Science Collaborative.

Image credit: 123RF Stock Photo/ID: 141848843