A year of milestones in headache: Highlights from Headache 2025

The Editors of Cephalalgia, the journal of the International Headache Society (IHS), and Headache, the journal of the American Headache Society (AHS), are collaborating to share some of the most impactful work from 2025 with the readership of the other journal. The goal of this exchange is to foster the broadest possible dissemination of cutting-edge work in headache medicine across the readership of both journals. With this in mind, I am delighted to share with Cephalalgia's readers some of the most outstanding open access manuscripts published in Headache in 2025.

Unsurprisingly, several of the most impactful papers in 2025 were ones that expanded our knowledge of calcitonin gene-related peptide (CGRP)-based treatments.

A common clinical question in tertiary headache clinics is: If the first CGRP pathway monoclonal antibody (mAb) fails to help, does it make sense to switch to another? In a retrospective cohort study, researchers found that switching to another CGRP mAb indeed was useful for at least some patients, bringing them from a median of 27 monthly headache days (MHD) at baseline to 21 MHD at month 3 of treatment with the second mAb (1). Changing the target (CGRP vs. the receptor) did not matter, nor did the number of previous doses of the first mAb. This study provides real-world evidence to support the practice of trying a second CGRP mAb even if the first does not bring benefit.

As the CGRP pathway monoclonal antibodies are still relatively new in the grand scheme of medical practice, post-marketing safety surveillance is critically important. Using a European pharmacovigilance database, authors analyzed all four CGRP mAbs (2). The reported adverse events were generally in line with those already published in the literature, though several hypothesis-generating disproportionality signals were noted.

With all the excitement around CGRP-targeted therapy for adults with migraine, it is critical that these treatments also be studied in children and adolescents for efficacy and safety. To this end, the pharmacokinetics of eptinezumab were recently established in 6–17-year-olds (3). No serious adverse events were noted in the 28 children and adolescents studied. Improvement in migraine-associated disability was observed after a single infusion in both the 6–11 and 12–17-year-old age groups. We now await the outcomes and safety assessments of ongoing randomized, placebo-controlled trials for several CGRP pathway treatments in those under age 18.

Historically, pregnant and lactating women have often been excluded from clinical trials in migraine. Given migraine's epidemiology, this is a major limitation and we need safe ways to gather data in these patient populations. Fortunately, testing of expressed breast milk can safely be done as long as the infant can be bottle fed until the medication is no longer detectable in breast milk. In a study of the pharmacokinetics of ubrogepant in human breast milk, researchers enrolled 12 adult women who were 1–6 months postpartum and provided a single dose of ubrogepant 100 mg orally (4). The cumulative amount of ubrogepant excreted into breast milk over 24 h after dosing was 0.014 mg (i.e., 0.014% of the 100 mg dose). The median time to maximum concentration in breast milk was 1 h. A relative infant dose was calculated based on the maternal data collected (notably not from exposing any infants) and was estimated to be 0.15%. This type of information can allow lactating women and their clinicians to make informed decisions about their migraine treatment.

In addition to learning about new treatments, in 2025 we were still learning new things about old treatments such as triptans. In a population-based study, researchers examined the rate of cardiovascular events in the 90 days after initiating triptan use in adults with migraine (5). After controlling for demographics and cardiovascular risk factors, multivariable analysis showed no association between triptan use and increased risk of cardiovascular events. Authors highlight the importance of considering individual risk factors when making triptan prescribing decisions.

Understanding circadian biology has been of long-standing interest in the field of headache medicine. In a fascinating study examining the role of night shift work on headaches, researchers followed over 500 female hospital employees who worked both day and night shifts (6). They observed that headaches were more likely to occur during night shifts, even after adjusting for multiple other factors, and hypothesized that night shift work may be an independent risk factor for headache. Future research can focus on refining whether people with migraine, tension-type headache or other primary headache disorders are the ones most at risk, and how best to avoid provoking attacks in those whose occupation demands a component of night shift work.

In a real-world evidence study, Terwindt et al. quantified the problem of underdiagnosis of menstrual migraine in clinical practice (7). The study sample contained females aged 18–55 years, of whom 32.3% had a physician-confirmed diagnosis of menstrual migraine. An additional 14.0% self-reported menstruation as a migraine trigger, illustrating how often menstrual migraine may be missed in clinical practice. Moreover, patients with menstrual migraine had higher attack severity and lower acute treatment satisfaction than those without menstrual migraine. Clearly more work is needed to identify patients who have menstrual migraine and to treat their attacks adequately.

The COVID19 pandemic changed the world in countless ways. One important way was how it facilitated broad uptake of telehealth technology. In a new AHS position statement, authors representing the AHS Board of Directors highlighted the importance of continuing support for telehealth in headache medicine, given its demonstrated safety and effectiveness (8). Given the paucity of headache specialists relative to the number of patients needing specialized care, the importance of this issue is obvious, and policymakers should take heed.

“What's going to happen to me?” is a common question patients ask, yet accurate prognostication remains a clinical challenge. Help came from two separate studies this year.

First, in a study of individuals with acute post-traumatic headache, researchers used machine-learning models to predict headache trajectory (9). Participants were asked to keep daily headache diaries. Researchers found that they could identify the mildest trajectory subgroup after only two weeks of headache data collection, and other subgroups after an additional three to five weeks. This work can potentially help plan treatment and identify patients who might need more aggressive early intervention.

In a separate study, researchers examined risk factors for “migraine progression,” while also meaningfully expanding our understanding of that term (10). While traditionally used to refer to progression from episodic to chronic migraine, authors also studied two alternative definitions of migraine progression—an increase of ≥5 migraine headache days (MHD) or an increase of ≥5 points on the Migraine Disability Assessment Scale (MIDAS). Out of those who had episodic migraine at baseline, 4.7% progressed to have chronic migraine at one-year follow-up. However, rates were higher using the alternative definitions of progression: 9.6% progressed using the MHD definition and 21.7% using the MIDAS definition. Across all three definitions, ever having taken preventive medications for migraine was associated with lower odds of progression, while comorbid depression was associated with higher odds. Knowledge of both of these factors provides immediate actionable items for clinicians.

These ten studies represent some of the most exciting and impactful work published in Headache in 2025. By sharing these open access manuscripts with the readers of Cephalalgia, I hope that scientific progress can advance even more quickly. Here's to a prosperous and productive 2026 for both journals, and for our shared field of headache medicine.