Background: Migraine is a disabling neurovascular disorder that may evolve from episodic to chronic forms, often complicated by medication-overuse headache (MOH). It generates substantial healthcare expenditures and indirect societal costs. Pharmacological constraints and resistance to acute therapies contribute to the development of MOH and increase the need for preventive treatments such as onabotulinumtoxin A (BoNT/A) and monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. Objective: This pharmacoepidemiology retrospective study aimed to evaluate real-world prescription patterns of BoNT/A and anti-CGRP/R mAbs in an Italian regional setting and to compare current data (2023–2024) with previously observed patterns (2020–2022) before the integration of pharmacists as outpost in migraine man-agement. Methods: Anonymized data were obtained from the regional drug reimbursement and prescription database. Results: A total of 9,012 and 9,705 prescriptions were recorded in 2023 and 2024, respectively, indicating an increasing trend in the use of innovative preventive therapies. A gradual increase in the use of eptinezumab and BoNT/A appears to be associated with regional organizational measures aimed at improving access to care, adherence to clinical guidelines, and integrated management across healthcare levels. Conclusion: Therapeutic appropriateness is far from reaching the gold standard and an increasing role of pharmacists could improve clinical outcomes.

Cerebral venous thrombosis (CVT) predominantly affects young adults and frequently presents with headache. Although functional outcomes are generally favorable, many patients report persistent or recurrent headache long after the acute event. This systematic review aimed to assess the prevalence, clinical characteristics, associated factors, and management of long-term headache following CVT. A systematic search of PubMed and Embase (2000-2025) identified studies reporting original data on long-term headache after CVT in adult populations. Case series including fewer than 30 patients were excluded. Given substantial heterogeneity in study design, definitions, and outcome measures, a qualitative synthesis was performed. Fifteen studies including 2,136 patients were analyzed. The reported prevalence of post-CVT headache ranged from 14% to 59%. Headache most often resembled primary headache disorders, particularly tension-type and migraine-like phenotypes. Available data suggest that de novo headache may represent the most frequent presentation, although modification of pre-existing headache disorders also occurs. Pre-existing headache and depression were associated with post-CVT headache, whereas intracerebral hemorrhage was not. Associations with venous recanalization, thrombosis location, and anticoagulation delay were inconsistent. Secondary mechanisms, including intracranial hypertension, dural arteriovenous fistula, CVT recurrence, and medication-overuse headache, were identified in some patients. Data on management strategies were limited. Long-term headache is a frequent but under-recognized complication of CVT that may significantly impact quality of life. The absence of a standardized definition contributes to heterogeneity across studies. After exclusion of secondary causes, post-CVT headache encompasses both de novo and modified primary headache phenotypes. A consensus term such as "new or modified recurrent headache attributed to past CVT" may help describe this spectrum and improve clinical characterization and future research.

Migraine is a prevalent chronic neurovascular disorder characterised by recurrent episodes of moderate-to-severe headache, frequently accompanied by nausea, vomiting, photophobia, and phonophobia, and it substantially impairs quality of life. Migraine is broadly categorised into migraine with aura and migraine without aura, while diagnosis depends primarily on clinical history, symptom assessment, and the International Classification of Headache Disorders guidelines. Conventional pharmacological therapies, including ergot alkaloids, analgesics, triptans, calcitonin gene-related peptide antagonists, beta-blockers, and antidepressants, are widely used for acute and preventive migraine management. However, prolonged use of these synthetic agents is commonly associated with adverse effects such as gastrointestinal disturbances, cardiovascular complications, dizziness, and medication-overuse headache. This narrative review evaluates the therapeutic potential of medicinal plants and their bioactive phytoconstituents in migraine management. Data were collected from Scopus, PubMed, ScienceDirect, Web of Science, Scientific Electronic Library Online, Google Scholar, JSTOR, Springer Link, Oxford University Press, MDPI, and Taylor and Francis Online. The reviewed literature indicates that selected medicinal plants may influence migraine-related pathways through modulation of neuroinflammation, oxidative stress, neurotransmitter imbalance, nociceptive signalling, and vascular dysfunction. Key phytoconstituents discussed include parthenolide from Tanacetum parthenium, petasin and isopetasin from Petasites hybridus, valerenic acid from Valeriana officinalis, linalool from Lavandula angustifolia, and withanolides from Withania somnifera. These compounds are reported to exhibit anti-inflammatory, antioxidant, neuroprotective, vasorelaxant, and neuromodulatory activities. Overall, medicinal plants may offer complementary, multitargeted options for migraine management. Nevertheless, the limited availability of large-scale, well-controlled clinical trials restricts definitive conclusions regarding their long-term efficacy, safety, dosage standardisation, and integration with conventional therapy.

Chronic migraine (CM) carries high disability, yet interictal MRI phenotypes that distinguish CM from episodic migraine (EM), particularly in medication-overuse headache (MOH)-inclusive cohorts, remain incompletely characterized. We tested whether periventricular diffusivity (PVeD), an indirect MRI marker of tissue-water properties at the ventricular-parenchymal interface, is associated with CM and headache burden. In this cross-sectional 3.0-T multimodal MRI study, 289 adults with complete structural MRI, diffusion MRI, and resting-state fMRI were analyzed: 67 healthy controls, 162 EM, and 60 CM. MOH was diagnosed and retained in the CM group. MRI was acquired during verified interictal evening sessions; participants with headache within 24 hours before or after MRI were excluded. The primary contrast was age- and sex-adjusted CM versus EM for PVeD. Secondary analyses examined MOH strata, headache-frequency strata, partial Spearman correlations, Firth logistic regression for CM status, and HIT-6 models. Age- and sex-adjusted PVeD was lower in CM than EM (adjusted difference, -0.011; 95% CI, -0.017 to -0.006; standardized difference, -0.71; p < 0.001) and healthy controls (-0.014; 95% CI, -0.021 to -0.007; standardized difference, -0.88; p < 0.001), with no EM-control difference. Both CM participants with and without MOH had lower PVeD than EM. In migraine participants, lower PVeD correlated with higher headache frequency, HIT-6, and MIDAS and with larger choroid plexus volume and smaller thalamic, nucleus accumbens, and putaminal volumes. In the expanded clinical-plus-MRI Firth model, each 1-SD higher PVeD was associated with lower CM odds (OR, 0.59; 95% CI, 0.38 to 0.89; p = 0.011). Higher PVeD was associated with lower HIT-6 after adjustment for headache frequency or MOH. CM was associated with lower PVeD at the ventricular-parenchymal interface, and lower PVeD was linked to patient-centered burden in this MOH-inclusive cohort. PVeD is not yet a diagnostic or treatment-selection biomarker, but may help define an MRI phenotype for future chronification-risk and treatment-response studies after longitudinal and external validation.

BackgroundThe phase 4 RESOLUTION trial showed that the first 12 weeks of treatment with eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduced migraine frequency, severity, and disease burden, and improved quality of life (QOL) versus placebo in participants with chronic migraine (CM) and medication-overuse headache (MOH) who also received patient education. Here, we present 24-week eptinezumab efficacy and safety in the RESOLUTION trial.MethodsRESOLUTION was a randomized, parallel-group, multinational clinical trial that included a 12-week double-blind, placebo-controlled period and a 12-week open-label extension period (OLE). Adults (18–75 years) with CM and MOH (excluding opioid-overuse headache) received a brief educational intervention about MOH at baseline and were randomized (1:1) to IV eptinezumab 100 mg or placebo. At Week 12, all participants received eptinezumab 100 mg. Measures used for primary and key secondary efficacy endpoints were also captured during the OLE: mean changes from baseline in monthly migraine days (primary endpoint: Weeks 1–4), monthly headache days, monthly days with acute medication use, average daily pain, and participants no longer meeting threshold criteria for CM nor MOH. Secondary endpoints (including patient-reported-outcomes [PROs] assessing disease-related burden and health-related QOL) and treatment-emergent adverse events (TEAEs) were also captured during the OLE.ResultsOf 608 participants randomized, 593 (97.5%) were treated with eptinezumab in the OLE, and 584/608 (96.1%) completed the trial. Reductions in migraine frequency and active CM/MOH diagnosis, and improvements across multiple PROs observed in post hoc analyses during the placebo-controlled period were sustained during the OLE for participants initially treated with eptinezumab, with similar levels of improvement gained for those initially receiving placebo. The proportion of participants with TEAEs in the OLE was similar between eptinezumab–eptinezumab and placebo–eptinezumab treatment sequence groups (30% vs 34%); no new safety signals were identified.ConclusionsIn participants with CM and MOH who received patient education, reductions in disease burden and improvements in QOL during the first 12 weeks with eptinezumab treatment were sustained for up to 24 weeks following a second eptinezumab infusion, with similar improvements observed in participants switched from placebo to eptinezumab. Eptinezumab was generally well tolerated, with no new safety signals.Trial registrationClinicalTrials.gov Identifier: NCT05452239 (https://clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40)Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-026-02423-x.

BackgroundThe Delta-opioid receptor (DOR) has gained attention as a promising target for the treatment of migraine and headache disorders. This is largely attributed to its unique pharmacological profile, which suggests that DOR-targeting treatment offers effective therapeutic benefit with a lower risk of medication overuse headache (MOH), reduced abuse liability, and minimal potential for physical dependence. These advantages have driven the development of a novel DOR agonist PN6047 (3-[[4-(dimethylcarbamoyl) phenyl]-[1-(thiazol-5-ylmethyl)-4-piperidylidene] methyl]benzamide), which has completed Phase I clinical trial and showed a favorable safety and tolerability profile. Although PN6047 has shown promising effects in neuropathic pain models, its efficacy in preclinical models of headache-associated pain remains to be evaluated. Here, we investigated the effects of PN6047 in models of migraine-associated pain and aura as well as post-traumatic headache (PTH) and MOH.MethodsC57BL6/J mice were used to examine the effects of PN6047 in the following migraine models: chronic intermittent nitroglycerin (NTG)-induced migraine-associated pain, PTH, KCl-induced cortical spreading depression (CSD), and optogenetic evoked CSD in a freely behaving transgenic mice expressing ChR2-eYFP. In addition, we tested whether chronic PN6047 induced MOH and whether it could prevent the development of MOH induced by sumatriptan.ResultsA single injection of PN6047 blocked chronic cephalic allodynia established by chronic intermittent NTG and PTH. Moreover, chronic PN6047 treatment prevented the development of MOH induced by sumatriptan, without causing MOH itself. In addition, PN6047 significantly reduced the number of CSD events in the KCl-induced CSD model, and delayed CSD onset triggered in freely behaving mice along with subsequent CSD-evoked allodynia.ConclusionPN6047, a novel DOR agonist, strikingly blocks headache-associated mechanism and symptoms in preclinical models of chronic migraine, migraine aura, PTH, and MOH. Importantly, prolonged PN6047 treatment did not induce MOH or analgesic tolerance. Together, these data demonstrate that despite the distinct mechanisms underlying migraine and headache disorder, PN6047 exhibits robust efficacy without inducing MOH, and displays a favorable safety and tolerability profile.

Migraine is acommon neurological disorder that affects about 10% of children and adolescents and is associated with reduced school performance and participation in everyday life. The highest incidence of migraine occurs between 10-14years. With the onset of puberty, girls are increasingly more likely to be affected. Generally, girls in all age groups show ahigher prevalence and incidence of migraine, in contrast to tension-type headaches, where gender differences are less pronounced. Girls experience higher levels of migraine-related impairment than boys and are more likely to have comorbid mental health conditions. School-related stress and performance pressure are described primarily by girls as migraine triggers. Gender differences in epidemiology and clinical features have been widely studied in adulthood. Nevertheless, only afew studies deal with gender-specific treatment in childhood and adolescence. In addition to acute pain treatment while avoiding medication overuse, an individualized and multimodal headache therapy is the most important treatment component for recurrent headaches in childhood. Interdisciplinary group therapies enable individualized care for gender-specific circumstances.

Calcitonin gene-related peptide (CGRP) is a key mediator in migraine pathophysiology, and the development of gepants, novel CGRP receptor antagonists, has expanded therapeutic options for both acute and preventive treatment. This scoping review aims to synthesize current evidence on the pharmacology, clinical applications, safety, and combination strategies of gepants. A scoping review was conducted following PRISMA-ScR recommendations. A comprehensive search of PubMed/MEDLINE and Scopus was performed from database inception to July 2025, with an additional search in January 2026 for real-world studies. Data were extracted and summarized narratively without quantitative synthesis. Second- and third-generation gepants, including ubrogepant, rimegepant, atogepant, and zavegepant, overcome the hepatotoxicity and bioavailability limitations of earlier compounds. Pharmacokinetic properties determine their suitability for both acute and preventive use, and their lack of vasoconstrictive activity makes them suitable for patients with cardiovascular comorbidities. Most are metabolized by cytochrome 3A4 and are substrates for efflux transporters, necessitating awareness of drug-drug interactions, although no clinically significant interactions with common migraine preventive medications have been reported. Preclinical and preliminary clinical evidence indicates a low likelihood of gepants inducing medication-overuse headache. Combination therapy with other migraine treatments is mechanistically plausible and supported by early pharmacokinetic and safety data, though robust clinical trial evidence remains limited. Gepants represent an effective and well-tolerated class of CGRP-targeted therapies with flexible use in acute and preventive migraine management. Their pharmacological properties support individualized treatment strategies and potential combination approaches; however, long-term safety, optimal positioning, and the efficacy of combination regimens require further investigation.

We hypothesized that sustained astrocyte activation in the trigeminal nucleus caudalis (TNC) drives prolonged hyperalgesia in triptan-induced medication-overuse headache (MOH). This study aimed to investigate the role of astrocyte activation and evaluate the therapeutic potential of targeted astrocyte inhibition. Chronic triptan use for migraine can lead to MOH, characterized by persistent hyperalgesia and high relapse rates. The mechanisms underlying this transition remain poorly understood. Although central sensitization and neuroinflammation are implicated, the specific contribution of astrocytes in TNC has not been investigated. A rat MOH model was established by repeated intraperitoneal administration of sumatriptan for 9 days. Cutaneous allodynia was assessed using von Frey filaments, and latent sensitization was evaluated under the 0.5 mg/kg nitroglycerin challenge. To selectively inhibit astrocyte activation, an adeno-associated virus vector was injected into bilateral TNC, followed by the administration of its ligand, deschloroclozapine. Neuronal (cellular proto-oncogene Fos, calcitonin gene-related peptide, postsynaptic density protein 95, and synaptophysin), microglial (ionized calcium-binding adapter molecule 1), and astrocytic (glial fibrillary acidic protein) markers, along with proinflammatory mediators (inducible nitric oxide synthase, tumor necrosis factor-alpha, etc.), were analyzed via immunofluorescence and Western blot. Repeated sumatriptan induced long-term cutaneous allodynia and latent sensitization. This process was accompanied by transient activation of neurons and microglia, and a short-term increase in synaptic proteins and proinflammatory cytokines in TNC. However, astrocyte activation sustained after the behavioral hypersensitivity had apparently resolved. Chemogenetic inhibition of astrocytes in TNC prevented the development of long-term cutaneous allodynia and latent sensitization. This intervention also ameliorated the overexpression of synaptic proteins and proinflammatory cytokines. Our findings demonstrate that sustained astrocyte activation in TNC is a potential driver of prolonged hyperalgesia in triptan-induced MOH. Inhibiting astrocyte activity effectively reverses behavioral and molecular markers of MOH, highlighting astrocyte inhibition as a promising therapeutic strategy for MOH.

Suzetrigine is a selective voltage-gated sodium channel blocker that was recently approved by the US Food and Drug Administration for the treatment of acute pain. We retrospectively evaluated the efficacy and tolerability of suzetrigine for the treatment of different headache disorders in patients refractory to standard treatments in an academic headache center. These patients had a variety of headache and facial pain diagnoses, including chronic migraine, medication-overuse headache, trigeminal autonomic cephalalgias, nummular headache, occipital neuralgia, and persistent idiopathic facial pain. Some did not clearly meet any diagnostic criteria. The treatment was generally well tolerated, and most patients reported improvement as measured by patient global impression of change. Suzetrigine is a promising new therapeutic approach that warrants further study for the treatment of headache disorders.

BackgroundDespite consistent epidemiological evidence identifying smoking as a risk factor for medication-overuse headache (MOH), the mechanisms underlying this association remain incompletely elucidated. The aim of this work was to explore the relationship between the severity of analgesic dependence, headache-related disability, nicotine dependence, psychological distress, and addiction-related personality traits in patients with MOH.MethodsThis multicenter cross-sectional study was conducted on 442 patients with primary headache disorders. Participants underwent structured face-to-face interviews and were asked to fill out the following questionnaires: Headache Impact Test-6 (HIT-6), Severity of Dependence Scale (SDS), Depression Anxiety Stress Scales-12 (DASS-12), and Substance Use Risk Profile Scale (SURPS). Smoking status was documented for all participants. Current smokers were asked to complete Fagerström Test for Nicotine Dependence questionnaire (FTND).ResultsThis study included 442 patients with primary headache disorders, of whom 150 had MOH and 292 did not. Patients with MOH (n = 150) reported significantly higher monthly headache days (MHD), acute medication days (AMD), HIT-6, DASS-12, and SURPS scores than those without MOH (n = 292) (all P-values < 0.001). Smoking prevalence and FTND scores were significantly higher among MOH patients than those without MOH (all P-values < 0.001). Smokers demonstrated higher MHD, AMD, prevalence of MOH, DASS-12, and SURPS scores than non-smokers (all P-values < 0.05). Among smokers, FTND correlated positively with MHD, AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.001). In patients with MOH, SDS scores showed positive correlations with AMD, HIT-6, DASS-12, and SURPS (all P-values < 0.05).ConclusionSeverity of dependence on analgesics in patients with MOH is strongly associated with headache burden, nicotine dependence, psychological distress, and addiction-related personality traits.

BackgroundOur recent estimate of the global 1-year prevalence of headache among those aged 18–65 years was 65%: considerably higher than previous estimates, but based solely on high-quality epidemiological data derived from a large population-based sample. Here we present complementary estimates of 1-day prevalence.MethodsWe performed a meta-analysis of individual participant data from cross-sectional surveys among population-representative samples (age range 18–65 years) from 15 countries and all world regions. All used the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, including the question “did you have a headache yesterday?”, from which 1-day prevalence was determined. An algorithmic process applying modified ICHD criteria yielded separate estimates for migraine, tension-type headache (TTH) and probable medication-overuse headache (pMOH: the association of headache on ≥ 15 days/month and medication overuse). We analysed associations with age, gender and country-income level, and adjusted prevalence estimates for these factors. We calculated predicted 1-day prevalence from 1-year prevalence and reported headache frequency.ResultsAmong the 38,512 participants, females (53.4%) and participants from low- (17.1%) or lower-middle-income countries (64.6%) were overrepresented, but age distribution fairly matched that of the world. Overall, 13.7% (95% CI: 13.3–14.0) reported headache yesterday, females (17.1% [16.6–17.6]) more than males (9.7% [9.3–10.2]). Migraine was the most common headache type yesterday (6.0% [5.8–6.3]), followed by TTH (4.1% [3.9–4.3]) and pMOH (2.3% [2.2–2.5]). One-day headache prevalence was higher in low/lower-middle-income countries (13.9% [13.6–14.3]) than in high/upper-middle-income countries (12.4% [11.6–13.2]). Predicted 1-day prevalence (10.9% [10.7–11.1]) was considerably lower than observed 1-day prevalence (13.7% [13.3–14.0]), although not among those with pMOH (3.1% [3.0-3.3] versus 2.3% [2.2–2.5]). Adjusted for age, gender and country-income level, global 1-day prevalence estimates were 13.1% (12.8–13.5) for any headache, 5.7% (5.5–5.9) for migraine, 3.9% (3.7–4.1) for TTH and 2.4% (2.3–2.6) for pMOH, with 1.0% undiagnosed.ConclusionAssuming yesterday was no different from any other day, an estimated 13.1% (N = 641,900,000) of the world’s population aged 18–65 years will have headache tomorrow; almost half will be migraine. People with migraine or TTH underestimate the frequency of headache episodes. Since headache-attributed burden is usually estimated from recalled frequency over 1–12 months, this also may be underestimated.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-026-02359-2.

Migraine is a chronic neurological disorder and a leading cause of disability worldwide. In India, it poses a significant public health challenge, with prevalence estimates ranging from 14% to 28.7%. The objective of the work was to assess the epidemiological burden of migraine in India and critically examine clinical, social, and infrastructural challenges impacting its management and policy support. A narrative review of peer-reviewed literature published between 2015 and 2025 was conducted using PubMed, Scopus, and Web of Science, focusing on migraine diagnosis, treatment advances, and policy frameworks. Searches included terms such as "early diagnosis," "medication overuse headache," "policy support," and "novel migraine therapies," prioritizing systematic reviews and meta-analyses. Expert insights were also incorporated through thematic analysis of discussions from a dedicated migraine session at the 69 th Annual National Conference of the Indian Public Health Association (March 2025, Belagavi). The results demonstrate that migraine affects over 213 million individuals in India, disproportionately impacting women and working-age populations. Current therapeutic approaches lack personalization, and access to innovative treatments remains limited due to regulatory and insurance gaps. Policy neglect and sociocultural stigma exacerbate disease burden. This report highlights the debilitating nature of Migraine and the associated economic loss in India, which remains under-recognized in policy and insurance frameworks. A multidisciplinary, patient-centered approach integrating clinical innovation, policy reform, and mental health support is found to be the need of the hour.

Medication overuse headache (MOH) is a chronic disorder due to excessive acute headache treatment use. Neuroimaging studies suggest the involvement of the orbitofrontal cortex (OFC) in the pathophysiology of MOH, particularly its connections with the periaqueductal gray (PAG). The OFC-vlPAG circuit has been well-established as a critical neural substrate in pain regulation; while its role in triptan-related MOH pathogenesis remains unclear. This study aims to investigate the role of the OFC-vlPAG circuit and its underlying mechanisms in regulating mechanical hypersensitivity using a triptan-induced MOH mouse model. Male C57BL/6J mice (along with a female exploratory cohort) were used to develop a triptan-induced MOH model through repeated rizatriptan (RIZ) administration. Behavioral assessments of cutaneous allodynia were conducted using von Frey filaments. Immunofluorescence staining was performed to examine neuronal activity and 5-HT1D receptor (5-HT1DR) expression in the OFC. Chemogenetic and optogenetic techniques were employed to modulate vlOFC glutamatergic neurons or the vlOFC-vlPAG pathway, and pharmacological methods were utilized to target the vlOFC's 5-HT1DR. Repeated RIZ administration induced cutaneous allodynia in the MOH mouse model, with significant reductions in hind paw and head withdrawal thresholds. Elevated c-Fos expression in the vlOFC CaMKII-α+ neurons of triptan-induced MOH mice indicated increased glutamatergic neuronal activity. Chemogenetic and optogenetic glutamatergic neuron activation in the vlOFC alleviates allodynia in the triptan-induced MOH model. Furthermore, glutamatergic vlOFC-vlPAG circuit activation significantly improved pain thresholds in these MOH mice. The observed downregulation of 5-HT1DR in the vlOFC of these MOH mice was functionally associated with inhibition relief in this circuit. This adaptation may create a permissive state, allowing for robust analgesic effects upon targeted exogenous activation. Activating the glutamatergic OFC-vlPAG circuit elicits robust analgesia in triptan-induced MOH mice. 5-HT1DR downregulation is hypothesized to unmask the circuit's analgesic potential by elevating vlOFC baseline activity, providing a highly responsive therapeutic target for triptan-related allodynia. Not applicable.

AimThe phase 4 RESOLUTION trial showed that, in comparison with placebo, adding eptinezumab-an anti-calcitonin gene-related peptide monoclonal antibody-to a brief educational intervention (BEI) reduced the monthly frequency of migraine, headache, and acute medication use in participants with chronic migraine (CM) and medication-overuse headache (MOH). Herein, we report data from multiple patient-reported outcomes (PROs) evaluating treatment impact on disease burden and health-related productivity and quality of life in the RESOLUTION trial.MethodsRESOLUTION was a multi-national (conducted at 76 sites across 11 countries), double-blind, randomized, placebo-controlled trial. The trial comprised a 4-week screening period; a 12-week, double-blind, placebo-controlled period; a 12-week, open-label, extension period; and an 8-week, safety follow-up period, with results of the placebo-controlled period presented in this paper. Adults diagnosed with CM and MOH received a BEI and were randomized 1:1 to intravenous infusion with either eptinezumab 100 mg or placebo. Several PROs were assessed at baseline, Week 4, and Week 12, including the six-item Headache Impact Test (HIT-6), modified Migraine Disability Assessment (mMIDAS), Migraine-specific Work Productivity and Activity Impairment questionnaire (WPAI:M), Patient Global Impression of Change (PGIC; assessed only at follow-up), patient-identified most bothersome symptom (PI-MBS; assessed only at follow-up), Migraine-Specific Quality-of-Life questionnaire version 2.1 (MSQ v2.1), EQ-5D-5L visual analogue scale, and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9; assessed only at follow-up). Post hoc analyses included responder rates for HIT-6 (i.e., participants with ≥5-point reduction from baseline), as well as for PGIC and PI-MBS (i.e., participants who reported "much improved" or "very much improved").ResultsOf 608 participants randomized, the full-analysis set included 302 participants in the eptinezumab arm and 300 in the placebo arm. Eptinezumab with BEI was associated with more favorable PRO scores compared to placebo with BEI, starting at Week 4 (p < 0.05 for all comparisons) and up to Week 12 (p < 0.01 for all comparisons except WPAI:M absenteeism). Responder rates for HIT-6, PGIC, and PI-MBS also favored eptinezumab versus placebo.ConclusionsIn participants with CM and MOH who also received patient education, eptinezumab treatment resulted in greater reductions in headache impact and migraine disability than placebo, with greater improvements in productivity, quality of life, overall disease status, and treatment satisfaction starting from Week 4 and sustained to Week 12. Eptinezumab in combination with patient education is an effective treatment for reducing disease burden and improving overall quality of life in people with CM and MOH.Trial registrationClinicalTrials.gov Identifier: NCT05452239 (https://clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40).

Integrated management of refractory medication-overuse headache in an elderly patient: the clinical efficacy of the Kampo medicine Goshuyuto.

Medication-overuse headache (MOH) is a frequent, disabling, and largely preventable secondary headache disorder, most associated with pre-existing migraine. Since many patients rely on over-the-counter medications and experience long delays before specialist referral, community pharmacists represent key frontline professionals in the identification, counseling, and prevention of medication overuse and MOH. However, data on pharmacists' knowledge and practices regarding migraine and MOH in Italy are still lacking. We conducted a nationwide, cross-sectional survey among Italian pharmacists and pharmacy students using a structured, self-administered questionnaire. The survey assessed demographic characteristics, knowledge of migraine and MOH, dispensing and counseling practices, screening for medication overuse, and referral behaviors. A composite scoring system, the Migraine and Medication Overuse Headache Knowledge and Awareness Scale (MMKAS; range 0-23), was developed by expert consensus to evaluate knowledge and professional behavior. Group comparisons were conducted using independent t-tests or Mann-Whitney U tests and categorical variables were analyzed using chi-square tests with standardized residual post-hoc analysis. For comparisons across more than two groups, one-way ANOVA or Kruskal-Wallis tests were applied, followed by adjusted post-hoc tests. A multivariable linear regression model was performed to identify independent predictors of total MMKAS scores. Internal consistency was evaluated using Cronbach's α coefficient. A total of 271 participants were included (mean age 40.8 ± 11.4 years; 15.5% men), representing all Italian regions. Overall migraine knowledge was generally preserved, whereas awareness of MOH thresholds, preventive strategies, and systematic screening was heterogeneous. Education level was significantly associated with MMKAS performance, while years of professional experience were not. In multivariable analysis, older age and practicing in southern regions were independently associated with higher MMKAS scores. Familiarity with newer preventive therapies, including anti-CGRP pathway drugs, was limited. Italian pharmacists show good general knowledge of migraine but relevant gaps in MOH prevention, systematic screening, and preventive management particularly related to novel anti-CGRP therapeutics. Targeted educational interventions, particularly during undergraduate and early postgraduate training, may strengthen pharmacists' contribution to migraine care and MOH prevention.

Medication Overuse Headache in Children and Adolescents: A Narrative Review.

Migraine ranks second among all conditions in terms of its impact on quality of life and work capacity, and is the leading cause of disability among people under the age of 50. Triptans, which have long been the mainstay of acute treatment, have a number of limitations: contraindications in cardiovascular disease, the risk of developing medication overuse headache (MOH) with frequent use, as well as ineffectiveness or intolerance in a significant proportion of patients. The advent of gepants – antagonists of the calcitonin gene-related peptide (CGRP) receptor - has opened up new possibilities for the treatment of migraine. Rimegepant (Nurtec©) is the first representative of this class to be registered in the Russian Federation and the only drug in the world with two indications: acute attack relief and prophylactic treatment of episodic migraine. This review presents current data on the mechanisms of action, efficacy, safety and impact on functional recovery of rimegepant in the acute treatment of migraine. An analysis was conducted of data from clinical trials (randomised controlled trials, open-label long-term trials, and real-world clinical practice studies), systematic reviews and meta-analyses focusing on the use of rimegepant for the relief of migraine attacks. Rimegepant acts via a dual mechanism of antagonism against CGRP receptors and amylin 1 receptors (AMY1), providing effective relief of pain and associated symptoms in a broad population of adult migraine patients. Unlike triptans, the drug does not cause vasoconstriction and has no cardiovascular contraindications. In a 52-week safety study, no cases of MOH were recorded; the frequency of use remained stable with a downward trend. Rimegepant is effective in patients with triptan failure or intolerance (55.9 % vs 32.7 % for placebo; p &lt; 0.0001). The drug provides a rapid onset of action (from 15 minutes), relief of the most debilitating symptom within 2 hours in 40.2 % of patients (compared with 29.2 % in the placebo group; p &lt; 0.0001) and high treatment satisfaction (71.4 % vs 52.0 % for triptans; p &lt; 0.001). According to the WPAI-GH questionnaire, rimegepant significantly reduces presenteeism (by 10.6 %; p = 0.018) and overall work impairment (by 11.3 %; p = 0.021), restoring patients' ability to work. The cardiovascular safety of the drug has been confirmed in a population of patients with cardiovascular risk factors (incidence of serious adverse events 2.4 % in the FRS ≥10 % group vs 2.6 % in the low-risk group). Thus, rimegepant is a highly effective and safe agent for the relief of migraine attacks, offering key advantages over triptans: the absence of vaso-constriction and cardiovascular contraindications, minimal risk of developing MOH, efficacy in patients unresponsive to triptans, rapid restoration of work capacity, and high patient satisfaction. The drug may be considered the treatment of choice in these patient populations.

Introduction . The treatment of patients with chronic migraine (CM) and medication overuse headache (MOH) is an actual problem in neurology. Predictors of treatment effectiveness for CM and MOH have been poorly studied. Aim . To study the prognostic factors of therapeutic response in CM. Materials and methods . 54 patients (11 men, 43 women) with CM aged 18 to 50 years (average age 39 years), with or without MOH received preventive treatment for 12 months with evaluation of results every 2 months. Patients kept a headache diary. The questionnaire took place during each visit and included assessments using the VAS (Visual Analog Scale), SF-36 (SF-36 Health Status Survey), MIDAS (Migraine Disability Assessment), MSQ v2.1 (Migraine Specific Quality of Life Questionnaire version 2.1), Morisky – Green Medication Adherence Scale, Sleep Quality Questionnaire, CSI-A (Central Sensitization Inventory), LDQ (Leeds Dependence Questionnaire), HIT-6 (Headache Impact Test-6), HADS (Hospital Anxiety and Depression Scale). Results . The baseline monthly migraine frequency was associated with the MSQ v2.1 (restrictive function: β = -0.17, preventive function: β = -0.14, emotional function: β = -0.06, p &lt; 0.001), SF-36 (PH: β = -0.37, MH: β = -0.02, p &lt; 0.001), LDQ (β = 0.5, p &lt; 0.001), HIT-6 (β = 0.47, p &lt; 0.001), CSI-A (β = 0.19, p &lt; 0.001) scores. The baseline MIDAS score was associated with the results of the LDQ (β = 6.1, р &lt; 0.001), CSI-A (β = 2, р &lt; 0.001), HIT-6 (β = 3.46, р &lt; 0.001), НАDS-A (β = 4.5, р &lt; 0.001), HADS-D (β = 2.82, р = 0.014), SF-36 (PH: β = -3.4, MH: β = -2, р &lt; 0.001), MSQ v2.1 (restrictive function: β = -1.66, preventive function: β = -1.77, emotional function: β = -0.9, p &lt; 0.001) and Sleep Quality Questionnaire (β = -4.5, р &lt; 0.001). However, these factors were not associated with the dynamics of reduction in the frequency of headaches and MIDAS. On the background of preventive therapy headache frequency decreased by 2 episodes per month (β = -2.15, p &lt; 0.001), and the MIDAS score decreased by almost 9 points (β = -8.95, p &lt; 0.001). MOH was not a significant predictor of migraine dynamics (p = 0.072) and severity on the MIDAS scale (p = 0.24). Conclusion . The duration of preventive treatment under the control of a specialist is the main predictor of a positive therapeutic response in CM and MOH.