CGRP-Targeting Therapies in Vestibular Migraine: A Synthesis of Observational Evidence with Direction-of-Effect Analysis

Background: Vestibular migraine (VM) is a common but underdiagnosed cause of episodic vertigo lacking evidence-based preventive treatments. Calcitonin gene-related peptide (CGRP) plays a central role in migraine pathogenesis and is expressed in vestibular structures, providing a rationale for CGRP-targeting therapies in VM. However, available evidence has not been systematically synthesized. Methods: We conducted a structured synthesis of studies evaluating CGRP-targeting therapies (monoclonal antibodies and gepants) in adults with definite/probable VM. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science. Eligible studies included randomized controlled trials, prospective/retrospective cohorts, and case series (≥10 patients) reporting quantitative outcomes. A two-tier synthesis was prespecified: quantitative meta-analysis where feasible, otherwise narrative synthesis with direction-of-effect analysis. Results: Of 247 records, four observational studies met inclusion criteria (total N ≈ 103 patients). No RCTs were identified. All four studies evaluated CGRP monoclonal antibodies; no gepant studies met inclusion criteria. Outcome reporting was highly heterogeneous. Quantitative meta-analysis was not feasible. Direction-of-effect synthesis showed consistent improvement across all studies for vertigo frequency (4/4), Dizziness Handicap Inventory (2/2), and monthly migraine days (2/2). No serious adverse events were reported. Conclusions: CGRP monoclonal antibodies show a consistent direction of benefit for vestibular symptoms, migraine days, and dizziness handicap in observational VM studies, with a favorable safety profile. However, the absence of RCTs, small samples, lack of control groups, and heterogeneity preclude definitive conclusions. This synthesis highlights a critical evidence gap. Adequately powered, double-blind, placebo-controlled RCTs of CGRP-targeting therapies (both monoclonal antibodies and gepants) are urgently needed.