Headache最新文献

{"title":"A machine learning-driven transcriptomic study reveals the key role of Romo1 in reversing central sensitization through stellate ganglion block in migraine: An interventional study based on a recurrent migraine rat model.","authors":"Fei Yang, Xiaomao Tian, Yao Xu, Shun Yang, Shengfen Tu, Li Jiang","doi":"10.1111/head.14997","DOIUrl":"https://doi.org/10.1111/head.14997","url":null,"abstract":"<p><strong>Objectives/background: </strong>This study utilized a nitroglycerin (NTG)-induced chronic migraine rat model to explore the therapeutic effects and underlying mechanisms of stellate ganglion block (SGB), aiming to clarify the potential pathogenesis of migraine. Central sensitization is key to chronic migraine development. SGB effectively treats chronic pain by reducing sympathetic tone and inhibiting central sensitization. Although SGB is a promising treatment for migraine based on several observational studies, its mechanisms of action remain partially understood.</p><p><strong>Methods: </strong>Migraine was experimentally induced in rats by administering repeated injections of NTG. Ultrasound-guided SGB was used as the intervention. Hyperalgesia was evaluated through measurements of paw mechanical hyperalgesia, periorbital mechanical threshold, and paw withdrawal latency. The impact of SGB on migraine was assessed by measuring c-fos and calcitonin gene-related peptide (CGRP) levels in the trigeminal nucleus caudalis using Western blotting and immunohistochemistry. Differentially expressed downstream genes were identified through bulk transcriptome sequencing, potential biological mechanisms were explored using gene ontology enrichment analysis, and phenotype characteristic genes were identified through various machine learning algorithms. The expression of key genes was validated using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry.</p><p><strong>Results: </strong>Repeated NTG treatment increased c-fos and CGRP expression, along with chronic mechanical and thermal hypersensitivity. SGB treatment alleviated hyperalgesic symptoms and decreased CGRP and c-fos levels in the trigeminal nucleus caudalis. Machine learning analysis revealed a significant increase in Romo1 (reactive oxygen species modulator 1) expression in the migraine model, which notably decreased after SGB treatment. Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry confirmed Romo1's significant role in migraine pathophysiology.</p><p><strong>Conclusion: </strong>SGB mitigates central sensitization and reduces migrainelike symptoms in a rat model of migraine induced by repeated NTG exposure. Our results suggest that Romo1 is associated with the effects of SGB, and based on our statistical analysis, is an interesting target for future studies.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the alterations in microstate dynamics during the migraine cycle and detecting pre-ictal phases.","authors":"Siyuan Xie, Yunyun Huo, Xinyi Geng, Li Hu, Ran Ao, Hui Su, Desheng Li, Miaomiao Hu, Yusha Liu, Xiaomei Chen, Jinghuan Liu, Qianqian Li, Jiayin Lin, Shengyuan Yu, Zhao Dong","doi":"10.1111/head.15031","DOIUrl":"https://doi.org/10.1111/head.15031","url":null,"abstract":"<p><strong>Background: </strong>Microstate analysis captures brief but critical fluctuations in brain activity, making it a powerful tool for exploring the cyclic nature of migraine. In this study, we aimed to investigate microstate features during different migraine phases and develop a classification model to identify the pre-ictal phase.</p><p><strong>Methods: </strong>From May 2023 to June 2024, we conducted a cross-sectional study with consecutive recruitment, collecting resting-state electroencephalography data from 174 individuals with migraine without aura and 50 healthy controls, followed by classification of migraine phases. Microstate features, Lempel-Ziv complexity, and sample entropy were compared across five groups. A model was developed to identify the pre-ictal phase and validated on a test set.</p><p><strong>Results: </strong>Microstate features, particularly for microstates A and B, exhibited dynamic changes across the migraine cycle. The duration of microstate A was significantly longer in the inter-ictal phase than in the pre-ictal phase, whereas microstate B showed prolonged duration in the pre-ictal phase compared to healthy controls and the post-ictal phase. Microstate A displayed reduced coverage in the pre-ictal phase, whereas microstate B had increased occurrence and coverage during the pre-ictal and ictal phases. Transition probabilities also varied significantly: the pre-ictal phase showed elevated transitions from microstates A, C, and D to B, and the post-ictal phase showed reduced transitions from C and D to A. A classification model based on these microstate features achieved an area under the receiver operating characteristic curve (AUROC) of 0.85 (0.73-0.95), an area under the precision-recall curve (AUPRC) of 0.83 (0.66-0.95), and an F1 score of 0.78 (0.62-0.90) in the training set; and an AUROC of 0.84 (0.69-0.97), an AUPRC of 0.86 (0.67-0.98), and an F1 score of 0.81 (0.65-0.93) in the test set, indicating robust performance in identifying the pre-ictal phase.</p><p><strong>Conclusion: </strong>Through the observation of cyclic alterations in the microstates of patients with migraine, we identified a reduction in microstate A and an enhancement in microstate B during the pre-ictal phase. These changes may indicate a heightened sensitivity to auditory stimuli and increased activity in the visual cortex, providing new insights into migraine pathophysiology. Our model effectively identified the pre-ictal phase, offering a promising approach for early intervention in migraine attacks.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The state of insurance coverage of calcitonin gene-related peptide-targeted medications and its impact on the implementation of the American Headache Society's 2024 consensus statement: An interrupted time-series analysis.","authors":"Leon S Moskatel, David J G Slusky","doi":"10.1111/head.15027","DOIUrl":"https://doi.org/10.1111/head.15027","url":null,"abstract":"<p><strong>Objective: </strong>To determine if insurers updated formularies and step therapy requirements after the American Headache Society's (AHS) March 2024 consensus statement for the prevention of migraine that changed calcitonin gene-related peptide (CGRP)-targeted medications to first-line treatments, and if there was an associated expansion in patients prescribed these medications.</p><p><strong>Background: </strong>Insurance company formularies and step therapy requirements should ideally mirror the recommendations provided by the AHS. The AHS' March 2024 consensus statement for medications for the prevention of migraine made CGRP-targeted medications first-line treatments, removing the recommendation for first pursuing two 8-week trials of non-specific oral medications.</p><p><strong>Methods: </strong>We conducted a retrospective study using the Epic Cosmos electronic health record database, insurance formulary, and step therapy information. The Epic Cosmos research platform was queried for patients with migraine and prescriptions for the CGRP-targeted medications by month from May 1, 2023, to January 31, 2025. Our primary outcomes were the time-trend in the prescription of the CGRP-targeted therapies during the study interval and whether there was an immediate increase in patients using CGRP-targeted medications or change in the rate of utilization after the March 2024 AHS consensus statement. Secondary outcomes included this analysis for patients with chronic migraine, based on care setting, and with the post-release period broken into early and late phases. Insurance formularies and step therapy requirements were reviewed for coverage of the CGRP-targeted medications.</p><p><strong>Results: </strong>Our study included 6,898,995 patients with migraine and 929,793 patients with chronic migraine. During the study period, prescriptions for all CGRP-targeted preventive medications by all providers showed statistically significant increases, excluding erenumab, which was unchanged. For none of the queried CGRP-targeted medications in the main analysis, was the AHS consensus statement's release linked to an increase in their usage. Conversely, for patients with chronic migraine, in the non-neurology setting, a small immediate increase was seen for fremanezumab, erenumab, and atogepant, but this was offset by a subsequent slowing of the overall rate of increase in their utilization in this setting (-0.07 percentage point change in rate of uptake for any CGRP-targeted medication by month; 95% confidence interval, -0.10 to -0.04, p < 0.001). Although insurance coverage for at least one of the CGRP-targeted medications was high (142 of 149 plans, 95.3%), individual medication coverage varied with 126 of 149 (84.6%) of plans covering galcanezumab but only 93 of 149 (62.4%) covering atogepant. Step therapy requirements including trials of non-specific oral medications before starting CGRP-targeted therapies were largely in place 10 months after ","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galcanezumab reduces trigeminal nociception and is effective in preclinical models of migraine and trigeminal autonomic cephalalgias.","authors":"Marta Vila-Pueyo, Peter J Goadsby, Kirk W Johnson, Philip R Holland","doi":"10.1111/head.15006","DOIUrl":"https://doi.org/10.1111/head.15006","url":null,"abstract":"<p><strong>Objectives/background: </strong>This study was undertaken to assess the therapeutic efficacy of galcanezumab in preclinical models of migraine and cluster headache and to determine potential shared trigeminovascular mechanisms of action. Galcanezumab is a humanized monoclonal antibody that binds to the neuropeptide calcitonin gene-related peptide, preventing its biological activity. It has been approved as a preventive treatment for both episodic and chronic migraine and episodic cluster headache, the most common trigeminal autonomic cephalalgia.</p><p><strong>Methods: </strong>Trigeminovascular and trigeminal-autonomic reflex activation was evoked via electrical stimulation of the dura mater or superior salivatory nucleus (SSN), respectively. Evoked responses were recorded in the spinal trigeminal nucleus along with ongoing spontaneous neuronal and cutaneous noxious-evoked and non-noxious-evoked neuronal activity. Rats received either galcanezumab or human control IgG, and responses were compared between groups.</p><p><strong>Results: </strong>Galcanezumab robustly reduced spontaneous (maximum decrease in dural-evoked: 73% [±3.5] at 4 h 30 min [p = 0.002]; in SSN-evoked: 67% [±10.7] at 4 h [p = 0.01]) and cutaneous non-noxious-evoked (maximum decrease in dural-evoked: 50% [±5.7], p = 0.004; in SSN-evoked: 47% [±10.5], p = 0.005, at the last recording time point) neuronal activation in the trigeminocervical complex, highlighting a general inhibition of trigeminal sensory processing. Furthermore, it significantly inhibited cutaneous noxious-evoked (maximum decrease in dural-evoked: 38% [±5.2], p = 0.005; in SSN-evoked: 34% [±7.6], p = 0.005, at the last recording time point), durovascular-evoked (maximum decrease 48% [±6] at the last recording time point, p = 0.001), and SSN-evoked responses (maximum decrease: 32% [±2.6] at 4 h, p < 0.001), demonstrating a clear reduction of trigeminal nociception, independent of the mode of activation. Galcanezumab did not have any effect on the mean arterial blood pressure.</p><p><strong>Conclusion: </strong>Galcanezumab likely acts via a shared trigeminovascular mechanism to dampen noxious and nonnoxious sensory stimuli in preclinical models of migraine and trigeminal autonomic cephalalgias. This further supports the clinical efficacy of galcanezumab for migraine and cluster headache, while demonstrating general inhibition that may be of relevance to other facial pain conditions.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in brainstem habituation during onabotulinumtoxinA treatment in chronic migraine: A prospective case-control study.","authors":"Gerlinde Freimark, Sebastian Strauss, Lucas H Overeem, Mira P Fitzek, Kristin S Lange, Carolin L Höhne, Uwe Reuter, Robert Fleischmann, Bianca Raffaelli","doi":"10.1111/head.15021","DOIUrl":"https://doi.org/10.1111/head.15021","url":null,"abstract":"<p><strong>Objectives/background: </strong>Chronic migraine is a debilitating neurological disorder characterized by central sensitization and impaired brainstem habituation. OnabotulinumtoxinA is an established prophylactic treatment for chronic migraine, yet its effects on central trigeminal sensory processing remain incompletely understood. The nociceptive blink reflex (nBR) is a well-established neurophysiological tool for assessing brainstem excitability and central sensory processing within the trigeminal system. This prospective case-control study investigated longitudinal changes in brainstem neurophysiology following onabotulinumtoxinA treatment using the nBR.</p><p><strong>Methods: </strong>Between November 2022 and April 2024, we assessed nBR habituation in 27 patients with chronic migraine and compared them with 27 age- and sex-matched healthy controls. Measurements were performed at peak efficacy (1 month postinjection, Month 1+) and prior to reinjection (3 months postinjection, Month 3+). Habituation of the polysynaptic R2 response was analyzed as the primary outcome.</p><p><strong>Results: </strong>At Month 1+, R2 nBR habituation in patients was similar to that observed in healthy controls (4-s interstimulus interval, ipsilateral: β = 0.10, 95% confidence interval [CI] = -0.16 to 0.36, p = 0.457); however, by Month 3+, patients showed a significant impairment in R2 habituation compared to healthy controls (4-s interstimulus interval, ipsilateral: β = -0.29, 95% CI = -0.55 to -0.03, p = 0.029). Correlation analyses revealed that reduced habituation was associated with increased monthly migraine days (4-s interstimulus interval, contralateral: r = 0.41, 95% CI = 0.02 to 0.69, p = 0.039) and prolonged intervals since the last onabotulinumtoxinA treatment (4-s interstimulus interval, Month 3+, ipsilateral: r = 0.33, 95% CI = 0.06 to 0.55, p = 0.018), which aligns with the clinical observation of wearing off. Supporting this notion, patients with more prior treatment cycles exhibited sustained improvement in habituation deficits (4-s interstimulus interval, Month 3+, ipsilateral: r = -0.46, 95% CI = -0.71 to -0.09, p = 0.017). The monosynaptic R1 component remained unchanged between Month 1+ and 3+ (4-s interstimulus interval, ipsilateral: β = -0.028, 95% CI = -0.067 to 0.011, p = 0.164), emphasizing a specific treatment effect of trigeminal system-mediated pain processing at the brainstem level.</p><p><strong>Conclusion: </strong>These findings indicate that onabotulinumtoxinA exerts a neuromodulatory effect on brainstem neurophysiology, with R2 habituation improving during peak treatment efficacy and declining as the effect wears off. The results underscore the time-dependent central effects of onabotulinumtoxinA on nociceptive processing within the trigeminal system. Future research should investigate the nBR as a potential biomarker for optimizing onabotulinumtoxinA treatment strategies in chronic migraine.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing triptan safety in emergency settings under cardiovascular risk uncertainty.","authors":"Yalcin Golcuk","doi":"10.1111/head.15020","DOIUrl":"https://doi.org/10.1111/head.15020","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of opioid and barbiturate use following initiation of rimegepant for migraine in the United States.","authors":"Noah Rosen, Aaron Jenkins, Karin Hygge Blakeman, Feng Dai, Lucy Abraham, Chelsea Leroue, Josh Brown","doi":"10.1111/head.15004","DOIUrl":"https://doi.org/10.1111/head.15004","url":null,"abstract":"<p><strong>Objective: </strong>The primary objective of this study was to evaluate opioid and barbiturate utilization before and after the first prescription of the calcitonin gene-related peptide receptor antagonist rimegepant in individuals with migraine.</p><p><strong>Background: </strong>Although not recommended in migraine treatment guidelines, opioids and barbiturates are often prescribed for the acute treatment of migraine, despite the risks of dependence and harm. Initiating a migraine-specific acute treatment might reduce the use of opioids and barbiturates.</p><p><strong>Methods: </strong>This retrospective cohort study among adults in the United States with migraine and a first prescription for rimegepant (fill quantity of eight tablets, indicative of acute treatment) was based on administrative claims data from the IQVIA PharMetrics Plus longitudinal health plan database (September 1, 2019, through March 31, 2023). For opioids and butalbital (separately), number of prescription fills and average dispensed amounts (as morphine milligram equivalents [MME] and milligrams [mg], respectively) were assessed in the 180 days preceding (pre-index) and the 180 days following (post-index) rimegepant initiation. Subgroup analyses included individuals using ≥ 1 preventive treatment, and individuals with problematic opioid use (≥ 3 opioid prescriptions and/or MME in the fourth quartile).</p><p><strong>Results: </strong>Among 1928 opioid users, rimegepant initiation was associated with a significant difference in opioid prescription fills (median [interquartile range (IQR)] 2 [1-5] pre-index vs. 1 [0-5] post-index, p < 0.001) and average dispensed MME (25 [17.5-37.5] pre-index vs. 14 [0-30] post-index, p < 0.001), and 740 users (38.4%) discontinued opioids. Among 873 butalbital users, rimegepant initiation was associated with a significant difference in butalbital prescription fills (median [IQR] 2 [1-4] pre-index vs. 1 [0-3] post-index, p < 0.001) and average dispensed mg (200 [100-300] pre-index vs. 25 [0-187.5] post-index, p < 0.001), and 422 users (48.3%) discontinued opioids. Rimegepant initiation was associated with reduction of opioid and butalbital utilization in the subgroups using preventive treatment, and reduction of opioid utilization in the subgroup with problematic opioid use.</p><p><strong>Conclusions: </strong>Rimegepant initiation was associated with reductions in utilization of opioids and butalbital, including in individuals using preventive treatment for migraine, and with reduction of opioid utilization in individuals with problematic opioid use.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective cohort study to evaluate the effectiveness and safety profile of occipital nerve blocks in the treatment of migraine during pregnancy.","authors":"Liza Smirnoff, Leon Moskatel, Blake Shaw, Zihuai He, Addie Peretz","doi":"10.1111/head.15001","DOIUrl":"https://doi.org/10.1111/head.15001","url":null,"abstract":"<p><strong>Objectives/background: </strong>Nearly 12% of Americans experience migraine, with 75% of that group represented by women aged 15-55 years, notably including peak childbearing years. This presents a therapeutic dilemma for pregnant patients, given that most medications for migraine range from unknown teratogenicity in human pregnancies, at best, to known teratogenicity, severely limiting their utility. However, migraine causes significant disability and impairment in the lives of pregnant patients, necessitating treatment. We conducted a retrospective chart review and phone survey to evaluate the safety profile and effectiveness of bilateral occipital nerve blocks to treat migraine during pregnancy.</p><p><strong>Methods: </strong>We conducted a retrospective review of charts of women aged 18-50 years who received bilateral occipital nerve blocks at the Stanford Headache Clinic between January 1, 2014 and December 31, 2020 during their pregnancies for the treatment of migraine and followed up with phone call surveys to address fetal outcomes as well as effectiveness of the nerve blocks.</p><p><strong>Results: </strong>Thirty patients met inclusion criteria, and 21 responded to our survey. Of the 21 surveyed, none experienced significant pregnancy complications, negative fetal outcomes, or an increased rate of miscarriage. Participants receiving nerve blocks noted a reduction in pain on a visual analog scale from an average of 7 to 2 (p < 0.001) as well as from 9 days to 4 days of acute medication use per month (p = 0.002).</p><p><strong>Conclusion: </strong>Based on this limited retrospective cohort study, serial occipital nerve blocks may offer a safe and potentially effective option for treatment of migraine during pregnancy. Occipital nerve blocks may improve the overall quality of life, decrease disability rates, and decrease the use of potentially teratogenic therapies in pregnant women. Future larger and prospective studies are needed to better assess the safety profile and effectiveness of occipital nerve blocks for pregnant patients with migraine.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milk and plasma pharmacokinetics of single-dose ubrogepant in healthy lactating women.","authors":"Ramesh R Boinpally, Jonathan H Smith, Eric Cohen, Joel M Trugman","doi":"10.1111/head.14960","DOIUrl":"10.1111/head.14960","url":null,"abstract":"<p><strong>Objective: </strong>The objectives of this study were to evaluate the safety, plasma and milk pharmacokinetics, excretion in breast milk, and the relative infant dose of ubrogepant following a single oral dose.</p><p><strong>Background: </strong>Ubrogepant is a calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine in adults. Preclinical findings in rats demonstrated comparable concentrations of ubrogepant in milk versus plasma; however, the quantification of ubrogepant excretion in human breast milk and breastfed infant exposure have not been previously evaluated.</p><p><strong>Methods: </strong>This open-label, phase 1 study (NCT05892757) enrolled healthy, lactating adult women from July 11, 2023, to February 22, 2024. Participants were 1-6 months postpartum and received a single dose of ubrogepant 100 mg (2 × 50 mg tablets) orally. Plasma and breast milk samples were collected for up to 24 h after dosing to evaluate pharmacokinetics and ubrogepant concentrations were determined using validated liquid chromatography tandem mass spectrometry assays. Standard pharmacokinetic parameters were calculated from the plasma concentration and breast milk data using non-compartmental analyses. The milk-to-plasma concentration ratio was calculated based on the ratio of the area under the plasma concentration-time curve from time 0 to infinity (AUC_∞) of human milk to the AUC_∞ of plasma. The relative infant dose was calculated as 100 times the quotient of the body weight-normalized infant dose and the body weight-normalized maternal dose. Safety and tolerability were assessed via adverse events, vital signs, electrocardiograms, and clinical laboratory measurements.</p><p><strong>Results: </strong>A total of 12 women were enrolled who each received a single dose of oral ubrogepant 100 mg. The mean milk-to-plasma ratio was 0.23, the cumulative amount of ubrogepant excreted in breast milk was <0.02% and the calculated relative infant dose was 0.15%. The maximum observed breast milk concentration and AUC of ubrogepant in breast milk were significantly lower (75% and 78%, respectively) compared to plasma. Only two mild adverse events were reported.</p><p><strong>Conclusion: </strong>Less than 0.02 mg of a 100 mg dose of ubrogepant was excreted in breast milk over a 24-h period. The minimal transfer of ubrogepant into breast milk is not considered clinically relevant.</p>","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1190-1197"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracranial hypertension with papilledema associated with long-term use of over-the-counter retinol day cream.","authors":"Matthieu Batens, Liesbeth Huys, Sven Dekeyzer, Nicolas Vandenbussche, Elke O Kreps","doi":"10.1111/head.14978","DOIUrl":"10.1111/head.14978","url":null,"abstract":"","PeriodicalId":12844,"journal":{"name":"Headache","volume":" ","pages":"1207-1208"},"PeriodicalIF":5.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}