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.

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.

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 < 0.05, Cohen’s d > 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 < 0.05, Cohen’s d > 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 < 0.05, Cohen’s d > 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).

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.

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.

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.