Evidence for CGRP-Targeted Therapies in Vestibular Migraine Remains Limited Despite Promising Galcanezumab RCT

Vestibular migraine (VM) is a prevalent yet often underdiagnosed cause of episodic vertigo, currently lacking robust evidence-based preventive treatments. Traditional migraine preventatives frequently fall short, leaving many patients with persistent, debilitating symptoms. The calcitonin gene-related peptide (CGRP) pathway is central to migraine pathogenesis and is also expressed in vestibular structures, providing a strong biological rationale for investigating CGRP-targeted therapies in VM. However, data on the efficacy of CGRP monoclonal antibodies (mAbs) or small molecule receptor antagonists (gepants) specifically for VM prevention remain scarce and preliminary, highlighting a critical gap in treatment options.

Researchers conducted a comprehensive review of existing literature on vestibular migraine (VM) prevention using CGRP monoclonal antibodies (mAbs) and gepants. The methodology focused on critically discussing identified studies, emphasizing inherent biases and limitations such as small sample sizes, retrospective study designs, lack of blinding, and potential patient selection biases. The review aimed to synthesize findings regarding treatment response to these CGRP-targeted therapies in VM patients, assessing the strength and reliability of the current evidence base. This approach allowed for a nuanced evaluation of the reported efficacy and safety profiles within the context of methodological rigor.

The review identified 8 studies assessing various CGRP mAbs and gepants for VM prevention. Generally, these studies reported improvements in vestibular symptoms and associated scores. However, a significant limitation across most of these studies was their small sample sizes, coupled with a frequent lack of blinding and control groups, which introduces considerable risk of bias. > A single randomized controlled trial (RCT) provided the strongest evidence, demonstrating a significant treatment response to galcanezumab, with a medium to large effect size ranging between 0.56 and 1.02 for reducing dizzy days. This RCT also reported notable improvements on validated assessment tools, specifically the Dizziness Handicap Inventory (DHI) and the Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI). Despite these promising individual findings, the review concluded that the efficacy established for CGRP-targeted therapies in headache migraine cannot be straightforwardly extrapolated to VM due to distinct underlying pathophysiological mechanisms. There remains a risk that initial effect estimates from less rigorous studies may diminish over time, potentially inflated by novelty effects, patient expectancy, or methodological nuances.