DART: A Daily Monitoring Framework for Distinguishing Withdrawal from Relapse During Antipsychotic Tapering

DART: A Daily Monitoring Framework for Distinguishing Withdrawal from Relapse During Antipsychotic Tapering | 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 Case Report DART: A Daily Monitoring Framework for Distinguishing Withdrawal from Relapse During Antipsychotic Tapering Steven Richter, Susan B Carol This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8935281/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract Background When symptoms re-emerge during antipsychotic dose reduction, standard practice typically interprets this as relapse and responds with dose reinstatement. This assumption is rarely testable: a single-timepoint assessment cannot distinguish genuine relapse from withdrawal—a time-limited response that resolves without intervention—or from unmasking of iatrogenic receptor upregulation, whether as the primary driver or superimposed on underlying illness (dopamine supersensitivity psychosis, DSP). These possibilities require fundamentally different responses, and misidentification carries consequences: dose reinstatement for unmasked supersensitivity treats the immediate presentation while potentially deepening the receptor changes driving it. The frequency of this misclassification is uncertain but may be clinically significant: when Fallon and colleagues ( 2012 ) systematically assessed treatment-compliant patients experiencing relapse, 39% met criteria for supersensitivity psychosis. Tapering methodologies and frameworks for identifying discontinuation syndromes exist and have shown promise—but their appropriate use depends on trajectory characterization that current practice cannot provide. A systematic review identified only five antipsychotic discontinuation studies with daily clinical assessment—the frequency necessary to detect short-lasting withdrawal symptoms. No published protocol links observed symptom trajectories to tapering decisions through daily monitoring. Methods From trajectory patterns observed during daily monitoring of occupancy-guided antipsychotic tapering, we derived DART (Daily Adaptive Response Tapering), a decision framework linking tapering progression to observed recovery trajectories. Results Daily monitoring detected withdrawal features invisible to standard assessment intervals: repeated oscillations between apparent recovery (0–1/10) and symptom re-emergence (10/10) extending 53 days, with a tertiary elevation at days 32–39 that resolved without intervention but would register as "relapse" at any single assessment timepoint. Withdrawal dyskinesia covaried temporally with psychotic symptoms, suggesting a common dopaminergic mechanism. Peak severity reached 10/10 during each of eight sequential reductions before amplitude narrowing emerged after months—consistent with receptor normalization timescales but detectable only through sustained daily monitoring. These features informed DART's core elements: confirmation holds, step-size calibration based on prior response, and trajectory-based criteria for distinguishing withdrawal from relapse. Conclusions Daily monitoring revealed withdrawal trajectory complexity that could be misclassified as relapse under standard assessment intervals. DART proposes a transferable, low-resource framework applicable across populations where standard assessment tools are less reliable, including those at elevated risk for supersensitivity. Whether multiphasic withdrawal patterns generalize, and whether DART could improve withdrawal-relapse distinction in practice and research, requires prospective evaluation. Psychiatry Clinical Pharmacology antipsychotic withdrawal antipsychotic discontinuation antipsychotic tapering DART protocol hyperbolic tapering receptor occupancy multiphasic withdrawal withdrawal dyskinesia relapse distinction dopamine supersensitivity psychosis daily monitoring Full Text Additional Declarations The authors declare no competing interests. Supplementary Files 1DARTAdaptiveResponseTaperingB.docx SupplementalMaterialsAG.pdf Cite Share Download PDF Status: Posted Version 3 posted You are reading this latest preprint version Show more versions 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-8935281","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":600228256,"identity":"e7d7ad7d-ce77-443b-a74b-b08c3dc8fe0d","order_by":0,"name":"Steven 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hyperbolic tapering, receptor occupancy, multiphasic withdrawal, withdrawal dyskinesia, relapse distinction, dopamine supersensitivity psychosis, daily monitoring","lastPublishedDoi":"10.21203/rs.3.rs-8935281/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8935281/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWhen symptoms re-emerge during antipsychotic dose reduction, standard practice typically interprets this as relapse and responds with dose reinstatement. This assumption is rarely testable: a single-timepoint assessment cannot distinguish genuine relapse from withdrawal\u0026mdash;a time-limited response that resolves without intervention\u0026mdash;or from unmasking of iatrogenic receptor upregulation, whether as the primary driver or superimposed on underlying illness (dopamine supersensitivity psychosis, DSP). These possibilities require fundamentally different responses, and misidentification carries consequences: dose reinstatement for unmasked supersensitivity treats the immediate presentation while potentially deepening the receptor changes driving it. The frequency of this misclassification is uncertain but may be clinically significant: when Fallon and colleagues (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2012\u003c/span\u003e) systematically assessed treatment-compliant patients experiencing relapse, 39% met criteria for supersensitivity psychosis. Tapering methodologies and frameworks for identifying discontinuation syndromes exist and have shown promise\u0026mdash;but their appropriate use depends on trajectory characterization that current practice cannot provide. A systematic review identified only five antipsychotic discontinuation studies with daily clinical assessment\u0026mdash;the frequency necessary to detect short-lasting withdrawal symptoms. No published protocol links observed symptom trajectories to tapering decisions through daily monitoring.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFrom trajectory patterns observed during daily monitoring of occupancy-guided antipsychotic tapering, we derived DART (Daily Adaptive Response Tapering), a decision framework linking tapering progression to observed recovery trajectories.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDaily monitoring detected withdrawal features invisible to standard assessment intervals: repeated oscillations between apparent recovery (0\u0026ndash;1/10) and symptom re-emergence (10/10) extending 53 days, with a tertiary elevation at days 32\u0026ndash;39 that resolved without intervention but would register as \"relapse\" at any single assessment timepoint. Withdrawal dyskinesia covaried temporally with psychotic symptoms, suggesting a common dopaminergic mechanism. Peak severity reached 10/10 during each of eight sequential reductions before amplitude narrowing emerged after months\u0026mdash;consistent with receptor normalization timescales but detectable only through sustained daily monitoring. These features informed DART's core elements: confirmation holds, step-size calibration based on prior response, and trajectory-based criteria for distinguishing withdrawal from relapse.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eDaily monitoring revealed withdrawal trajectory complexity that could be misclassified as relapse under standard assessment intervals. DART proposes a transferable, low-resource framework applicable across populations where standard assessment tools are less reliable, including those at elevated risk for supersensitivity. Whether multiphasic withdrawal patterns generalize, and whether DART could improve withdrawal-relapse distinction in practice and research, requires prospective evaluation.\u003c/p\u003e","manuscriptTitle":"DART: A Daily Monitoring Framework for Distinguishing Withdrawal from Relapse During Antipsychotic Tapering","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2026-03-11 19:22:03","doi":"10.21203/rs.3.rs-8935281/v3","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}},{"code":2,"date":"2026-03-03 22:00:32","doi":"10.21203/rs.3.rs-8935281/v2","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}},{"code":1,"date":"2026-02-25 17:12:06","doi":"10.21203/rs.3.rs-8935281/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":"43df91dd-e560-4f0d-8df2-a8066bc65ddd","owner":[],"postedDate":"March 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":63872285,"name":"Psychiatry"},{"id":63872286,"name":"Clinical Pharmacology"}],"tags":[],"updatedAt":"2026-02-25T17:12:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-11 19:22:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v3","identity":"rs-8935281","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8935281","identity":"rs-8935281","version":["v3"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}