{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:08:12Z","timestamp":1780578492563,"version":"3.54.1"},"reference-count":19,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>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 (\u226510 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 \u2248 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.<\/jats:p>","DOI":"10.3390\/medsci14020288","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:52:30Z","timestamp":1780573950000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CGRP-Targeting Therapies in Vestibular Migraine: A Synthesis of Observational Evidence with Direction-of-Effect Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2079-2383","authenticated-orcid":false,"given":"Alin","family":"Ciubotaru","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0008-9696","authenticated-orcid":false,"given":"Alexandra","family":"Mastaleru","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4495-4004","authenticated-orcid":false,"given":"Thomas Gabriel","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Grosu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Alexa","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andra","family":"Oancea","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Vamanu","sequence":"additional","affiliation":[{"name":"Basic and Clinical Neuroscience Department, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4860-3324","authenticated-orcid":false,"given":"Adina Maria","family":"Roceanu","sequence":"additional","affiliation":[{"name":"Neurology Department, University Emergency Hospital Bucharest, 020021 Bucharest, Romania"},{"name":"Coordinator of Headache Group of Romanian Society of Neurology, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1441-1751","authenticated-orcid":false,"given":"Andrei Ionut","family":"Cucu","sequence":"additional","affiliation":[{"name":"Emerald Hospital Iasi, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan Ionut","family":"Pana","sequence":"additional","affiliation":[{"name":"Emerald Hospital Bucharest, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-6232","authenticated-orcid":false,"given":"Romica Sebastian","family":"Cozma","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1221-5397","authenticated-orcid":false,"given":"Raluca","family":"Olariu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuciureanu","family":"Dan Iulian","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-9741","authenticated-orcid":false,"given":"Emilian Bogdan","family":"Ignat","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) (2018). The International Classification of Headache Disorders, 3rd edition. Cephalalgia, 38, 1\u2013211.","DOI":"10.1177\/0333102417738202"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3233\/VES-2012-0453","article-title":"Vestibular migraine: Diagnostic criteria","volume":"22","author":"Lempert","year":"2012","journal-title":"J. Vestib. 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