Cephalalgia最新文献

{"title":"Post-stress modulation of the HPA and melanocortin systems alleviates migraine-like behaviors in mice.","authors":"Ya-Yu Hu, Hao-Ruei Mei, Shruti Sankar, Abbas Pirwani, Armen Akopian, Christa McIntyre, Gregory Dussor","doi":"10.1177/03331024251352856","DOIUrl":"https://doi.org/10.1177/03331024251352856","url":null,"abstract":"<p><p>BackgroundStress is a major trigger for migraine attacks. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, releasing glucocorticoids (GCs) to maintain homeostasis, and migraine attacks may occur as an adverse effect of this response. We previously demonstrated in a mouse model that inhibiting corticosterone (CORT) synthesis by administering metyrapone before stress prevented stress-induced migraine-like behaviors. Given the unpredictable nature of stressors and their onset or termination, it is critical to better understand the adaptive and maladaptive effects of the HPA stress response. Here, we aimed to evaluate the effects of HPA axis modulation following the end of stress exposure.MethodsRepeated stress induces migraine-like behaviors and priming to sodium nitroprusside (SNP) in mice. Metyrapone (to inhibit CORT synthesis), CORT (to evaluate its effects after exogenous administration), and adrenocorticotropic hormone (ACTH) (to test the effects of a hormone upstream to CORT) were administered post-stress. Additionally, α-melanocyte-stimulating hormone (α-MSH, an ACTH cleavage product) and tetrahydroisoquinoline (THIQ), a melanocortin 4 receptor (MC4R) agonist, were administered to examine melanocortin receptor involvement. Facial hypersensitivity was assessed via von Frey testing and grimace scoring was used to evaluate non-evoked pain. Serum CORT levels were measured in both control and stressed mice following ACTH administration.ResultsWe examined post-stress HPA axis modulation on stress-induced facial hypersensitivity. Metyrapone reduced acute-phase hypersensitivity and reduced priming to SNP, suggesting sustained synthesis of CORT after stress plays a role in development of migraine-like behavior. Surprisingly, both CORT and ACTH treatments at 1- and 24-h post-stress alleviated stress-induced behaviors and priming. To determine if ACTH effects were mediated by an elevation in circulating CORT, metyrapone was administered before the ACTH injection. Metyrapone increased the ACTH reversal of stress effects on facial hypersensitivity. Furthermore, post-stress ACTH injections significantly increased serum CORT levels within 30 min. In addition to ACTH effects on CORT levels, ACTH effects could be mediated by the melanocortin system. Post-stress administration of α-MSH or the MC4R agonist THIQ, reduced migraine-like behaviors.ConclusionsThere is a complex relationship between stress, the HPA axis, and melanocortin signaling, in the effects of repeated stress exposure on migraine-like behaviors. In the early post-stress response phase, there are contributions from both CORT and MC4R signaling in the maintenance of behavioral effects. These findings suggest that targeting the HPA axis and MC4R after stress may be a potential therapeutic approach for stress-induced migraine attacks.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251352856"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590575","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 ongoing pursuit of migraine triggering mechanisms.","authors":"Anna P Andreou, Luigi Francesco Iannone","doi":"10.1177/03331024251342583","DOIUrl":"https://doi.org/10.1177/03331024251342583","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251342583"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583226","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":"Childhood traumas delineate a distinct psychological and clinical profile in adults with migraine: The hidden burden.","authors":"Sara Bottiroli, Martina Cangelosi, Marta Allena, Roberto De Icco, Daniele Martinelli, Gloria Vaghi, Elena Guaschino, Natascia Ghiotto, Grazia Sances, Cristina Tassorelli","doi":"10.1177/03331024251358503","DOIUrl":"https://doi.org/10.1177/03331024251358503","url":null,"abstract":"<p><p>ObjectiveThis study aimed to explore how childhood trauma (CT) affects the psychological, clinical and demographic characteristics of migraine patients.MethodsA sample of subjects with chronic migraine with medication overuse (CM + MO) (n = 192) and episodic migraine (EM) (n = 84) was assessed for CT, psychological profiles (via DSM-5-based clinical interviews and self-report questionnaires) and migraine characteristics.ResultsCT was detected in 40% of the total population, being more prevalent in the CM + MO subgroup (41%) versus the EM subgroup (36%) (<i>p</i> = 0.006). The CT group showed a higher prevalence of personality disorders (PDs), particularly Cluster B (12% vs. 4%) and Cluster C (60% vs. 34%), as well as psychopathologies (94% vs. 75%); <i>p</i> = 0.001). The CT group also exhibited greater anxiety, depression, alexithymia and exposure to current stressful life events (<i>p</i> = 0.001). CT participants were more frequently women, had an earlier migraine onset and a higher intake of acute medications. In the multivariate analysis, only Cluster C PDs (i.e., obsessive-compulsive PD), psychopathologies (i.e., anxiety disorders), stressful life events, difficulty identifying feelings (alexithymia), and female sex remained significant.ConclusionsCT is associated with psychological comorbidities, an earlier onset of migraine and a higher intake of acute medications, leading to a more complex migraine phenotype<b>.</b></p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251358503"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752462","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":"Genome sequencing reveals the <i>Adgrl3</i> (<i>ADGRL3</i>) gene as a possible cause of cephalic hypersensitivity in the STA rat and migraine in humans.","authors":"Brian Skriver Nielsen, Hongru Wang, Tanya Ramdal Techlo, Lisette Kogelman, Sarah Louise Christensen, Sanne Hage la Cour, Sabrina Prehn Lauritzen, Gordon Munro, Steffen Petersen, Marlene Danner Dalgaard, Morten Erik Allentoft, Thomas Folkmann Hansen, Rasmus Nielsen, Jes Olesen, Inger Jansen-Olesen, David Møbjerg Kristensen","doi":"10.1177/03331024251352844","DOIUrl":"https://doi.org/10.1177/03331024251352844","url":null,"abstract":"<p><p>BackgroundMigraine is a common primary headache disorder with a significant genetic component influencing its pathophysiology, in which the trigeminal system plays a central role. The spontaneous trigeminal allodynia (STA) inbred rat strain is a validated migraine model that exhibits a chronic cephalic hypersensitive phenotype, responsive to specific migraine treatments. The heritable STA trait presents a unique opportunity to dissect the genetic component of migraine.MethodsSTA rats were backcrossed twice with wild-type (WT) Sprague-Dawley (SD) rats and whole-genome sequencing was performed on 47 rats exhibiting either the STA or WT phenotype. mRNA and protein expression analyses were conducted in the trigeminovascular system of both rats and humans. Based on data from the STA rats, we performed an F-SKAT (i.e. sequence kernel association test for family data) analysis to investigate a potential link between families with clustering of migraine and our findings from the STA rats.ResultsSequencing of STA rats revealed a risk locus near the gene for adhesion G protein-coupled receptor L3 (<i>Adgrl3</i>). In humans, the <i>ADGRL3</i> gene showed an increased burden of rare variants segregating with migraine in families with a clustering of the condition (<i>p</i> = 0.046). We found similar associations between migraine and the <i>ADGRL3</i> when expanding the analyses to a genome-wide analysis including rare variants from more than one million individuals with migraine. Expression analyses of rat and human tissues confirmed that Adgrl3 is expressed in the migraine-associated trigeminovascular system.ConclusionsIn this translational study, <i>ADGRL3</i> was associated with both cephalic hypersensitivity in STA rats and an increased burden of rare variants in humans with migraine. The gene was expressed in the trigeminovascular system, a central pathophysiological component of cephalic pain. <i>ADGRL3</i> provides novel insights into the pathophysiology of chronic cephalic pain in migraine.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251352844"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599541","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":"Genetic characterization of the endocannabinoid system and psychiatric features in patients with migraine and medication overuse headache.","authors":"Marina Romozzi, Lucia Scipioni, Sonia Di Tella, Maria Caterina Silveri, Letizia Maria Cupini, Catello Vollono, Mauro Maccarrone, Paolo Calabresi","doi":"10.1177/03331024251314460","DOIUrl":"https://doi.org/10.1177/03331024251314460","url":null,"abstract":"<p><p>BackgroundThe endocannabinoid system (ECS) is one of the key endogenous systems regulating pain. Preclinical and clinical evidence suggests a dysregulation of the ECS in patients with migraine. The present study aimed to characterize the main ECS components in patients with chronic migraine and medication overuse headache (MOH) and episodic migraine (EM) at the gene expression level compared to healthy controls (HC) and to correlate the findings with psychopathological scales.MethodsIn this cross-sectional study, consecutive patients with a diagnosis of EM and MOH were enrolled. Fatty acid amide hydrolase (FAAH) was assayed through quantitative enzyme-linked immunosorbent assay kits. The gene expression of ECS components (FAAH, <i>N</i>-arachidonoyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and <i>N</i>-acylethanolamine acid amidase (NAAA) enzymes, cannabinoid (CB) receptors, CB₁ and CB₂, transient receptor potential vanilloid type 1 (TRPV1) and peroxisome proliferator-activated receptor (PPAR)ɑ receptors was assayed in peripheral blood mononuclear cells through a real-time quantitative PCR. Clinical data including Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) were collected. Psychopathological status was assessed through the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Rating Scale for Depression (HAM-D) and the Toronto Alexithymia Scale (TAS-20).ResultsThe study included 31 patients (15 with EM, 16 with MOH) and 14 HC. The gene expression of FAAH, an enzyme involved in the degradation of the main endocannabinoid, was significantly lower in MOH patients (0.0002 ± 0.0002) than in EM patients (0.0008 ± 0.0006) (<i>p</i> = 0.005). There were no significant differences in gene expression among EM, MOH and HC groups for NAPE-PLD, NAAA, CB₁, CB₂, TRPV1 and PPARɑ. The levels of FAAH protein expression were significantly higher in MOH (2.9517 ± 2.2006 pg/μg) compared to EM patients (0.9225 ± 0.6878 pg/μg) (<i>p</i> = 0.025). In the clinical group (EM and MOH), we found a significant negative correlation between FAAH gene expression and FAAH enzyme protein (<i>p</i> = 0.014); FAAH gene expression negatively correlated with HIT-6 (<i>p</i> = 0.003) and MIDAS scores (<i>p</i> = 0.048), as well with all psychopathological scales, in more detail with TAS-20 (<i>p</i> = 0.029), HAM-A (<i>p</i> = 0.040) and HAM-D (<i>p</i> = 0.028).ConclusionsFAAH undergoes specific alterations in patients with MOH at gene expression levels, suggesting its potential as a blood biomarker for this condition. FAAH gene expression is possibly related to psychiatric comorbidities in migraine patients.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251314460"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539184","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 comparison of the persistence of acute treatment with rimegepant versus oral triptans in patients with migraine: A retrospective analysis of US claims data.","authors":"Stewart J Tepper, Aaron Jenkins, Carl Henriksen, Feng Dai, Jo Atkinson, Lucy Abraham, Astrid Gendolla","doi":"10.1177/03331024251352849","DOIUrl":"10.1177/03331024251352849","url":null,"abstract":"<p><p>BackgroundThis study compared persistence of patients initiating rimegepant versus oral triptans for the acute treatment of migraine.MethodsA retrospective cohort analysis was conducted using US MarketScan claims data (1 March 2019 to 30 June 2023) among commercially- and US federal Medicare-insured migraine patients initiating rimegepant or oral triptans. Persistence was defined as having ≥1 refill within 12 months of initial prescription and was compared between propensity score-matched rimegepant and triptan cohorts.ResultsBefore matching, 13,599 patients were identified in the rimegepant cohort and 38,127 in the triptan cohort. After matching, each cohort included 9909 patients. Significantly more rimegepant patients were persistent (75.8%) versus triptan patients (53.5%) (odds ratio [OR] 2.72, 95% confidence interval [CI] 2.56-2.90). Subgroup analyses showed similar trends for rimegepant versus specific triptans (rizatriptan: OR 2.49 [95% CI 2.33-2.67], and sumatriptan: OR 2.92 [95% CI 2.73-3.12]) and in patients with chronic migraine (OR 2.86 [95% CI 2.53-3.23]).ConclusionsThis study provides compelling evidence that rimegepant is associated with greater persistence than oral triptans for real-world acute treatment of migraine. Rimegepant is a favorable option for patients seeking effective and tolerable long-term treatment, particularly for those with insufficient response, intolerability, or contraindications to triptans.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251352849"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728286","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":"Interactive CBT for headache and relaxation training (iCHART): Single-arm pilot trial of cognitive behavioral therapy for veterans with post-traumatic headache.","authors":"Amy S Grinberg, Daniel G Rogers, Olivia Datre, Sarah Anthony, Sarah W Clark, Stanley C Takagishi, Elizabeth Seng, Brenda T Fenton, John P Ney, Jason J Sico","doi":"10.1177/03331024251351598","DOIUrl":"10.1177/03331024251351598","url":null,"abstract":"<p><p>BackgroundCognitive behavioral therapy for headache (CBT-HA) improves headache-related outcomes, but accessibility barriers limit its use. This pilot study evaluated the feasibility, acceptability and clinical signal of an interactive voice response (IVR)-delivered CBT-HA intervention for veterans with post-traumatic headache (PTH).MethodsA single-arm pilot trial was conducted with 18 veterans diagnosed with PTH. Participants completed a 10-week IVR-CBT-HA program. Outcomes were assessed at baseline, immediately post-treatment and one-month follow-up. Primary outcomes included changes in headache days, interference, disability, feasibility and acceptability.ResultsFifteen participants completed the study. Headache frequency, headache-related disability, depressive symptoms, anxious symptoms, sleep quality and headache catastrophizing were not statistically significant. Self-efficacy significantly improved from baseline to post-treatment (<i>F</i>_2,12 = 8.71, <i>p</i> = 0.001), and remained stable at follow-up. Participants reported high satisfaction with the intervention (27.73/32, SD = 5.66) but low system usability (mean = 20.83/100, SD = 15.72). Study therapists rated the intervention as highly acceptable (acceptability of intervention: mean = 4.83/5, SD = 0.37) and feasible (feasibility of intervention measure: mean = 4.92/5, SD = 0.28). Interactive CBT for headache and relaxation training (i.e. iCHART) resulted in an approximately 33% cost savings compared to traditional CBT-HA.ConclusionsAsynchronous, IVR-delivered CBT-HA was feasible, acceptable and cost-effective for veterans with PTH. Although headache reductions were not statistically significant, self-efficacy improvements suggest long-term benefits. Future research should explore technology refinements and larger randomized trials.Trial RegistrationClinicalTrials.gov: NCT05093556 (registered 26 October 2021).</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251351598"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625493","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":"An analysis of diffusion tensor imaging in classical trigeminal neuralgia.","authors":"Margaret Tugend, Colby T Joncas, Katie Traylor, Marion A Hughes, Raymond F Sekula","doi":"10.1177/03331024251322505","DOIUrl":"https://doi.org/10.1177/03331024251322505","url":null,"abstract":"<p><p>BackgroundDiffusion tensor imaging (DTI) may demonstrate microstructural changes in diseased trigeminal nerves. Few prognostic indicators for long-term pain freedom after microvascular decompression (MVD) of the trigeminal nerve have been identified. The present study aimed to determine whether microstructural changes from DTI are present in the trigeminal nerve of patients with classical trigeminal neuralgia (cTN) due to arterial compression or deformation and whether they may be used to predict surgical success.MethodsPatients with a diagnosis of cTN due to arterial compression or deformation that underwent MVD from October 2013 until December 2020, with high resolution 3T magnetic resonance imaging DTI, and over two years of post-surgical follow-up were included in this study. The microstructural metrics of the symptomatic and asymptomatic trigeminal nerve were compared using a paired, two-sided Student's <i>t</i>-test. Differences between the microstructural metrics of the symptomatic nerve between treatment responders and treatment non-responders were assessed using Welch's <i>t</i>-test due to unequal variances and/or unequal sample sizes.ResultsEighty-eight patients met inclusion criteria and were analyzed. There was no significant difference in fractional anisotropy (FA) (<i>p</i> = 0.3658), mean diffusivity (MD) (<i>p</i> = 0.1734) and radial diffusivity (RD) (<i>p</i> = 0.6586) between the symptomatic and asymptomatic nerve. There was a significant difference in AD (<i>p</i> = 0.0186). However, after the sequential modified Bonferroni correction, the difference in AD no longer reached significance. There was no significant difference in FA (<i>p</i> = 0.7556), MD (<i>p</i> = 0.8915), RD (<i>p</i> = 0.4324) and AD (<i>p</i> = 0.9918) in the symptomatic nerve between the treatment responders and non-responders.ConclusionsDTI may not reliably predict outcomes of microvascular decompression in patients with cTN due to arterial compression or deformation.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251322505"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752461","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":"Comment on comment on \"Toward ICHD-4: Proposing a broader diagnostic framework for burning mouth syndrome\".","authors":"Gilad Wasserman, Iftah Biran, Ayelet Zlotogorski Hurvitz","doi":"10.1177/03331024251362822","DOIUrl":"https://doi.org/10.1177/03331024251362822","url":null,"abstract":"","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251362822"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728288","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 randomized open-label study to evaluate the effectiveness and safety of once-daily rimegepant 75 mg orally disintegrating tablet for the short-term preventive treatment of fasting-triggered headache in individuals with migraine.","authors":"Taoufik Alsaadi, Reem Suliman, Jiyue Yang, Ekta Agarwal, Terence Fullerton, Denise E Chou, Ed Whalen, Caline El Jadam, Ibrahim Al Qaisi, Youssef Amin, Athra Alkhateri, Kareem Alsaffarini, Lucy Abraham, Zahra Zunaed, Haytham M Ahmed, Mohamed Fathy, Mohamed Hegab, Nora Vainstein","doi":"10.1177/03331024251355947","DOIUrl":"10.1177/03331024251355947","url":null,"abstract":"<p><p>AimTo evaluate rimegepant, a calcitonin gene-related peptide receptor antagonist, for short-term prevention of fasting-triggered headache during Ramadan.MethodsParticipants, aged 18-65 years and diagnosed with migraine or headache attributed to fasting, were randomized to open-label once-daily (QD) rimegepant 75 mg orally disintegrating tablet (ODT) from weeks 1-4 of the fast (Immediate Start arm; n = 52) or weeks 2-4 of the fast (Staggered Start arm; n = 53). The primary endpoint was the difference in number of headache days of any intensity between the Immediate Start and Staggered Start arms during week 1. Other endpoints included headache days during weeks 2-4, moderate-to-severe headache days during weeks 1-4, headache duration (any intensity and moderate-to-severe) during weeks 1-4, rescue medication use during weeks 1-4 and treatment satisfaction. Treatment comparisons utilized nominal <i>p</i> values. Safety endpoints included adverse events (AEs), serious AEs and discontinuations due to AEs.ResultsAll participants (n = 105) had a diagnosis of migraine and a history of headaches during fasting. The number of headache days of any intensity during week 1 (primary endpoint) was lower in the Immediate Start arm vs. the Staggered Start arm (LS mean (95% confidence interval) = 1.74 (1.16-2.31) days vs. 2.92 (2.34-3.49) days; <i>p</i> = 0.005). There were no significant differences between arms during weeks 2-4. Total duration of headaches of any intensity was shorter in the Immediate Start arm vs. the Staggered Start arm during week 1 (LS mean (95% confidence interval) = 10.1 (5.9-17.5) hours vs. 20.0 (13.0-28.3) hours; <i>p</i> = 0.041) and week 4 (LS mean (95% confidence interval) = 0.9 (0.2-3.7) hours vs. 4.6 (2.2-15.5) hours; <i>p</i> = 0.035). The number and duration of moderate-to-severe headaches was significantly (<i>p</i> < 0.05) lower in the Immediate Start arm vs. the Staggered Start arm during week 1. For the overall 4-week study period, there was a significant reduction in moderate-to-severe headache days per week in the Immediate Start arm vs. the Staggered Start arm (LS mean (95% confidence interval) = 0.60 (0.34-0.86) days vs. 1.00 (0.75-1.26) days; <i>p</i> = 0.038) and a trend towards reduction in headache days per week of any severity (LS mean (95% confidence interval) = 1.05 (0.72-1.39) days vs. 1.50 (1.17-1.84) days; <i>p</i> = 0.070). Use of rescue medication trended lower in the Immediate Start arm vs. the Staggered Start arm at all study weeks; all <i>p</i> > 0.05. Most participants (82.4%) reported being satisfied, very satisfied, or extremely satisfied with rimegepant at end of treatment. No AEs were reported.ConclusionsQD rimegepant 75 mg ODT may be effective and well tolerated for short-term prevention of fasting-triggered headache in individuals with migraine.</p>","PeriodicalId":10075,"journal":{"name":"Cephalalgia","volume":"45 7","pages":"3331024251355947"},"PeriodicalIF":4.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741348","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}