Comparative efficacy of neuromodulation modalities for treatment-refractory obsessive-compulsive disorder: A systematic review, meta-analysis, and network-based analysis

Comparative efficacy of neuromodulation modalities for treatment-refractory obsessive-compulsive disorder: A systematic review, meta-analysis, and network-based analysis | 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 Analysis Comparative efficacy of neuromodulation modalities for treatment-refractory obsessive-compulsive disorder: A systematic review, meta-analysis, and network-based analysis Flavia Venetucci Gouveia, Gavin Elias, Emily Wong, Andrew Yang, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6994731/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Apr, 2026 Read the published version in Nature Mental Health → Version 1 posted You are reading this latest preprint version Abstract Obsessive-compulsive disorder (OCD) is a severe psychiatric illness, with up to 40% of patients remaining refractory to standard treatments. Neuromodulation, including deep brain stimulation (DBS), lesion-based surgery, transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), offers alternative strategies, though their comparative efficacy and network engagement remain uncertain. This meta-analysis of 143 studies involving 2,743 patients showed that the largest improvement effects were observed for lesion-based interventions (standardized mean difference (SMD) = 45.08) and DBS (SMD = 39.73), followed by tDCS (SMD = 28.77) and TMS (SMD = 26.56). Sham-controlled studies confirmed that active treatments outperformed placebo. Functional connectivity analysis of stimulated targets revealed network hubs (e.g., medial prefrontal cortex, anterior limb of the internal capsule, anterior cingulate cortex) as the most effective targets. These findings highlight neuromodulation as a viable therapeutic option and underscore the potential of connectivity-guided approaches in optimizing treatment outcomes. Health sciences/Medical research/Outcomes research Biological sciences/Neuroscience/Diseases of the nervous system Health sciences/Diseases/Psychiatric disorders Treatment-refractory obsessive-compulsive disorder (OCD) neurostimulation meta-analysis deep brain stimulation (DBS) transcranial magnetic stimulation (TMS) transcranial direct current stimulation (tDCS) lesion-based surgery functional connectivity network analysis Full Text Additional Declarations Yes there is potential Competing Interest. A.M.L. is the co-founder of Functional Neuromodulation and a consultant for Boston Scientific, Medtronic and Abbott. All other authors report no conflicts of interest. Cite Share Download PDF Status: Published Journal Publication published 13 Apr, 2026 Read the published version in Nature Mental Health → Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6994731","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Analysis","associatedPublications":[],"authors":[{"id":480379154,"identity":"3253870e-2250-4361-a5de-3c928c0e8d56","order_by":0,"name":"Flavia Venetucci Gouveia","email":"","orcid":"","institution":"Hospital for Sick Children","correspondingAuthor":false,"prefix":"","firstName":"Flavia","middleName":"Venetucci","lastName":"Gouveia","suffix":""},{"id":480379155,"identity":"ae1369cb-86a5-45e5-bb32-ea644ad8c2ef","order_by":1,"name":"Gavin Elias","email":"","orcid":"","institution":"Joint Department of Medical Imaging, University of 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