Rebecca Erwin Wells

Background: Migraine ranks among the leading causes of disability worldwide. Comorbid depressive symptoms are highly prevalent in patients with migraine and are associated with worsened pain severity, greater migraine-related disability, and poorer migraine prognosis. Despite this burdensome comorbidity, the treatment of these co-occurring disorders has rarely been studied. While mindfulness-based cognitive therapy (MBCT) shows promise for addressing both migraine-related disability and depressive symptoms, its traditional format—8 weekly 2-hour sessions in person—creates substantial access barriers, particularly for patients who experience frequent debilitating migraine and mood symptoms. Objective: The objective of the Treatment for Migraine and Mood (TEAM-M) trial is to evaluate the feasibility of an abbreviated MBCT intervention (MBCT-Brief) delivered via telephone or videoconferencing in adults with migraine and elevated depressive symptoms. Methods: TEAM-M is a 3-site trial with a goal sample size of 145 adults with episodic migraine and elevated depressive symptoms randomized to MBCT-Brief telephone, MBCT-Brief videoconferencing, or enhanced usual care (EUC). To be eligible, participants must meet the criteria for migraine as defined by the International Classification of Headache Disorders 3rd edition, have ≥1 year of migraine history, and have mild to moderate depressive symptoms (scores 5‐19 on the Patient Health Questionnaire-9). Results: Our primary outcomes include treatment feasibility, acceptability, and fidelity. Our secondary outcomes include headache disability, migraine-specific quality of life, and depressive symptoms. This trial was funded in May 2021. We began recruitment in November 2023 and completed enrollment in January 2026. As of May 2026, we have randomized 145 participants, of which 104 have completed the intervention and provided data for our primary outcomes. Data analysis is currently in progress, and primary outcome results are expected to be submitted for publication in spring 2027. Conclusions: The TEAM-M trial addresses a gap in clinical care by evaluating an abbreviated version of MBCT that has scalability and accessibility advantages over full-length MBCT and the potential to address both migraine and depressive symptoms. By reducing the time commitment while maintaining the core MBCT components, MBCT-Brief can potentially address significant access barriers that often prevent patients from receiving evidence-based health care for comorbid physical and mental health symptoms. The remote delivery model offers enhanced scalability. This trial will also yield information about potential differences in telephone versus videoconferencing delivery, which will inform optimal integration into existing primary care and mental health clinic workflows, allowing for improved access to specialized care for mental health and migraine across diverse health care settings.

BACKGROUND Migraine ranks among the leading causes of disability worldwide. Comorbid depressive symptoms are highly prevalent in patients with migraine and are associated with worsened pain severity, greater migraine-related disability, and poorer migraine prognosis. Despite this burdensome comorbidity, the treatment of these co-occurring disorders has rarely been studied. While Mindfulness-Based Cognitive Therapy (MBCT) shows promise for addressing both migraine-related disability and depressive symptoms, its traditional format—8 weekly, 2-hour in-person sessions—creates substantial access barriers, particularly for patients who experience frequent debilitating migraine and mood symptoms. OBJECTIVE The objective of the TEAM-M (Treatment for Migraine and Mood) trial is to evaluate the feasibility of an abbreviated MBCT intervention (MBCT-Brief) delivered via telephone or videoconferencing in adults with migraine and elevated depressive symptoms. METHODS TEAM-M is a three-site trial with a goal sample size of 145 adults with episodic migraine and elevated depressive symptoms randomized to MBCT-Brief telephone, MBCT-Brief videoconferencing, or enhanced usual care (EUC). To be eligible, participants must meet criteria for migraine as defined by the International Classification for Headache Disorders, 3rd Edition, have ≥1 year of migraine history, and have mild-moderate depressive symptoms (score 5–19 on the Patient Health Questionnaire). RESULTS Our primary outcomes include feasibility, acceptability, and fidelity of treatment. Our secondary outcomes include headache disability, migraine-specific quality of life, and depressive symptoms. We began recruitment in November 2023. To date, we have randomized 145 participants, and of these, 81 have completed the intervention. We completed enrollment in January 2026. CONCLUSIONS The TEAM-M trial addresses a gap in clinical care by evaluating an abbreviated version of MBCT that has scalability and accessibility advantages over full-length MBCT and the potential to address both migraine and depressive symptoms. By reducing time commitment and maintaining core MBCT components, MBCT-Brief has the potential to address significant access barriers that often prevent patients from receiving evidence-based healthcare for comorbid physical and mental health symptoms. The remote-delivery model offers enhanced scalability. This trial will also yield information about potential differences in telephone versus videoconferencing delivery that will inform optimal integration into existing primary care and mental health clinic workflows, allowing for improving access to specialized care for mental health and migraine across diverse healthcare settings. CLINICALTRIAL ClinicalTrials.gov NCT05576467. Registered on October 10, 2022.

Objective: Our objective was to develop and assess the effectiveness of a national network of clinicians referring adults with migraine for a remotely delivered clinical trial. Background: A national practice‐based research network in Headache Medicine would facilitate referrals into clinical trials. Given our unique, entirely virtual study, we established a national network of health care professionals to identify potential participants. Methods: The BE WELL with Migraine Champion Providers Network™ began to support clinician referrals across the United States into a remotely conducted clinical trial evaluating the efficacy of a nondrug virtual group intervention. Participant trial recruitment includes community outreach and clinician referrals, then potential participants complete a multi‐step eligibility process. The primary study team obtains informed consent and collects all study outcomes. Clinicians interested in referring patients register for the Network via a Research Electronic Data Capture survey. The ongoing clinical trial allows for recruitment of trial participants and network members through 2026. We analyzed Network survey results through February 25, 2025, with descriptive statistics and qualitative analyses. We compared participant progression through eligibility assessment between clinician referral and community outreach. Results: The BE WELL with Migraine Champion Providers Network™ includes 46 clinicians across the United States through February 2025, and most (89%) of them are headache specialists. Although many have previously served as trial principal investigator (PI) (54%) or recruited (72%) for a trial in the past, 28% are recruiting for a clinical trial for the first time. Top motivating factors for Network participation included nonpharmacological option ( n = 12), research contribution ( n = 11), potential for patient improvement ( n = 11), and working with PI ( n = 9). To date, 905 participants completed the initial online screener, with 5% ( n = 41) from clinician referrals and 95% ( n = 864) from community recruitment. Of those, 12.3% ( n = 107) were eligible to continue and consented and completed the virtual interview. After the interview, 65 participants progressed to the headache log run‐in period and then were randomized/eligible for randomization (six from referrals, 59 from community). Of the original participants from clinician referrals who completed the online screener, 14.6% (six of 41) were randomized/eligible for randomization, compared to 6.8% (59 of 864) recruited via community. Once consented, 100% (six of six) of Network‐referred patients progressed to randomization/eligibility for randomization versus only 58% (59 of 101) from community recruitment. Conclusion: The BE WELL with Migraine Champion Providers Network™ models the development and implementation of a national clinician referring network that can help accomplish the field's research priorities. Although growth and implementation of a national network takes time, our results demonstrate the yield of appropriate referrals eligible for randomization was more than double community recruitment.

Objective: This study was an open‐label single‐arm clinical trial evaluating the fidelity, feasibility, acceptability, and clinical signal of abbreviated mindfulness‐based cognitive therapy (MBCT‐brief) delivered either via telephone (MBCT‐T) or by video conferencing (MBCT‐V) for people with migraine and comorbid depressive symptoms. Background: Migraine is commonly comorbid with elevated depressive symptoms. MBCT reduces depressive symptoms and shows promise to reduce migraine‐related disability. An abbreviated and remotely delivered version of MBCT could increase access to care. Methods: People with migraine and elevated depressive symptoms were recruited from a large urban health system. Participants were assigned in blocks of eight to receive an evidence‐based MBCT‐brief treatment, including eight weekly group classes and home practice delivered via telephone (MBCT‐T) or video (MBCT‐V); MBCT‐T was randomly selected for the first block. Sessions were recorded and coded for treatment fidelity. Feasibility was assessed via session attendance (primary), homework completion, recruitment rate, and survey completion rate. Acceptability was assessed via the eight‐item Client Satisfaction Questionnaire (CSQ‐8; primary), the Credibility/Expectancy Questionnaire (CEQ), the System Usability Scale (SUS), and items assessing survey acceptability. Participants completed the Headache Disability Inventory (HDI) and Quick Inventory of Depressive Symptomatology‐Self Report 16‐item (QIDS‐SR ₁₆ ) at baseline, mid‐treatment, and post‐treatment. Feasibility and acceptability rates were compared to a priori benchmarks. Results: Participants ( n = 16) were all female with a mean (standard deviation [SD]) age of 45 (13) years, the majority of whom identified as White (13/16, 81%) and non‐Hispanic (14/16, 88%). The intervention met the a priori criteria set for therapist fidelity to treatment protocol (mean [SD] MBCT‐Treatment Acceptability and Competence Scale Adherence score 2.9 [0.2]), feasibility (mean [SD] session attendance was 7.9/8 [0.3]), and acceptability (mean [SD] CSQ‐8 score 28.8 [3.3]) for the entire sample and for each treatment arm. The usability of the remote‐delivery system was high across study participants (mean [SD] SUS score 84.8 [11.0]). Survey procedures were broadly deemed acceptable, with at least 80% participants either endorsing “Agree” or “Strongly Agree” across all items. Using Wilcoxon tests, we observed significant reductions in both the HDI (pre‐treatment median [interquartile range] score 63 [40, 70] vs. post‐treatment 36 [26, 54], p = 0.004) and the QIDS‐SR ₁₆ (pre‐treatment median [interquartile range] score 8 [5, 13] vs. post‐treatment 4 [3, 6], p = 0.003). Conclusion: We found that remotely delivered MBCT‐brief for migraine and depressive symptoms was feasible and acceptable to patients in both the telephone and video modalities. Intervention was associated with significant post‐treatment reductions in headache‐related disability and depressive symptomatology, findings that must be interpreted cautiously in the absence of a control group.

Converging lines of preclinical and clinical research indicate that females, in stark contrast to males, display an increased prevalence of chronic pain. Females also demonstrate weaker analgesic efficacy in response to opioid therapies when compared with males. These sex-specific differences may be driven by dimorphic endogenous opioidergic responses. In rodent models, analgesia exhibited in males but not females was reversed by inhibiting endogenous opioidergic reception. In humans, the sex-specific endogenous system(s) supporting the direct attenuation of evoked pain has not been identified. To determine whether opioidergic blockade reverses self-regulated analgesia in males as compared to females, the present study combined two operationally analogous clinical trials (n = 98; 51 females and 47 males). In a double-blinded, counterbalanced study involving healthy (n = 39) and chronic low back pain (n = 59) populations, a high-dose naloxone (μ-, κ-, δ-opioid antagonist) vs. placebo-saline cross-over design (15 mg/kg bolus +0.1 mg/kg/h) tested the hypothesis that endogenous opioids mediate analgesia in males but not females. An 11-point visual analog scale (VAS) (0 = no pain; 10 = worst pain imaginable) evaluated pain ratings in response to noxious heat stimulation (49 °C; calf). After baseline pain testing, participants were randomized to a validated four-session mindfulness meditation or sham mindfulness meditation training intervention. Participants practiced their respective meditation during noxious heat, intravenous high-dose naloxone, and placebo saline, respectively. In males and females, meditation significantly lowered evoked pain during saline infusion. Intravenous naloxone inhibited analgesia in males, but pain relief was well preserved in females. The present findings indicate that endogenous opioids mediate self-regulated analgesia in males but not females and underscore the need to establish sex-specific pain therapeutics.

Objective: To understand the mechanisms of mindfulness' impact on migraine. Background: Promising mindfulness research demonstrates potential benefit in migraine, but no data‐driven model exists from the lived experiences of patients that explains the mechanisms of mindfulness in migraine. Methods: Semi‐structured qualitative interviews were conducted with adults with migraine who participated in two mindfulness‐based stress reduction (MBSR) clinical trials ( n = 43). Interviews were audio‐recorded, transcribed, and summarized into a framework matrix with development of a master codebook. Constructivist grounded theory approach was used to identify themes/subthemes. Results: Participants who learned mindfulness techniques through MBSR experienced altered pain perception, altered response to migraine attacks and disease, increased awareness of external and internal experiences, improved overall well‐being, and group benefits. Mindfulness resulted in earlier stress‐body awareness and increased interoceptive awareness resulting in earlier attack recognition, leading to earlier and more effective management. Interictal factors of self‐blame, guilt, and stigma decreased while migraine acceptance, hope, empowerment, self‐efficacy, and self‐compassion increased. Improved emotion regulation resulted in decreased fear of migraine, pain catastrophizing, anticipatory anxiety, and pain reactivity. Although taught as prevention, mindfulness was used both acutely and prophylactically. We created a conceptual model hypothesizing that MBSR skills led to an infusion of mindfulness in daily life, resulting in altered pain perception and experience, ultimately leading to improvement in overall well‐being, which may positively feed back to the infusion of mindfulness in daily life. The therapeutic benefit of learning mindfulness in a group setting may moderate these effects. Conclusions: This study identified several new potential mechanisms of mindfulness' effect on migraine. After learning MBSR skills, participants reported altered pain and migraine perception and experiences. Increased stress‐body and interoceptive awareness resulted in earlier migraine awareness and treatment. Mindfulness may target important interictal factors that affect disease burden such as fear of migraine, pain catastrophizing, and anticipatory anxiety. This is the first data‐driven study to help elucidate the mechanisms of mindfulness on migraine from patient voices and can help direct future research endeavors.

Objective: This article systematically reviews the empirical literature examining the efficacy of digital headache management interventions for patients with a primary headache disorder. Background: Digital headache management interventions provide opportunities to improve access to behavioral headache interventions to underserved groups. Methods: A systematic search of PubMed, Scopus, and EBSCO (PsycInfo, Education Research Complete, ERIC, Health Source: Nursing/Academic Edition, Psychology and Behavioral Sciences Collection) and reference review was conducted. Included studies had to recruit a sample with a primary headache diagnosis, be a randomized controlled trial including a digital component, assess a headache outcome (i.e., frequency, duration, severity, intensity, disability) or quality of life, and be published in English. Two authors independently extracted data for included studies. The methodological quality of studies was assessed using the revised Cochrane risk‐of‐bias tool. Results: Thirteen studies with unique interventions met inclusion criteria. More than half of the studies were pilots; however, nearly 70% (9/13) demonstrated significant between‐group or within‐group improvements on one or more headache‐related outcomes. All interventions included some form of relaxation training and the majority were delivered via interactive website. While fewer than half the studies report participant race and/or ethnicity, of those that do, 83% (5/6) reported a predominately White/Caucasian sample. Conclusions: Efficacy testing of digital headache interventions is in its infancy with the majority of these studies relying on pilot studies with small samples comprised of homogenous patient populations. Interactive websites were the most common digital medium to deliver digital headache management interventions and have demonstrated promising results. Further testing using large‐scale randomized controlled trials and exploration of other digital tools is warranted. Future studies with more diverse samples are needed to inform health equity of digital headache interventions.