Single-Day versus Once-Daily Transcranial Magnetic Stimulation in Depression: A Propensity-Matched Comparison of Treatment Outcomes

Single-Day versus Once-Daily Transcranial Magnetic Stimulation in Depression: A Propensity-Matched Comparison of Treatment Outcomes | 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 Research Article Single-Day versus Once-Daily Transcranial Magnetic Stimulation in Depression: A Propensity-Matched Comparison of Treatment Outcomes Yosef Berlow, Brooke Marino, Lena Johnson, Madison Stine, Aleksandra Dojnov, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8476115/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Recently, accelerated, pharmacologically augmented regimens for transcranial magnetic stimulation (TMS) have been described, allowing treatment completion in a single day. However, comparisons of outcomes versus once-daily treatment regimens are lacking. Here, we performed a propensity-matched retrospective analysis of individual patient data from a naturalistic sample of patients with major depression who received either a 36-day course of once-daily TMS or single-day of pharmacologically augmented TMS, at a large community practice. Following exclusions, the initial set of 879 patient records yielded a preliminary sample of 114 individuals who received one-day TMS and 330 individuals who underwent 36-day TMS. Propensity-score matching yielded a final analytic sample of N=191 36-day TMS patients, matched to N=106 one-day TMS patients. Remission (PHQ9<5) was defined as the primary outcome measure, with response (≥50% PHQ9 improvement from baseline) as the secondary outcome measure; similar analyses were performed for anxiety symptoms using the GAD7. PHQ9 remission was achieved in 49.1% (52/106) of the single-day TMS patients, versus 25.1% (48/191) of the 36-day patients (χ²=17.473, p <0.0001). PHQ9 response was achieved in 71.7% (76/106) of the single-day TMS patients, versus 56.0% (107/191) of the 36-day patients (χ²=7.084, p =0.0078). Regarding anxiety symptoms, remission (GAD7<5) was achieved in 62.3% (66/106) of the single-day TMS patients, versus 33.0% (63/191) of the 36-day patients(χ²=23.79, p<0.0001). Response was achieved in 72.6% (77/106) of the single-day versus 51.9% (98/189) of the 36-day TMS patients (χ²=12.16, p =0.0005). As previously observed, single-day TMS improvements were not immediate, but instead developed in a delayed fashion over the 6 weeks following treatment, and reaching a plateau at 6-12 weeks post-treatment. This pattern was well-modeled with an exponential-decay function, which yielded superior fits versus linear models in both groups, with the single-day TMS group showing a significantly greater magnitude of effect and rapidity of onset. Observed effects were robust across four slightly different versions of the single-day protocol, varying in target set (dorsolateral ± dorsomedial ± orbitofrontal stimulation), inter-session interval (20 versus 30 min), NMDA agonist (D-cycloserine versus D-serine), and presence/absence of lisdexamfetamine augmentation. Randomized controlled studies will be required for definitive comparisons of single-day to once-daily TMS and for optimization of the regimen. However, the present study suggests that single-day TMS regimens may be capable of achieving outcomes that are not only non-inferior, but indeed superior, to typical 36-day TMS regimens, when delivered under naturalistic conditions in the community. Psychiatry TMS accelerated depression anxiety D-cycloserine augmentation neuroplasticity retrospective propensity-matching exponential-decay function Full Text Additional Declarations The authors declare potential competing interests as follows: BM, LJ, and AD are employed by Ampa Health. MS, HM and WP are employed by NeuroStim TMS Centers. AD is employed by Ampa Health. NW is employed by NeuroStim TMS Centers and holds equity in Arc Health Partners and Ampa Health. FVR has received support from Seedlings Foundation, CIHR, and Brain Canada. He is a volunteer director with the BC Schizophrenia Society board of directors, and he has received in-kind equipment support from Magventure for investigator-initiated research. DV is a co-founder of Ampa Health, and holds equity in Ampa Health and Arc Health Partners. NSP is a consultant to Motif Neuro, and is on the scientific Advisory Boards of Pulvinar Neuro and Grey Matters Neuroscience, and reports royalties from UptoDate Inc; all unrelated to the current work. JD has received grant support from the National Institutes of Health (NIH), Canadian Institutes of Health Research (CIHR), Brain Canada, and the Ontario Brain Institute. He has received in-kind equipment support from Magventure for investigator-initiated research. He has also received consulting fees from TMS Neuro Solutions and Arc Health Partners. He is a co-founder of Ampa Health, and holds equity in Ampa Health and Arc Health Partners. The other authors indicate no disclosures to report. All patients either consented to participate in the Advarra IRB-approved study (in the case of the single-day TMS patients described in this work), or else were subject to an IRB Exempt Determination from Advarra IRB (in the case of the 36-day TMS patients) for the retrospective analysis of their anonymized data. Cite Share Download PDF Status: Posted 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-8476115","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":567040650,"identity":"46d5dc8b-7bb0-4137-9319-0a5548c82fd9","order_by":0,"name":"Yosef Berlow","email":"","orcid":"","institution":"Brown University; VA Providence Healthcare","correspondingAuthor":false,"prefix":"","firstName":"Yosef","middleName":"","lastName":"Berlow","suffix":""},{"id":567040651,"identity":"369f2a81-25f1-4913-ac9d-74b3d362275f","order_by":1,"name":"Brooke Marino","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Brooke","middleName":"","lastName":"Marino","suffix":""},{"id":567040652,"identity":"d8c2ad14-6e6d-47e2-8ae6-982752562c80","order_by":2,"name":"Lena Johnson","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Lena","middleName":"","lastName":"Johnson","suffix":""},{"id":567040653,"identity":"ac1a16ca-8732-46dd-9e60-6af5f2c611c8","order_by":3,"name":"Madison Stine","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Madison","middleName":"","lastName":"Stine","suffix":""},{"id":567040654,"identity":"7494dadf-208f-4c64-9165-1c7c0ff05267","order_by":4,"name":"Aleksandra Dojnov","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Aleksandra","middleName":"","lastName":"Dojnov","suffix":""},{"id":567040655,"identity":"e8294777-e86a-4511-a862-1d56132dca83","order_by":5,"name":"Hannah Matthews","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Hannah","middleName":"","lastName":"Matthews","suffix":""},{"id":567040656,"identity":"4edf29c8-633e-4c3b-8f5d-bdea56154ed1","order_by":6,"name":"Alex Engelbertson","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Alex","middleName":"","lastName":"Engelbertson","suffix":""},{"id":567040657,"identity":"c97b9835-40bc-4558-b0c5-82dd4b0b4956","order_by":7,"name":"Whitley Prater","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Whitley","middleName":"","lastName":"Prater","suffix":""},{"id":567040658,"identity":"9e8542ce-deb7-44e3-99d5-6fc6be2bb2d0","order_by":8,"name":"Farrokh Mansouri","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Farrokh","middleName":"","lastName":"Mansouri","suffix":""},{"id":567040659,"identity":"ba0d889f-1550-4996-bd39-ca50635c48cd","order_by":9,"name":"Amourie Prentice","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Amourie","middleName":"","lastName":"Prentice","suffix":""},{"id":567040660,"identity":"788a9d38-57ff-4aed-a2ac-f5a29e6238f0","order_by":10,"name":"Tasha Morris","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Tasha","middleName":"","lastName":"Morris","suffix":""},{"id":567040661,"identity":"4e2015d1-6751-4cf3-a138-665fbd3a59ed","order_by":11,"name":"Georgine Nanos","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Georgine","middleName":"","lastName":"Nanos","suffix":""},{"id":567040662,"identity":"65684601-1a31-475c-941d-aed61b3c6100","order_by":12,"name":"Nicholas Weiss","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Nicholas","middleName":"","lastName":"Weiss","suffix":""},{"id":567040663,"identity":"1ae5b206-f01e-4a47-b594-82c2a920028e","order_by":13,"name":"Fidel Vila-Rodriguez","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fidel","middleName":"","lastName":"Vila-Rodriguez","suffix":""},{"id":567040664,"identity":"44ba75e2-d77f-4baf-8790-00c96467f034","order_by":14,"name":"Donald A. Vaughn","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Donald","middleName":"A.","lastName":"Vaughn","suffix":""},{"id":567040665,"identity":"4a02ead2-2b42-4115-9bef-b26e63534608","order_by":15,"name":"Noah S. Philip","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Noah","middleName":"S.","lastName":"Philip","suffix":""},{"id":567040666,"identity":"5aabaf53-a2c4-4086-bc49-3a769ad54f4c","order_by":16,"name":"Jonathan Downar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYBACxgYYwZAAFpAjTstBJC3GDGxg2gC/PmQtiQ2EtDC39x78/HGHXR4De/Ix6YKae+kb7jcf+/Bxxx85BvbDD7A6rOdcssTBM8nFDDzP0qRnHCvO3XCMLXnmzDMGxgw8aVitYpyRYyBxsI05sUEix+w2D1sCUAuPMTNvmwFQBLvrgFqMfxxsq4dq+ZeQboDQwv4BhxYzoC2HIVp42xISkLTwYLel54yZxdm244ltPM/Sf/P2JRjOPJaWzDizzdiYjSenAJsWw/Ye4xuVbdWJ/ezJh415viXI8x0+fJjhY5ucHD/78Q1YtTRAGWwYUpgiECCPQ3wUjIJRMApGAQIAAA0CX2DkCTDqAAAAAElFTkSuQmCC","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Jonathan","middleName":"","lastName":"Downar","suffix":""}],"badges":[],"createdAt":"2025-12-29 23:12:01","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8476115/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8476115/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":99795125,"identity":"84cbea13-6c35-4527-9dca-48c704ebc07b","added_by":"auto","created_at":"2026-01-08 13:37:04","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1674624,"visible":true,"origin":"","legend":"","description":"","filename":"PREPRINTBerlowetal.20251Dayvs36DayTMS.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8476115/v1_covered_8f63342f-bd50-42fc-a4d9-829d0795e53c.pdf"}],"financialInterests":"\u003cp\u003eThe authors declare potential competing interests as follows: BM, LJ, and AD are employed by Ampa Health. MS, HM and WP are employed by NeuroStim TMS Centers. AD is employed by Ampa Health. NW is employed by NeuroStim TMS Centers and holds equity in Arc Health Partners and Ampa Health. FVR has received support from Seedlings Foundation, CIHR, and Brain Canada. He is a volunteer director with the BC Schizophrenia Society board of directors, and he has received in-kind equipment support from Magventure for investigator-initiated research. DV is a co-founder of Ampa Health, and holds equity in Ampa Health and Arc Health Partners. NSP is a consultant to Motif Neuro, and is on the scientific Advisory Boards of Pulvinar Neuro and Grey Matters Neuroscience, and reports royalties from UptoDate Inc; all unrelated to the current work. JD has received grant support from the National Institutes of Health (NIH), Canadian Institutes of Health Research (CIHR), Brain Canada, and the Ontario Brain Institute. He has received in-kind equipment support from Magventure for investigator-initiated research. He has also received consulting fees from TMS Neuro Solutions and Arc Health Partners. He is a co-founder of Ampa Health, and holds equity in Ampa Health and Arc Health Partners. The other authors indicate no disclosures to report.\u003c/p\u003e\n\u003cp\u003eAll patients either consented to participate in the Advarra IRB-approved study (in the case of the single-day TMS patients described in this work), or else were subject to an IRB Exempt Determination from Advarra IRB (in the case of the 36-day TMS patients) for the retrospective analysis of their anonymized data.\u003c/p\u003e","formattedTitle":"\u003cp\u003e\u003cstrong\u003eSingle-Day versus Once-Daily Transcranial Magnetic Stimulation in Depression: A Propensity-Matched Comparison of Treatment Outcomes\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[{"identity":"c88babf7-8120-4f7f-ad48-b99305fcd9a6","identifier":"10.13039/100016416","name":"Veterans Affairs Council, R.O.C.","awardNumber":"IK2 CX002603, I50 RX002864","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of Toronto","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"TMS, accelerated, depression, anxiety, D-cycloserine, augmentation, neuroplasticity, retrospective, propensity-matching, exponential-decay function","lastPublishedDoi":"10.21203/rs.3.rs-8476115/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8476115/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRecently, accelerated, pharmacologically augmented regimens for transcranial magnetic stimulation (TMS) have been described, allowing treatment completion in a single day. \u0026nbsp;However, comparisons of outcomes versus once-daily treatment regimens are lacking. \u0026nbsp;Here, we performed a propensity-matched retrospective analysis of individual patient data from a naturalistic sample of patients with major depression who received either a 36-day course of once-daily TMS or single-day of pharmacologically augmented TMS, at a large community practice. \u0026nbsp;Following exclusions, the initial set of 879 patient records yielded a preliminary sample of 114 individuals who received one-day TMS and 330 individuals who underwent 36-day TMS. \u0026nbsp;Propensity-score matching yielded a final analytic sample of N=191 36-day TMS patients, matched to N=106 one-day TMS patients. \u0026nbsp;Remission (PHQ9\u0026lt;5) was defined as the primary outcome measure, with response (≥50% PHQ9 improvement from baseline) as the secondary outcome measure; similar analyses were performed for anxiety symptoms using the GAD7. \u0026nbsp;PHQ9 remission was achieved in 49.1% (52/106) of the single-day TMS patients, versus 25.1% (48/191) of the 36-day patients (χ²=17.473, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.0001). \u0026nbsp;PHQ9 response was achieved in 71.7% (76/106) of the single-day TMS patients, versus 56.0% (107/191) of the 36-day patients (χ²=7.084, \u003cem\u003ep\u003c/em\u003e=0.0078). \u0026nbsp;Regarding anxiety symptoms, remission (GAD7\u0026lt;5) was achieved in 62.3% (66/106) of the single-day TMS patients, versus 33.0% (63/191) of the 36-day patients(χ²=23.79, p\u0026lt;0.0001). \u0026nbsp;Response was achieved in 72.6% (77/106) of the single-day versus 51.9% (98/189) of the 36-day TMS patients (χ²=12.16, \u003cem\u003ep\u003c/em\u003e=0.0005). \u0026nbsp;As previously observed, single-day TMS improvements were not immediate, but instead developed in a delayed fashion over the 6 weeks following treatment, and reaching a plateau at 6-12 weeks post-treatment. This pattern was well-modeled with an exponential-decay function, which yielded superior fits versus linear models in both groups, with the single-day TMS group showing a significantly greater magnitude of effect and rapidity of onset. Observed effects were robust across four slightly different versions of the single-day protocol, varying in target set (dorsolateral ± dorsomedial ± orbitofrontal stimulation), inter-session interval (20 versus 30 min), NMDA agonist (D-cycloserine versus D-serine), and presence/absence of lisdexamfetamine augmentation. Randomized controlled studies will be required for definitive comparisons of single-day to once-daily TMS and for optimization of the regimen. However, the present study suggests that single-day TMS regimens may be capable of achieving outcomes that are not only non-inferior, but indeed superior, to typical 36-day TMS regimens, when delivered under naturalistic conditions in the community.\u003c/p\u003e","manuscriptTitle":"Single-Day versus Once-Daily Transcranial Magnetic Stimulation in Depression: A Propensity-Matched Comparison of Treatment Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-07 05:13:32","doi":"10.21203/rs.3.rs-8476115/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"97f412fe-3c3d-410f-b96c-9e0cc2dff33f","owner":[],"postedDate":"January 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60353383,"name":"Psychiatry"}],"tags":[],"updatedAt":"2026-01-07T05:13:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-07 05:13:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8476115","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8476115","identity":"rs-8476115","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}