Effectiveness of Rimegepant in Vestibular Migraine: A Prospective Self-controlled Cohort Study

Effectiveness of Rimegepant in Vestibular Migraine: A Prospective Self-controlled Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effectiveness of Rimegepant in Vestibular Migraine: A Prospective Self-controlled Cohort Study Jinyan Shao, Jingxin Fu, Mengting Zhou, Zewei Ren, Longxiang Li, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8009385/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Dec, 2025 Read the published version in The Journal of Headache and Pain → Version 1 posted 9 You are reading this latest preprint version Abstract Background Vestibular migraine (VM) is the second most common cause of episodic vertigo worldwide, yet effective therapeutic options remain limited. This study aimed to assess the clinical effectiveness of rimegepant in patients with VM. Methods A total of 33 VM cases were enrolled in this multicenter, prospective self-controlled cohort study, screened from an initial pool of 106 patients. Mean 4-week days of vestibular symptom or headache, along with Dizziness Handicap Inventory (DHI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Headache Impact Test-6 (HIT-6), Vertigo Symptom Scale–Short Form (VSS-SF), Activities-specific Balance Confidence Scale (ABC) scores, and hearing sensitivities were compared between pre-dosing and postdosing of rimegepant over a 4-week follow-up. Results At baseline, participants exhibited a high symptom burden, with elevated DHI, VSS-SF, GAD-7, PHQ-9, and HIT-6 scores and low ABC scores. After rimegepant treatment, there were substantial reductions in monthly vestibular symptom days and headache days (differences: vestibular symptoms, -8.48; headache, -5.88). Totally 63.6% and 70.4% of the patients experienced a 50% reduction in vestibular symptom days and headache days, respectively. Notably, these improvements were already apparent at 2 weeks, indicating early onset of efficacy. Additionally, rimegepant treatment led to significant improvements in vestibular function (differences: DHI, -27.33; VSS-SF, -6.21), psychological status (differences: GAD-7, -3.33; PHQ-9, -3.33), and quality of life (differences: HIT-6, -11.27; ABC, 19.98). Pure tone audiometry (PTA) results also indicated improvements in hearing. Conclusions Rimegepant provides relief of vestibular symptoms and improves psychological well-being and hearing in patients with VM, with efficacy evident as early as 2 weeks. Trial registration: NCT04939922 Vestibular migraine Rimegepant Real-world Treatment Figures Figure 1 Figure 2 Figure 3 Background Vestibular migraine (VM) is a syndrome characterized by recurrent episodes of vestibular symptoms. Globally, VM is the second most common cause of episodic vertigo [ 1 ]. According to the latest guidelines [ 2 ], the diagnosis of VM is based on four criteria: (1) at least five attacks of moderate or severe vestibular symptoms, defined by the Bárány Society [ 3 ]; (2) a history of migraine per the International Classification of Headache Disorders, third edition (ICHD-3); (3) at least half of the attacks accompanied by one of the following symptoms: headache, photophobia, phonophobia, or visual aura; and (4) symptoms that cannot be better explained by other ICHD-3 diagnoses or other vestibular disorders. VM’s lifetime prevalence is 1% in Germany [ 4 ], versus 2.7% in the United States [ 5 ]. Notably, VM cases account for up to 30% of patients seeking treatment for episodic dizziness [ 6 ]. In China, a study reported that 9.2% patients with dizziness or vertigo were diagnosed with VM, accounting for 54.1% of patients with central vestibular disorders (CVD) [ 7 ]. Despite the large number of VM patients, there is a lack of effective therapeutic drugs. Some studies suggest that VM patients may benefit from migraine treatments, including acute medications (such as gepants [ 8 ], triptans [ 9 ], and vestibular inhibitor [ 10 ]) and preventive treatments (e.g., calcitonin gene-related peptide (CGRP) medications [ 11 ], β-blockers [ 12 ], and calcium channel blockers [ 13 ]). Currently, VM treatment relies primarily on traditional medications, which often have poor efficacy, delayed onset (4–6 weeks), and considerable adverse effects (AEs) [ 14 ]. Meanwhile, evidence supporting the efficacy of these traditional medications for VM is limited. In 2023, Cochrane Reviews concluded that there is insufficient evidence to support the use of acute-care or prophylactic medications for VM [ 15 ], with only one placebo-controlled randomized clinical trial (RCT) on prophylaxis included [ 16 ]. Other studies have shown that triptans are ineffective in VM treatment and do not improve vertigo attacks [ 15 , 17 ]. In contrast, Russo et al. recently reported that CGRP monoclonal antibodies (mAbs) may improve both vertigo and headache in a prospective observational cohort study [ 18 ]. Anti-CGRP drugs, including gepants and mAbs, offer promising potential for overcoming the current treatment impasse. In preclinical studies, gepants have shown encouraging effects in motion sickness therapy. For example, olcegepant significantly alleviated nausea in mouse models of migraine induced by CGRP and sodium nitroprusside (SNP) [ 19 ] and improved vestibular function through the PKC/ERK/CREB pathway in a rat model of chronic migraine [ 20 ]. Hoskin et al. reported a retrospective clinical analysis of anti-CGRP agents for VM, and while the study size was small (only two patients treated with ubrogepant), the findings suggested that anti-CGRP drugs could be a potential treatment option for VM [ 21 ]. Additionally, anti-CGRP drugs have demonstrated potential preventive benefits in RCTs [ 22 ]. Rimegepant, a first-generation anti-CGRP agent, showed significant therapeutic efficacy in acute migraine attacks in a multicenter, randomized, controlled, double-blind clinical trial [ 23 ]. However, its efficacy in alleviating vestibular symptoms in VM remains unclear. Therefore, the aim of our study was to assess the effectiveness of rimegepant in VM patients. Methods Study design and participants This prospective multicenter cohort study aimed to assess the real-world effectiveness of rimegepant in VM. The study was conducted at Sir Run Run Shaw Hospital and the Second Affiliated Hospital, Zhejiang University School of Medicine, with approval from the institutional ethics committee. All participants provided written informed consent prior to any study-related procedures. Inclusion criteria were: diagnosis consistent with the Bárány Society criteria for VM or probable VM (pVM) [ 2 ], age ≥ 18 years, no prior use of anti-CGRP drugs. Exclusion criteria included other potential vestibular diseases, incomplete questionnaires or follow-up, pregnancy or lactation in women, unwillingness to fille e-diaries or questionnaires, and serious medical or psychiatric conditions. Two attending physicians confirmed the diagnosis. Ultimately, 33 participants were included. Study outcomes The clinical characteristics, demographics, and medical histories of all participants were recorded. A total of 33 patients were included in the analysis out of 106 VM or pVM cases. At baseline, all 33 patients completed the following assessments: Dizziness Handicap Inventory (DHI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Headache Impact Test-6 (HIT-6), Vertigo Symptom Scale–Short Form (VSS-SF), and Activities-specific Balance Confidence Scale (ABC). Patients were followed up for 4 weeks, during which they were administered rimegepant at 75 mg every other day. Follow-up visits occurred every two weeks. At each visit, the numbers of vestibular symptom days and headache days, and medications taken during the preceding 14 days were recorded. The week-2 visit may be conducted by telephone, the week-4 visit must be face-to-face, and all the scales listed above were re-administered at Week 4. The definition of vestibular symptoms referred to the criteria of the Bárány Society [ 2 ]. Hearing assessments were performed before and after treatment, and complete air and bone conduction values were recorded for 22 patients. Adverse events (AEs) related to rimegepant were also recorded for safety assessment. The primary outcome was reduction in mean number of vestibular symptom days over 4 weeks postdosing. Secondary outcomes included mean number of headache days over 4 weeks postdosing, mean number of vestibular symptom days every 2 weeks, mean number of headache days every 2 weeks, and changes in assessment scale scores related to vertigo, dizziness, mood, anxiety, and hearing. Statistical analysis All data were recorded in Microsoft Excel (version 16.7). Baseline variables were summarized using descriptive analysis. Categorical variables were expressed as frequency and percentage, and continuous variables as mean ± standard deviation (SD). The McNemar’s test was applied for categorical data. Normality was assessed by normality and log-normality tests. For non-normally distributed data, the Wilcoxon Mann–Whitney U test was applied; otherwise, two-way paired or unpaired t-test was used. The Wilcoxon signed-rank test was performed for data with unequal variance. Cohen’s d was used to calculate effect sizes. For comparisons involving multiple variables, one-way ANOVA was conducted. Statistical analyses were conducted with SPSS (version 22.0, IBM), and data visualization was performed with GraphPad Prism (version 9.5.1). A two-tailed P value < 0.05 was considered statistically significant. Results Participant screening and clinical features in the VM cohort A total of 106 patients with VM or pVM were initially considered for inclusion in the current study. Of these, 55 were enrolled, while 16 patients declined follow-up, 11 used other anti-CGRP drugs, and 24 continued alternative therapies. During the follow-up period, 1 patient was excluded due to the influence of other comorbidities, 11 due to improper medication use, 4 due to loss to follow-up, and 6 for unknown reasons. Ultimately, 33 patients were included in the analysis (Fig. 1 ). The 33 enrolled participants had a mean age of 45.19 years, with 78.8% being female (Table 1 ). Before treatment, the monthly frequencies of vestibular symptoms and headache were 16.36 ± 9.29 and 10.55 ± 9.10, respectively. In addition, mean DHI and VSS-SF scores were 47.58 ± 25.67 and 14.64 ± 10.12, respectively. Mean GAD-7 and PHQ-9 scores were 6.64 ± 5.67 and 7.48 ± 5.61, respectively, while HIT-6 and ABC scores were 61.27 ± 8.19 and 67.42 ± 30.76, respectively. These findings indicated that VM patients with vestibular dysfunction and headache experienced substantial psychological distress and impairment in daily life. Table 1 Baseline characteristics Variable N = 33 Age 45.19 ± 15.04 Gender Male 7 (21.2%) Female 26 (78.8%) DHI 47.58 ± 25.67 DHI-P 13.82 ± 8.62 DHI-E 14.61 ± 9.61 DHI-F 19.15 ± 10.08 DHI-Mild 8 (24.2%) DHI-Moderate 13 (39.4%) DHI-Severe 12 (36.4%) GAD-7 6.64 ± 5.67 PHQ-9 7.48 ± 5.61 HIT-6 61.27 ± 8.19 VSS-SF 14.64 ± 10.12 VSS-SF_F 12.15 ± 8.70 VSS-SF_E 2.48 ± 2.06 ABC 67.42 ± 30.76 Vestibular symptoms (days per month) 16.36 ± 9.29 Headache (days per month) 10.55 ± 9.10 DHI, Dizziness Handicap Inventory; DHI-P, DHI- Physical; DHI-E, DHI-Emotional; DHI-F, DHI- Functional; GAD-7, Generalized Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9; HIT-6, Headache Impact Test-6; VSS-SF, Vertigo Symptom Scale–Short Form; VSS-SF_F, VSS-Functional; VSS-SF_E, VSS-Emotional; ABC, Activities-specific Balance Confidence Scale. Rimegepant provides short-term relief of vestibular symptoms and headache in VM To investigate the early onset of efficacy, the 2-week frequencies of vestibular symptoms and headache were assessed (Fig. 2 ). During the rimegepant treatment period, both mean vestibular symptom and headache days showed significant decreases at 2 weeks (vestibular symptoms: 5.68 ± 4.38 vs. 8.18 ± 4.65, P = 0.0391; headache: 2.95 ± 3.91 vs. 5.27 ± 4.55, P = 0.0318) and at 4 weeks (vestibular symptoms: 3.21 ± 3.77 vs. 8.18 ± 4.65, P < 0.0001; headache: 2.06 ± 2.89 vs. 5.27 ± 4.55, P = 0.0020). Rimegepant demonstrates improvements in vestibular and psychological outcomes and hearing after 4 weeks After 4 weeks of rimegepant treatment, VM patients showed relief of vestibular symptoms and improvement in psychological well-being (Table 2 ). The monthly frequencies of vestibular symptoms (7.88 ± 8.01) and headache (4.67 ± 5.19) decreased significantly, with large effect sizes (vestibular symptoms: P = 0.0002, Cohen’s d = 0.98; headache: P = 0.0062, Cohen’s d = 0.79). Of these patients, 63.6% and 70.4% experienced a 50% reduction in vestibular symptoms and headache, respectively. Furthermore, DHI scores (20.24 ± 24.53), including the physical (6.42 ± 6.78), emotional (5.76 ± 8.35), and functional (8.06 ± 10.52) subdomains, were significantly improved compared with baseline, with large effect sizes ( P 0.8). VSS-SF scores (8.42 ± 9.01), comprising the functional (dizziness and balance disorders) (7.00 ± 7.28) and emotional (autonomic symptoms) (1.42 ± 1.95) domains, also showed a significant improvement with moderate effect sizes ( P 0.5). Similarly, GAD-7 (3.30 ± 4.63) and PHQ-9 (4.15 ± 4.49) scores demonstrated significant reductions, indicating improved psychological status ( P 0.5). In addition, both HIT-6 (50.00 ± 10.26) and ABC (87.41 ± 16.09) scores improved significantly after treatment ( P < 0.05). Table 2 Outcomes after a 4-week rimegepant treatment Variable Baseline 4 weeks Difference a P- value Effect size DHI 47.58 ± 25.67 20.24 ± 24.53 -27.33 (-36.54, -18.12) < 0.0001 1.09 DHI-P 13.82 ± 8.62 6.42 ± 6.78 -7.39 (-10.24, -4.55) 0.0002 0.95 DHI-E 14.61 ± 9.61 5.76 ± 8.35 -8.85 ( -12.02, -5.68 ) < 0.0001 0.98 DHI-F 19.15 ± 10.08 8.06 ± 10.52 -11.09 (-15.23, -6.96) < 0.0001 1.08 GAD-7 6.64 ± 5.67 3.3 ± 4.63 -3.33 (-5.08, -1.59) 0.0086 0.65 PHQ-9 7.48 ± 5.61 4.15 ± 4.49 -3.33 (-5.21, -1.46) 0.0071 0.66 HIT-6 61.27 ± 8.19 50.00 ± 10.26 -11.27 (-15.20, -7.35) < 0.0001 1.21 VSS-SF 14.64 ± 10.12 8.42 ± 9.01 -6.21 (-10.24, -2.19) 0.0069 0.65 VSS-SF_F 12.15 ± 8.70 7.00 ± 7.28 -5.15 (-8.45, -1.86) 0.0085 0.64 VSS-SF_E 2.48 ± 2.06 1.42 ± 1.95 -1.06 (-1.98, -0.14) 0.0158 0.53 ABC 67.42 ± 30.76 87.41 ± 16.09 19.98 (9.96, 30.01) 0.0050 -0.81 Vestibular symptoms (days per month) 16.36 ± 9.29 7.88 ± 8.01 -8.48 (-10.92, -6.05) 0.0002 0.98 Headache (days per month) 10.55 ± 9.10 4.67 ± 5.19 -5.88 (-8.40, -3.35) 0.0062 0.79 DHI, Dizziness Handicap Inventory; DHI-P, DHI- Physical; DHI-E, DHI-Emotional; DHI-F, DHI- Functional; GAD-7, Generalized Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9; HIT-6, Headache Impact Test-6; VSS-SF, Vertigo Symptom Scale–Short Form; VSS-SF_F, VSS-Functional; VSS-SF_E, VSS-Emotional; ABC, Activities-specific Balance Confidence Scale. a Difference expressed as mean value and 95% confidence interval (CI). Moreover, hearing assessments of air and bone conduction were performed for 22 patients using PTA (Fig. 3 ). In the left ear, 12 patients showed reduced air conduction and 7 displayed reduced bone conduction. In the right ear, 16 patients had decreased air conduction and 15 had reduced bone conduction. Notably, air conduction in the right ear showed a significant improvement ( P = 0.0148). Collectively, these findings suggest that rimegepant provides relief of vestibular symptoms and improves psychological state in patients with VM, with an early onset of efficacy observed at 2 weeks. Discussion In this cohort study, rimegepant was effective in patients with VM by improving both vestibular symptoms and psychological well-being. This is the first cohort study to evaluate rimegepant for VM treatment in China. Currently, commonly recommended drugs for VM prevention primarily aim to relieve symptoms or improve the quality of life. These mainly include tricyclic antidepressants (e.g., nortriptyline [ 24 ] and venlafaxine [ 25 ]), β-blockers (e.g., propranolol [ 26 ]), and antiepileptic drugs (topiramate and valproic acid [ 27 ]), which are known to improve vertigo and headache in VM. Bayer et al. investigated the effects of metoprolol succinate (a β-blocker) over 6 months in VM patients, reporting a reduction of 1.4 days in monthly vertigo attacks [ 16 ]. Liu et al. assessed three drugs (venlafaxine, flunarizine, and valproic acid), reporting reductions of 2.74 days (venlafaxine), 0.8 days (flunarizine), and 2.75 days (valproic acid) in vertigo attacks after 3 months of treatment [ 28 ]. In this study, rimegepant reduced monthly vertigo days by 8.48 after only one month of use, suggesting it may offer superior therapeutic effects with a fast onset. In a small study of rimegepant in patients with concurrent vestibular migraine (VM) and Ménière’s disease (MD), all five participants administered rimegepant 48-hourly as preventive therapy experienced complete resolution of vertigo during the 8-month treatment period, suggesting favorable efficacy [ 29 ]. Another small head-to-head trial confirmed a good efficacy and safety profile for galcanezumab in VM [ 22 ]. These findings are consistent with our results, suggesting that CGRP-targeted therapies may be highly effective for vestibular migraine. As for therapeutic efficacy, since these traditional migraine preventive medications are not specifically designed for VM, their therapeutic efficacy remains controversial. For example, a meta-analysis of 828 VM patients demonstrated significant benefits for valproic acid, propranolol, and venlafaxine [ 30 ]. In contrast, other studies have reported the poor effects and tolerability of these agents in VM [ 31 ]. Furthermore, adverse events (AEs) associated with these drugs are common and, in some cases, serious. Nortriptyline may cause dry mouth, constipation, orthostatic hypotension, and/or confusion. Venlafaxine can lead to elevated blood pressure and worsened headache. Propranolol should be used cautiously in patients with angiocardiopathy or asthma due to its β-blocker effects. Common side effects of topiramate include cognitive impairment, sensory disturbances, and mood disorders, while valproic acid is often associated with weight gain or tremors. In this study, no patient reported any moderate or severe drug-related adverse events, and there was no treatment discontinuation due to side effects; in addition, all adverse reactions were mild and required no additional intervention. Nonetheless, there is an urgent need for more effective and better-tolerated therapies for VM. Our findings support the effectiveness of rimegepant and provide valuable clinical evidence for its use in VM. In this study, rimegepant demonstrated effectiveness in improving both vestibular symptoms and headache at an early time. Significant improvements with large effect sizes were detected in clinical assessments, including DHI and VSS-SF scores. The DHI evaluates the quality of life in VM patients across three domains: functional, emotional, and physical [ 32 ]. The VSS-SF assesses the severity and frequency of vestibular symptoms [ 33 ]. These improvements reflect meaningful symptom relief. Notably, other studies have also reported that different medications can reduce DHI scores. For example, Görür et al. found that botulinum toxin, propranolol, amitriptyline, and flunarizine reduced DHI scores [ 34 ]. However, their effects took up to three months, whereas rimegepant in this study showed significant reductions after only one month of treatment. Additionally, the VSS-SF showed excellent improvements. While the focus is often on VM symptoms, psychological distress should also be considered. It was reported that up to 50% of patients with vertigo symptoms have psychological disorders [ 35 ]. In this study, the GAD-7 and PHQ-9 scales were used to assess anxiety and depression in VM patients. The GAD-7 scale is primarily used to screen for and assess the severity of anxiety disorders [ 36 ], while the PHQ-9 scale is used to screen for and assess the severity of depressive symptoms [ 37 ]. The rapid relief of vestibular symptoms in this study was associated with improvements in anxiety and depression. For quality of life assessments, the HIT-6 and ABC scales were used. The HIT-6 scale evaluates the disease burden and the quality of life [ 38 ], while the ABC scale assesses the confidence in maintaining balance during daily activities [ 39 ]. Improvements in both vestibular symptoms and psychological status contributed to the observed improvements in the quality of life. While reductions were also observed in VSS-SF, GAD-7, and PHQ-9 scores, the effect sizes were moderate. We speculate that this may be because approximately half of the examined patients had long-standing, severe anxiety and significant impairment in daily life, suggesting that a longer treatment course might be required for individuals with severe psychological comorbidities. Additionally, the predominance of middle-aged female patients (mean age: 42.3 years) raises the possibility that hormonal fluctuations may have affected treatment outcomes [ 40 ]. Furthermore, hearing assessments through PTA testing were conducted. In over half of the assessed patients, hearing test values were reduced in both ears. While the improvements were modest, air conduction in the right ear showed a significant improvement. This suggests that rimegepant may exert an effect on hearing, potentially explained by the distribution of CGRP in the inner ear. It has been reported that CGRP and its receptors are expressed at moderate-to-high levels in the central nervous system and inner ear [ 41 , 42 ]. Additionally, Rahman et al. reported that CGRP can alter auditory function, with these effects reversed by CGRP antagonists [ 19 , 43 , 44 ]. In contrast, CGRP mAbs currently require injection [ 21 ], making oral administration of rimegepant a more convenient option. However, a significant improvement was observed in this study only in right-ear air-conduction thresholds, with no significant benefit detected in left-ear air conduction or bilateral bone conduction. We speculate that audiological improvement may require a prolonged treatment, and studies with extended therapy and follow-up are therefore warranted. This study had several limitations. First, it had a single-arm design in which efficacy was assessed through self-comparison before and after treatment. Future trials should include placebo-controlled groups to strengthen validity. Second, the sample size was relatively small, and all participants were Chinese. Studies with larger cohorts including different races and regions are warranted to better generalize the therapeutic effects of rimegepant. Third, this analysis used a short treatment period of 4 weeks, with preventive effects evaluated as early as 2 weeks; further research is needed to assess the efficacy of rimegepant in relieving acute symptoms and long-term preventive efficacy. Finally, this investigation focused on a single CGRP antagonist. Comparative studies including traditional agents (e.g., SSRIs, valproic acid, propranolol) and anti-CGRP mAbs are required to fully delineate relative efficacy and safety profiles. Conclusions In conclusion, rimegepant provides meaningful relief of vestibular symptoms and improves psychological well-being in patients with VM, with clinical benefits evident as early as 2 weeks. These findings support the potential of rimegepant as a valuable therapeutic option for VM. Abbreviations VM Vestibular migraine DHI Dizziness Handicap Inventory GAD-7 Generalized Anxiety Disorder-7 PHQ-9 Patient Health Questionnaire-9 HIT-6 Headache Impact Test-6 VSS-SF Vertigo Symptom Scale–Short Form ABC Activities-specific Balance Confidence Scale ICHD-3 International Classification of Headache Disorders PTA Pure tone audiometry CVD Central vestibular disorders CGRP Calcitonin gene-related peptide RCT Randomized clinical trial mAbs Monoclonal antibodies SNP Sodium nitroprusside AEs Adverse events pVM Probable VM SD Standard deviation CI Confidence interval SSRIs Serotonin reuptake inhibitors TVS Trigeminovascular system VG Vestibular ganglia CSD Cortical spreading depression Declarations Acknowledgements We thank all the medical staff who assisted in the outpatient work and are grateful to Dr. Chen Guoqiao for guidance regarding the article. Author contributions SJY and LKM: Conceptualization, Formal analysis and Methodology. FJX and ZMT: Writing - Original Draft. RZW, LLX, GLL, XYH, ZZX, YMN and HJH: Investigation, Resources, Data Curation. SJY, FJX and ZMT contributed equally to this work. All authors contributed to the final manuscript. All authors read and approved the final manuscript. Funding This study was supported by the Key Research and Development Program of Zhejiang Province (Grant No. 2024C03007). Data availability Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact. Ethics approval and consent to participate All participants provided written informed consent prior to enrollment. They were notified that deidentified study-related data would be used in compliance with local regulations on privacy and data protection. 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BMC Ear Nose Throat Disord 8:2 Görür K, Gür H, İsmi O, et al (2022) The effectiveness of propranolol, flunarizine, amitriptyline and botulinum toxin in vestibular migraine complaints and prophylaxis: a non-randomized controlled study . Braz J Otorhinolaryngol 88:975-981 Lahmann C, Henningsen P, Brandt T, et al (2015) Psychiatric comorbidity and psychosocial impairment among patients with vertigo and dizziness . J Neurol Neurosurg Psychiatry 86:302-308 Spitzer RL, Kroenke K, Williams JB, et al (2006) A brief measure for assessing generalized anxiety disorder: the GAD-7 . Arch Intern Med 166:1092-1097 Kroenke K, Spitzer RL, and Williams JB (2001) The PHQ-9: validity of a brief depression severity measure . J Gen Intern Med 16:606-613 Kosinski M, Bayliss MS, Bjorner JB, et al (2003) A six-item short-form survey for measuring headache impact: the HIT-6 . Qual Life Res 12:963-974 Powell LE and Myers AM (1995) The Activities-specific Balance Confidence (ABC) Scale . J Gerontol A Biol Sci Med Sci 50a:M28-34 Sierra I, Pyfrom S, Weiner A, et al (2023) Unusual X chromosome inactivation maintenance in female alveolar type 2 cells is correlated with increased numbers of X-linked escape genes and sex-biased gene expression . Stem Cell Reports 18:489-502 Dudek A, Sienkiewicz W, and Kaleczyc J (2012) Immunohistochemical characterization of neurons in the vestibular ganglion (Scarpa's ganglion) of the pig . Pol J Vet Sci 15:499-507 Holland PR, Saengjaroentham C, and Vila-Pueyo M (2019) The role of the brainstem in migraine: Potential brainstem effects of CGRP and CGRP receptor activation in animal models . Cephalalgia 39:390-402 Rahman SM, Hauser C, Faucher S, et al (2024) A Vestibular Challenge Combined with Calcitonin Gene-Related Peptide (CGRP) Promotes Anxiety-Like Behaviors . eNeuro 11 Rahman SM, Faucher S, Jonnala R, et al (2025) Systemic calcitonin gene-related peptide modifies auditory and vestibular end organ electrical potentials, and increases sensory hypersensitivities . J Neurophysiol 134:107-117 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Dec, 2025 Read the published version in The Journal of Headache and Pain → Version 1 posted Editorial decision: Revision requested 18 Nov, 2025 Reviews received at journal 15 Nov, 2025 Reviews received at journal 14 Nov, 2025 Reviewers agreed at journal 07 Nov, 2025 Reviewers agreed at journal 05 Nov, 2025 Reviewers invited by journal 05 Nov, 2025 Editor assigned by journal 04 Nov, 2025 Submission checks completed at journal 04 Nov, 2025 First submitted to journal 02 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8009385","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":541771248,"identity":"cf082e3a-28c4-4f62-98c7-7f271b7918f8","order_by":0,"name":"Jinyan Shao","email":"","orcid":"","institution":"Sir Run Run Shaw Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jinyan","middleName":"","lastName":"Shao","suffix":""},{"id":541771249,"identity":"f55839bc-9bb5-4075-8f02-c8a41d5366d3","order_by":1,"name":"Jingxin Fu","email":"","orcid":"","institution":"Second Affiliated Hospital of Zhejiang 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07:19:38","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":103984,"visible":true,"origin":"","legend":"","description":"","filename":"df0d713cb7ae401eb4d3ebbcd277bdde1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8009385/v1/e4fe23256c4295dee1a708b3.xml"},{"id":95940030,"identity":"95bf1ae0-402a-4c74-926d-63cfc5f52b18","added_by":"auto","created_at":"2025-11-14 16:08:35","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":115047,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8009385/v1/a46590e5ea9755288f883c2b.html"},{"id":95940032,"identity":"6d457ed1-0d8f-41c7-849a-ecb49057a74a","added_by":"auto","created_at":"2025-11-14 16:08:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":204985,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy flowchart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8009385/v1/6014767be7b0d9e0289b8dd7.png"},{"id":95940031,"identity":"50da8646-c35f-4eb5-96e1-f42036469141","added_by":"auto","created_at":"2025-11-14 16:08:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":192792,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMean days with vestibular symptoms and headache at 2 weeks and 4 weeks.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA-B. \u003c/strong\u003eVestibular symptoms.\u003cstrong\u003e C-D. \u003c/strong\u003eHeadache. Values are mean ± standard deviation (SD).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8009385/v1/7243c12a4b2bb1db4d57ca31.png"},{"id":95940017,"identity":"7a01795a-cda1-4355-81f9-60144928b5c9","added_by":"auto","created_at":"2025-11-14 16:08:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":117222,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHearing assessments for left ear (A) and right ear (B) after rimegepant treatment.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were no significant differences in air and bone conduction in the left ear. In the right ear, bone conduction showed no significant difference, while air conduction significantly improved (\u003cem\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/em\u003e=0.0148).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8009385/v1/48472c74a2ccf77e09d6eaf9.png"},{"id":99172381,"identity":"c9267feb-e216-4bfc-8699-828bb1dc1839","added_by":"auto","created_at":"2025-12-29 16:08:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1436139,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8009385/v1/f624b2fe-7437-41a9-bb98-9efae286cc3a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effectiveness of Rimegepant in Vestibular Migraine: A Prospective Self-controlled Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eVestibular migraine (VM) is a syndrome characterized by recurrent episodes of vestibular symptoms. Globally, VM is the second most common cause of episodic vertigo [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. According to the latest guidelines [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], the diagnosis of VM is based on four criteria: (1) at least five attacks of moderate or severe vestibular symptoms, defined by the B\u0026aacute;r\u0026aacute;ny Society [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]; (2) a history of migraine per the International Classification of Headache Disorders, third edition (ICHD-3); (3) at least half of the attacks accompanied by one of the following symptoms: headache, photophobia, phonophobia, or visual aura; and (4) symptoms that cannot be better explained by other ICHD-3 diagnoses or other vestibular disorders. VM\u0026rsquo;s lifetime prevalence is 1% in Germany [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], versus 2.7% in the United States [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Notably, VM cases account for up to 30% of patients seeking treatment for episodic dizziness [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In China, a study reported that 9.2% patients with dizziness or vertigo were diagnosed with VM, accounting for 54.1% of patients with central vestibular disorders (CVD) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite the large number of VM patients, there is a lack of effective therapeutic drugs. Some studies suggest that VM patients may benefit from migraine treatments, including acute medications (such as gepants [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], triptans [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and vestibular inhibitor [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]) and preventive treatments (e.g., calcitonin gene-related peptide (CGRP) medications [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], β-blockers [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and calcium channel blockers [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]). Currently, VM treatment relies primarily on traditional medications, which often have poor efficacy, delayed onset (4\u0026ndash;6 weeks), and considerable adverse effects (AEs) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Meanwhile, evidence supporting the efficacy of these traditional medications for VM is limited. In 2023, Cochrane Reviews concluded that there is insufficient evidence to support the use of acute-care or prophylactic medications for VM [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], with only one placebo-controlled randomized clinical trial (RCT) on prophylaxis included [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Other studies have shown that triptans are ineffective in VM treatment and do not improve vertigo attacks [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In contrast, Russo et al. recently reported that CGRP monoclonal antibodies (mAbs) may improve both vertigo and headache in a prospective observational cohort study [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Anti-CGRP drugs, including gepants and mAbs, offer promising potential for overcoming the current treatment impasse.\u003c/p\u003e\u003cp\u003eIn preclinical studies, gepants have shown encouraging effects in motion sickness therapy. For example, olcegepant significantly alleviated nausea in mouse models of migraine induced by CGRP and sodium nitroprusside (SNP) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and improved vestibular function through the PKC/ERK/CREB pathway in a rat model of chronic migraine [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Hoskin et al. reported a retrospective clinical analysis of anti-CGRP agents for VM, and while the study size was small (only two patients treated with ubrogepant), the findings suggested that anti-CGRP drugs could be a potential treatment option for VM [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additionally, anti-CGRP drugs have demonstrated potential preventive benefits in RCTs [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Rimegepant, a first-generation anti-CGRP agent, showed significant therapeutic efficacy in acute migraine attacks in a multicenter, randomized, controlled, double-blind clinical trial [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, its efficacy in alleviating vestibular symptoms in VM remains unclear. Therefore, the aim of our study was to assess the effectiveness of rimegepant in VM patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and participants\u003c/h2\u003e\u003cp\u003eThis prospective multicenter cohort study aimed to assess the real-world effectiveness of rimegepant in VM. The study was conducted at Sir Run Run Shaw Hospital and the Second Affiliated Hospital, Zhejiang University School of Medicine, with approval from the institutional ethics committee. All participants provided written informed consent prior to any study-related procedures. Inclusion criteria were: diagnosis consistent with the B\u0026aacute;r\u0026aacute;ny Society criteria for VM or probable VM (pVM) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], age\u0026thinsp;\u0026ge;\u0026thinsp;18 years, no prior use of anti-CGRP drugs. Exclusion criteria included other potential vestibular diseases, incomplete questionnaires or follow-up, pregnancy or lactation in women, unwillingness to fille e-diaries or questionnaires, and serious medical or psychiatric conditions. Two attending physicians confirmed the diagnosis. Ultimately, 33 participants were included.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy outcomes\u003c/h3\u003e\n\u003cp\u003eThe clinical characteristics, demographics, and medical histories of all participants were recorded. A total of 33 patients were included in the analysis out of 106 VM or pVM cases. At baseline, all 33 patients completed the following assessments: Dizziness Handicap Inventory (DHI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Headache Impact Test-6 (HIT-6), Vertigo Symptom Scale\u0026ndash;Short Form (VSS-SF), and Activities-specific Balance Confidence Scale (ABC). Patients were followed up for 4 weeks, during which they were administered rimegepant at 75 mg every other day. Follow-up visits occurred every two weeks. At each visit, the numbers of vestibular symptom days and headache days, and medications taken during the preceding 14 days were recorded. The week-2 visit may be conducted by telephone, the week-4 visit must be face-to-face, and all the scales listed above were re-administered at Week 4. The definition of vestibular symptoms referred to the criteria of the B\u0026aacute;r\u0026aacute;ny Society [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Hearing assessments were performed before and after treatment, and complete air and bone conduction values were recorded for 22 patients. Adverse events (AEs) related to rimegepant were also recorded for safety assessment.\u003c/p\u003e\u003cp\u003eThe primary outcome was reduction in mean number of vestibular symptom days over 4 weeks postdosing. Secondary outcomes included mean number of headache days over 4 weeks postdosing, mean number of vestibular symptom days every 2 weeks, mean number of headache days every 2 weeks, and changes in assessment scale scores related to vertigo, dizziness, mood, anxiety, and hearing.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eAll data were recorded in Microsoft Excel (version 16.7). Baseline variables were summarized using descriptive analysis. Categorical variables were expressed as frequency and percentage, and continuous variables as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). The McNemar\u0026rsquo;s test was applied for categorical data. Normality was assessed by normality and log-normality tests. For non-normally distributed data, the Wilcoxon Mann\u0026ndash;Whitney U test was applied; otherwise, two-way paired or unpaired t-test was used. The Wilcoxon signed-rank test was performed for data with unequal variance. Cohen\u0026rsquo;s d was used to calculate effect sizes. For comparisons involving multiple variables, one-way ANOVA was conducted. Statistical analyses were conducted with SPSS (version 22.0, IBM), and data visualization was performed with GraphPad Prism (version 9.5.1). A two-tailed P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eParticipant screening and clinical features in the VM cohort\u003c/h2\u003e\u003cp\u003eA total of 106 patients with VM or pVM were initially considered for inclusion in the current study. Of these, 55 were enrolled, while 16 patients declined follow-up, 11 used other anti-CGRP drugs, and 24 continued alternative therapies. During the follow-up period, 1 patient was excluded due to the influence of other comorbidities, 11 due to improper medication use, 4 due to loss to follow-up, and 6 for unknown reasons. Ultimately, 33 patients were included in the analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe 33 enrolled participants had a mean age of 45.19 years, with 78.8% being female (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Before treatment, the monthly frequencies of vestibular symptoms and headache were 16.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.29 and 10.55\u0026thinsp;\u0026plusmn;\u0026thinsp;9.10, respectively. In addition, mean DHI and VSS-SF scores were 47.58\u0026thinsp;\u0026plusmn;\u0026thinsp;25.67 and 14.64\u0026thinsp;\u0026plusmn;\u0026thinsp;10.12, respectively. Mean GAD-7 and PHQ-9 scores were 6.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.67 and 7.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.61, respectively, while HIT-6 and ABC scores were 61.27\u0026thinsp;\u0026plusmn;\u0026thinsp;8.19 and 67.42\u0026thinsp;\u0026plusmn;\u0026thinsp;30.76, respectively. These findings indicated that VM patients with vestibular dysfunction and headache experienced substantial psychological distress and impairment in daily life.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45.19\u0026thinsp;\u0026plusmn;\u0026thinsp;15.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (21.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (78.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47.58\u0026thinsp;\u0026plusmn;\u0026thinsp;25.67\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-P\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.82\u0026thinsp;\u0026plusmn;\u0026thinsp;8.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-E\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.61\u0026thinsp;\u0026plusmn;\u0026thinsp;9.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19.15\u0026thinsp;\u0026plusmn;\u0026thinsp;10.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-Mild\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (24.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-Moderate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (39.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-Severe\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (36.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGAD-7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.67\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePHQ-9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIT-6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61.27\u0026thinsp;\u0026plusmn;\u0026thinsp;8.19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVSS-SF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.64\u0026thinsp;\u0026plusmn;\u0026thinsp;10.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVSS-SF_F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.15\u0026thinsp;\u0026plusmn;\u0026thinsp;8.70\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVSS-SF_E\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eABC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67.42\u0026thinsp;\u0026plusmn;\u0026thinsp;30.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVestibular symptoms (days per month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeadache (days per month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.55\u0026thinsp;\u0026plusmn;\u0026thinsp;9.10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eDHI, Dizziness Handicap Inventory; DHI-P, DHI- Physical; DHI-E, DHI-Emotional; DHI-F, DHI- Functional; GAD-7, Generalized Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9; HIT-6, Headache Impact Test-6; VSS-SF, Vertigo Symptom Scale\u0026ndash;Short Form; VSS-SF_F, VSS-Functional; VSS-SF_E, VSS-Emotional; ABC, Activities-specific Balance Confidence Scale.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eRimegepant provides short-term relief of vestibular symptoms and headache in VM\u003c/h2\u003e\u003cp\u003eTo investigate the early onset of efficacy, the 2-week frequencies of vestibular symptoms and headache were assessed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). During the rimegepant treatment period, both mean vestibular symptom and headache days showed significant decreases at 2 weeks (vestibular symptoms: 5.68\u0026thinsp;\u0026plusmn;\u0026thinsp;4.38 \u003cem\u003evs.\u003c/em\u003e 8.18\u0026thinsp;\u0026plusmn;\u0026thinsp;4.65, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;=\u0026thinsp;0.0391; headache: 2.95\u0026thinsp;\u0026plusmn;\u0026thinsp;3.91 \u003cem\u003evs.\u003c/em\u003e 5.27\u0026thinsp;\u0026plusmn;\u0026thinsp;4.55, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;=\u0026thinsp;0.0318) and at 4 weeks (vestibular symptoms: 3.21\u0026thinsp;\u0026plusmn;\u0026thinsp;3.77 \u003cem\u003evs.\u003c/em\u003e 8.18\u0026thinsp;\u0026plusmn;\u0026thinsp;4.65, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; headache: 2.06\u0026thinsp;\u0026plusmn;\u0026thinsp;2.89 \u003cem\u003evs.\u003c/em\u003e 5.27\u0026thinsp;\u0026plusmn;\u0026thinsp;4.55, \u003cb\u003eP\u003c/b\u003e\u0026thinsp;=\u0026thinsp;0.0020).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eRimegepant demonstrates improvements in vestibular and psychological outcomes and hearing after 4 weeks\u003c/h3\u003e\n\u003cp\u003eAfter 4 weeks of rimegepant treatment, VM patients showed relief of vestibular symptoms and improvement in psychological well-being (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The monthly frequencies of vestibular symptoms (7.88\u0026thinsp;\u0026plusmn;\u0026thinsp;8.01) and headache (4.67\u0026thinsp;\u0026plusmn;\u0026thinsp;5.19) decreased significantly, with large effect sizes (vestibular symptoms: \u003cb\u003eP\u003c/b\u003e\u0026thinsp;=\u0026thinsp;0.0002, Cohen\u0026rsquo;s d\u0026thinsp;=\u0026thinsp;0.98; headache: P\u0026thinsp;=\u0026thinsp;0.0062, Cohen\u0026rsquo;s d\u0026thinsp;=\u0026thinsp;0.79). Of these patients, 63.6% and 70.4% experienced a 50% reduction in vestibular symptoms and headache, respectively. Furthermore, DHI scores (20.24\u0026thinsp;\u0026plusmn;\u0026thinsp;24.53), including the physical (6.42\u0026thinsp;\u0026plusmn;\u0026thinsp;6.78), emotional (5.76\u0026thinsp;\u0026plusmn;\u0026thinsp;8.35), and functional (8.06\u0026thinsp;\u0026plusmn;\u0026thinsp;10.52) subdomains, were significantly improved compared with baseline, with large effect sizes (\u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Cohen\u0026rsquo;s d\u0026thinsp;\u0026gt;\u0026thinsp;0.8). VSS-SF scores (8.42\u0026thinsp;\u0026plusmn;\u0026thinsp;9.01), comprising the functional (dizziness and balance disorders) (7.00\u0026thinsp;\u0026plusmn;\u0026thinsp;7.28) and emotional (autonomic symptoms) (1.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95) domains, also showed a significant improvement with moderate effect sizes (\u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Cohen\u0026rsquo;s d\u0026thinsp;\u0026gt;\u0026thinsp;0.5). Similarly, GAD-7 (3.30\u0026thinsp;\u0026plusmn;\u0026thinsp;4.63) and PHQ-9 (4.15\u0026thinsp;\u0026plusmn;\u0026thinsp;4.49) scores demonstrated significant reductions, indicating improved psychological status (\u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Cohen\u0026rsquo;s d\u0026thinsp;\u0026gt;\u0026thinsp;0.5). In addition, both HIT-6 (50.00\u0026thinsp;\u0026plusmn;\u0026thinsp;10.26) and ABC (87.41\u0026thinsp;\u0026plusmn;\u0026thinsp;16.09) scores improved significantly after treatment (\u003cb\u003eP\u003c/b\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOutcomes after a 4-week rimegepant treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 weeks\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDifference \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eEffect size\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e47.58\u0026thinsp;\u0026plusmn;\u0026thinsp;25.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e20.24\u0026thinsp;\u0026plusmn;\u0026thinsp;24.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-27.33 (-36.54, -18.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-P\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e13.82\u0026thinsp;\u0026plusmn;\u0026thinsp;8.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e6.42\u0026thinsp;\u0026plusmn;\u0026thinsp;6.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-7.39 (-10.24, -4.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-E\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e14.61\u0026thinsp;\u0026plusmn;\u0026thinsp;9.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5.76\u0026thinsp;\u0026plusmn;\u0026thinsp;8.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-8.85 \u003cb\u003e(\u003c/b\u003e-12.02, -5.68\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDHI-F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e19.15\u0026thinsp;\u0026plusmn;\u0026thinsp;10.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e8.06\u0026thinsp;\u0026plusmn;\u0026thinsp;10.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-11.09 (-15.23, -6.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGAD-7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e6.64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3.33 (-5.08, -1.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0086\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePHQ-9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e7.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e4.15\u0026thinsp;\u0026plusmn;\u0026thinsp;4.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3.33 (-5.21, -1.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0071\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIT-6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e61.27\u0026thinsp;\u0026plusmn;\u0026thinsp;8.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e50.00\u0026thinsp;\u0026plusmn;\u0026thinsp;10.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-11.27 (-15.20, -7.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVSS-SF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e14.64\u0026thinsp;\u0026plusmn;\u0026thinsp;10.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e8.42\u0026thinsp;\u0026plusmn;\u0026thinsp;9.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-6.21 (-10.24, -2.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0069\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVSS-SF_F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e12.15\u0026thinsp;\u0026plusmn;\u0026thinsp;8.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7.00\u0026thinsp;\u0026plusmn;\u0026thinsp;7.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-5.15 (-8.45, -1.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0085\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVSS-SF_E\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e2.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1.06 (-1.98, -0.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0158\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eABC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e67.42\u0026thinsp;\u0026plusmn;\u0026thinsp;30.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e87.41\u0026thinsp;\u0026plusmn;\u0026thinsp;16.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.98 (9.96, 30.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0050\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e-0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVestibular symptoms\u003c/p\u003e\u003cp\u003e(days per month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e16.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7.88\u0026thinsp;\u0026plusmn;\u0026thinsp;8.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-8.48 (-10.92, -6.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0002\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeadache\u003c/p\u003e\u003cp\u003e(days per month)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e10.55\u0026thinsp;\u0026plusmn;\u0026thinsp;9.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e4.67\u0026thinsp;\u0026plusmn;\u0026thinsp;5.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-5.88 (-8.40, -3.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.0062\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.79\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eDHI, Dizziness Handicap Inventory; DHI-P, DHI- Physical; DHI-E, DHI-Emotional; DHI-F, DHI- Functional; GAD-7, Generalized Anxiety Disorder-7; PHQ-9, Patient Health Questionnaire-9; HIT-6, Headache Impact Test-6; VSS-SF, Vertigo Symptom Scale\u0026ndash;Short Form; VSS-SF_F, VSS-Functional; VSS-SF_E, VSS-Emotional; ABC, Activities-specific Balance Confidence Scale.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e Difference expressed as mean value and 95% confidence interval (CI).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMoreover, hearing assessments of air and bone conduction were performed for 22 patients using PTA (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In the left ear, 12 patients showed reduced air conduction and 7 displayed reduced bone conduction. In the right ear, 16 patients had decreased air conduction and 15 had reduced bone conduction. Notably, air conduction in the right ear showed a significant improvement (\u003cb\u003eP\u003c/b\u003e\u0026thinsp;=\u0026thinsp;0.0148).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCollectively, these findings suggest that rimegepant provides relief of vestibular symptoms and improves psychological state in patients with VM, with an early onset of efficacy observed at 2 weeks.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this cohort study, rimegepant was effective in patients with VM by improving both vestibular symptoms and psychological well-being. This is the first cohort study to evaluate rimegepant for VM treatment in China. Currently, commonly recommended drugs for VM prevention primarily aim to relieve symptoms or improve the quality of life. These mainly include tricyclic antidepressants (e.g., nortriptyline [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and venlafaxine [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]), β-blockers (e.g., propranolol [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]), and antiepileptic drugs (topiramate and valproic acid [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]), which are known to improve vertigo and headache in VM. Bayer et al. investigated the effects of metoprolol succinate (a β-blocker) over 6 months in VM patients, reporting a reduction of 1.4 days in monthly vertigo attacks [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Liu et al. assessed three drugs (venlafaxine, flunarizine, and valproic acid), reporting reductions of 2.74 days (venlafaxine), 0.8 days (flunarizine), and 2.75 days (valproic acid) in vertigo attacks after 3 months of treatment [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In this study, rimegepant reduced monthly vertigo days by 8.48 after only one month of use, suggesting it may offer superior therapeutic effects with a fast onset. In a small study of rimegepant in patients with concurrent vestibular migraine (VM) and M\u0026eacute;ni\u0026egrave;re\u0026rsquo;s disease (MD), all five participants administered rimegepant 48-hourly as preventive therapy experienced complete resolution of vertigo during the 8-month treatment period, suggesting favorable efficacy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Another small head-to-head trial confirmed a good efficacy and safety profile for galcanezumab in VM [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These findings are consistent with our results, suggesting that CGRP-targeted therapies may be highly effective for vestibular migraine. As for therapeutic efficacy, since these traditional migraine preventive medications are not specifically designed for VM, their therapeutic efficacy remains controversial. For example, a meta-analysis of 828 VM patients demonstrated significant benefits for valproic acid, propranolol, and venlafaxine [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In contrast, other studies have reported the poor effects and tolerability of these agents in VM [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Furthermore, adverse events (AEs) associated with these drugs are common and, in some cases, serious. Nortriptyline may cause dry mouth, constipation, orthostatic hypotension, and/or confusion. Venlafaxine can lead to elevated blood pressure and worsened headache. Propranolol should be used cautiously in patients with angiocardiopathy or asthma due to its β-blocker effects. Common side effects of topiramate include cognitive impairment, sensory disturbances, and mood disorders, while valproic acid is often associated with weight gain or tremors. In this study, no patient reported any moderate or severe drug-related adverse events, and there was no treatment discontinuation due to side effects; in addition, all adverse reactions were mild and required no additional intervention. Nonetheless, there is an urgent need for more effective and better-tolerated therapies for VM. Our findings support the effectiveness of rimegepant and provide valuable clinical evidence for its use in VM.\u003c/p\u003e\u003cp\u003eIn this study, rimegepant demonstrated effectiveness in improving both vestibular symptoms and headache at an early time. Significant improvements with large effect sizes were detected in clinical assessments, including DHI and VSS-SF scores. The DHI evaluates the quality of life in VM patients across three domains: functional, emotional, and physical [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The VSS-SF assesses the severity and frequency of vestibular symptoms [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. These improvements reflect meaningful symptom relief. Notably, other studies have also reported that different medications can reduce DHI scores. For example, G\u0026ouml;r\u0026uuml;r et al. found that botulinum toxin, propranolol, amitriptyline, and flunarizine reduced DHI scores [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, their effects took up to three months, whereas rimegepant in this study showed significant reductions after only one month of treatment. Additionally, the VSS-SF showed excellent improvements. While the focus is often on VM symptoms, psychological distress should also be considered. It was reported that up to 50% of patients with vertigo symptoms have psychological disorders [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In this study, the GAD-7 and PHQ-9 scales were used to assess anxiety and depression in VM patients. The GAD-7 scale is primarily used to screen for and assess the severity of anxiety disorders [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], while the PHQ-9 scale is used to screen for and assess the severity of depressive symptoms [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. The rapid relief of vestibular symptoms in this study was associated with improvements in anxiety and depression. For quality of life assessments, the HIT-6 and ABC scales were used. The HIT-6 scale evaluates the disease burden and the quality of life [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], while the ABC scale assesses the confidence in maintaining balance during daily activities [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Improvements in both vestibular symptoms and psychological status contributed to the observed improvements in the quality of life. While reductions were also observed in VSS-SF, GAD-7, and PHQ-9 scores, the effect sizes were moderate. We speculate that this may be because approximately half of the examined patients had long-standing, severe anxiety and significant impairment in daily life, suggesting that a longer treatment course might be required for individuals with severe psychological comorbidities. Additionally, the predominance of middle-aged female patients (mean age: 42.3 years) raises the possibility that hormonal fluctuations may have affected treatment outcomes [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFurthermore, hearing assessments through PTA testing were conducted. In over half of the assessed patients, hearing test values were reduced in both ears. While the improvements were modest, air conduction in the right ear showed a significant improvement. This suggests that rimegepant may exert an effect on hearing, potentially explained by the distribution of CGRP in the inner ear. It has been reported that CGRP and its receptors are expressed at moderate-to-high levels in the central nervous system and inner ear [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Additionally, Rahman et al. reported that CGRP can alter auditory function, with these effects reversed by CGRP antagonists [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. In contrast, CGRP mAbs currently require injection [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], making oral administration of rimegepant a more convenient option. However, a significant improvement was observed in this study only in right-ear air-conduction thresholds, with no significant benefit detected in left-ear air conduction or bilateral bone conduction. We speculate that audiological improvement may require a prolonged treatment, and studies with extended therapy and follow-up are therefore warranted.\u003c/p\u003e\u003cp\u003eThis study had several limitations. First, it had a single-arm design in which efficacy was assessed through self-comparison before and after treatment. Future trials should include placebo-controlled groups to strengthen validity. Second, the sample size was relatively small, and all participants were Chinese. Studies with larger cohorts including different races and regions are warranted to better generalize the therapeutic effects of rimegepant. Third, this analysis used a short treatment period of 4 weeks, with preventive effects evaluated as early as 2 weeks; further research is needed to assess the efficacy of rimegepant in relieving acute symptoms and long-term preventive efficacy. Finally, this investigation focused on a single CGRP antagonist. Comparative studies including traditional agents (e.g., SSRIs, valproic acid, propranolol) and anti-CGRP mAbs are required to fully delineate relative efficacy and safety profiles.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, rimegepant provides meaningful relief of vestibular symptoms and improves psychological well-being in patients with VM, with clinical benefits evident as early as 2 weeks. These findings support the potential of rimegepant as a valuable therapeutic option for VM.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVestibular migraine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eDizziness Handicap Inventory\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGAD-7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eGeneralized Anxiety Disorder-7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePHQ-9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003ePatient Health Questionnaire-9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIT-6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eHeadache Impact Test-6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVSS-SF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eVertigo Symptom Scale\u0026ndash;Short Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eABC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eActivities-specific Balance Confidence Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICHD-3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eInternational Classification of Headache Disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003ePure tone audiometry\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCVD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eCentral vestibular disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCGRP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eCalcitonin gene-related peptide\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRCT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eRandomized clinical trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003emAbs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eMonoclonal antibodies\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSNP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eSodium nitroprusside\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAEs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eAdverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003epVM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eProbable VM\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eConfidence interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSSRIs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eSerotonin reuptake inhibitors\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTVS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eTrigeminovascular system\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eVestibular ganglia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 17.4603%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82.5397%;\"\u003e\n \u003cp\u003eCortical spreading depression\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the medical staff who assisted in the outpatient work and are grateful to Dr. Chen Guoqiao for guidance regarding the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSJY and LKM: Conceptualization, Formal analysis and Methodology. FJX and ZMT: Writing - Original Draft. RZW, LLX, GLL, XYH, ZZX, YMN and HJH: Investigation, Resources, Data Curation. SJY,\u003csup\u003e\u0026nbsp;\u003c/sup\u003eFJX and ZMT contributed equally to this work. All authors contributed to the final manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Key Research and Development Program of Zhejiang Province (Grant No. 2024C03007).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFurther information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided written informed consent prior to enrollment. They were notified that deidentified study-related data would be used in compliance with local regulations on privacy and data protection. The study protocol received approval from the Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eEspinosa-Sanchez JM and Lin C-C (2025) Editorial: Vestibular migraine\u003cem\u003e.\u003c/em\u003e Frontiers in Neurology Volume 16 - 2025\u003c/li\u003e\n\u003cli\u003eLempert T, Olesen J, Furman J, et al (2022) Vestibular migraine: Diagnostic criteria1\u003cem\u003e.\u003c/em\u003e J Vestib Res 32:1-6\u003c/li\u003e\n\u003cli\u003eBisdorff A, Von Brevern M, Lempert T, et al (2009) Classification of vestibular symptoms: towards an international classification of vestibular disorders\u003cem\u003e.\u003c/em\u003e J Vestib Res 19:1-13\u003c/li\u003e\n\u003cli\u003eNeuhauser HK, Radtke A, von Brevern M, et al 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23:35\u003c/li\u003e\n\u003cli\u003eHoskin JL and Fife TD (2021) New Anti-CGRP Medications in the Treatment of Vestibular Migraine\u003cem\u003e.\u003c/em\u003e Front Neurol 12:799002\u003c/li\u003e\n\u003cli\u003eSharon JD, Krauter R, Chae R, et al (2024) A placebo controlled, randomized clinical trial of galcanezumab for vestibular migraine: The INVESTMENT study\u003cem\u003e.\u003c/em\u003e Headache 64:1264-1272\u003c/li\u003e\n\u003cli\u003eYu S, Kim BK, Guo A, et al (2023) Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial\u003cem\u003e.\u003c/em\u003e Lancet Neurol 22:476-484\u003c/li\u003e\n\u003cli\u003eReploeg MD and Goebel JA (2002) Migraine-associated dizziness: patient characteristics and management options\u003cem\u003e.\u003c/em\u003e Otol Neurotol 23:364-371\u003c/li\u003e\n\u003cli\u003eSalviz M, Yuce T, Acar H, et al (2016) Propranolol and venlafaxine for vestibular migraine prophylaxis: A randomized controlled trial\u003cem\u003e.\u003c/em\u003e Laryngoscope 126:169-174\u003c/li\u003e\n\u003cli\u003eVan Ombergen A, Van Rompaey V, Van de Heyning P, et al (2015) Vestibular migraine in an otolaryngology clinic: prevalence, associated symptoms, and prophylactic medication effectiveness\u003cem\u003e.\u003c/em\u003e Otol Neurotol 36:133-138\u003c/li\u003e\n\u003cli\u003eBisdorff A, Andr\u0026eacute;e C, Vaillant M, et al (2010) Headache-associated dizziness in a headache population: prevalence and impact\u003cem\u003e.\u003c/em\u003e Cephalalgia 30:815-820\u003c/li\u003e\n\u003cli\u003eLiu F, Ma T, Che X, et al (2017) The Efficacy of Venlafaxine, Flunarizine, and Valproic Acid in the Prophylaxis of Vestibular Migraine\u003cem\u003e.\u003c/em\u003e Front Neurol 8:524\u003c/li\u003e\n\u003cli\u003eHegemann SCA and Schell A (2025) Treating Meni\u0026egrave;re\u0026apos;s disease with rimegepant\u003cem\u003e.\u003c/em\u003e Swiss Med Wkly 155:4147\u003c/li\u003e\n\u003cli\u003eChen JJ, Zeng BS, Su KP, et al (2023) Network Meta-analysis of Different Treatments for Vestibular Migraine\u003cem\u003e.\u003c/em\u003e CNS Drugs 37:837-847\u003c/li\u003e\n\u003cli\u003eChu H, Wang Y, Ling X, et al (2023) Prophylactic treatments for vestibular migraine: a systematic review and network meta-analysis of randomized clinical trials\u003cem\u003e.\u003c/em\u003e Front Pharmacol 14:1332973\u003c/li\u003e\n\u003cli\u003eJacobson GP and Newman CW (1990) The development of the Dizziness Handicap Inventory\u003cem\u003e.\u003c/em\u003e Arch Otolaryngol Head Neck Surg 116:424-427\u003c/li\u003e\n\u003cli\u003eWilhelmsen K, Strand LI, Nordahl SHG, et al (2008) Psychometric properties of the Vertigo symptom scale - Short form\u003cem\u003e.\u003c/em\u003e BMC Ear Nose Throat Disord 8:2\u003c/li\u003e\n\u003cli\u003eG\u0026ouml;r\u0026uuml;r K, G\u0026uuml;r H, İsmi O, et al (2022) The effectiveness of propranolol, flunarizine, amitriptyline and botulinum toxin in vestibular migraine complaints and prophylaxis: a non-randomized controlled study\u003cem\u003e.\u003c/em\u003e Braz J Otorhinolaryngol 88:975-981\u003c/li\u003e\n\u003cli\u003eLahmann C, Henningsen P, Brandt T, et al (2015) Psychiatric comorbidity and psychosocial impairment among patients with vertigo and dizziness\u003cem\u003e.\u003c/em\u003e J Neurol Neurosurg Psychiatry 86:302-308\u003c/li\u003e\n\u003cli\u003eSpitzer RL, Kroenke K, Williams JB, et al (2006) A brief measure for assessing generalized anxiety disorder: the GAD-7\u003cem\u003e.\u003c/em\u003e Arch Intern Med 166:1092-1097\u003c/li\u003e\n\u003cli\u003eKroenke K, Spitzer RL, and Williams JB (2001) The PHQ-9: validity of a brief depression severity measure\u003cem\u003e.\u003c/em\u003e J Gen Intern Med 16:606-613\u003c/li\u003e\n\u003cli\u003eKosinski M, Bayliss MS, Bjorner JB, et al (2003) A six-item short-form survey for measuring headache impact: the HIT-6\u003cem\u003e.\u003c/em\u003e Qual Life Res 12:963-974\u003c/li\u003e\n\u003cli\u003ePowell LE and Myers AM (1995) The Activities-specific Balance Confidence (ABC) Scale\u003cem\u003e.\u003c/em\u003e J Gerontol A Biol Sci Med Sci 50a:M28-34\u003c/li\u003e\n\u003cli\u003eSierra I, Pyfrom S, Weiner A, et al (2023) Unusual X chromosome inactivation maintenance in female alveolar type 2 cells is correlated with increased numbers of X-linked escape genes and sex-biased gene expression\u003cem\u003e.\u003c/em\u003e Stem Cell Reports 18:489-502\u003c/li\u003e\n\u003cli\u003eDudek A, Sienkiewicz W, and Kaleczyc J (2012) Immunohistochemical characterization of neurons in the vestibular ganglion (Scarpa\u0026apos;s ganglion) of the pig\u003cem\u003e.\u003c/em\u003e Pol J Vet Sci 15:499-507\u003c/li\u003e\n\u003cli\u003eHolland PR, Saengjaroentham C, and Vila-Pueyo M (2019) The role of the brainstem in migraine: Potential brainstem effects of CGRP and CGRP receptor activation in animal models\u003cem\u003e.\u003c/em\u003e Cephalalgia 39:390-402\u003c/li\u003e\n\u003cli\u003eRahman SM, Hauser C, Faucher S, et al (2024) A Vestibular Challenge Combined with Calcitonin Gene-Related Peptide (CGRP) Promotes Anxiety-Like Behaviors\u003cem\u003e.\u003c/em\u003e eNeuro 11\u003c/li\u003e\n\u003cli\u003eRahman SM, Faucher S, Jonnala R, et al (2025) Systemic calcitonin gene-related peptide modifies auditory and vestibular end organ electrical potentials, and increases sensory hypersensitivities\u003cem\u003e.\u003c/em\u003e J Neurophysiol 134:107-117\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-journal-of-headache-and-pain","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tjhp","sideBox":"Learn more about [The Journal of Headache and Pain](https://thejournalofheadacheandpain.biomedcentral.com/)","snPcode":"10194","submissionUrl":"https://submission.nature.com/new-submission/10194/3","title":"The Journal of Headache and Pain","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Vestibular migraine, Rimegepant, Real-world, Treatment","lastPublishedDoi":"10.21203/rs.3.rs-8009385/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8009385/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eVestibular migraine (VM) is the second most common cause of episodic vertigo worldwide, yet effective therapeutic options remain limited. This study aimed to assess the clinical effectiveness of rimegepant in patients with VM.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA total of 33 VM cases were enrolled in this multicenter, prospective self-controlled cohort study, screened from an initial pool of 106 patients. Mean 4-week days of vestibular symptom or headache, along with Dizziness Handicap Inventory (DHI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Headache Impact Test-6 (HIT-6), Vertigo Symptom Scale\u0026ndash;Short Form (VSS-SF), Activities-specific Balance Confidence Scale (ABC) scores, and hearing sensitivities were compared between pre-dosing and postdosing of rimegepant over a 4-week follow-up.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAt baseline, participants exhibited a high symptom burden, with elevated DHI, VSS-SF, GAD-7, PHQ-9, and HIT-6 scores and low ABC scores. After rimegepant treatment, there were substantial reductions in monthly vestibular symptom days and headache days (differences: vestibular symptoms, -8.48; headache, -5.88). Totally 63.6% and 70.4% of the patients experienced a 50% reduction in vestibular symptom days and headache days, respectively. Notably, these improvements were already apparent at 2 weeks, indicating early onset of efficacy. Additionally, rimegepant treatment led to significant improvements in vestibular function (differences: DHI, -27.33; VSS-SF, -6.21), psychological status (differences: GAD-7, -3.33; PHQ-9, -3.33), and quality of life (differences: HIT-6, -11.27; ABC, 19.98). Pure tone audiometry (PTA) results also indicated improvements in hearing.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eRimegepant provides relief of vestibular symptoms and improves psychological well-being and hearing in patients with VM, with efficacy evident as early as 2 weeks.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e\u003cp\u003eNCT04939922\u003c/p\u003e","manuscriptTitle":"Effectiveness of Rimegepant in Vestibular Migraine: A Prospective Self-controlled Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 16:08:25","doi":"10.21203/rs.3.rs-8009385/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-18T05:06:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-15T17:25:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-15T01:54:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3870490602537731075055288014287279082","date":"2025-11-07T23:47:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70036729637381664854730226694809892943","date":"2025-11-06T01:18:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-05T09:53:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-04T14:37:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-04T13:14:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Journal of Headache and Pain","date":"2025-11-02T07:07:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-journal-of-headache-and-pain","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tjhp","sideBox":"Learn more about [The Journal of Headache and Pain](https://thejournalofheadacheandpain.biomedcentral.com/)","snPcode":"10194","submissionUrl":"https://submission.nature.com/new-submission/10194/3","title":"The Journal of Headache and Pain","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2a86a28a-6b5e-4ec7-9f93-44d3eb62213d","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-29T16:03:29+00:00","versionOfRecord":{"articleIdentity":"rs-8009385","link":"https://doi.org/10.1186/s10194-025-02243-5","journal":{"identity":"the-journal-of-headache-and-pain","isVorOnly":false,"title":"The Journal of Headache and Pain"},"publishedOn":"2025-12-22 15:58:27","publishedOnDateReadable":"December 22nd, 2025"},"versionCreatedAt":"2025-11-14 16:08:25","video":"","vorDoi":"10.1186/s10194-025-02243-5","vorDoiUrl":"https://doi.org/10.1186/s10194-025-02243-5","workflowStages":[]},"version":"v1","identity":"rs-8009385","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8009385","identity":"rs-8009385","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}