{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:57:29Z","timestamp":1791979049597,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007371","name":"Svend Andersen Fonden","doi-asserted-by":"publisher","award":["03\u201010\u20102022"],"award-info":[{"award-number":["03\u201010\u20102022"]}],"id":[{"id":"10.13039\/501100007371","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Robust evidence associates immunoinflammatory dysfunction and bipolar disorder (BD), with immune dysregulation present in patients newly diagnosed with BD. This suggests that anti\u2010inflammatory agents, like low\u2010dose aspirin (LDA), might be repurposed in the treatment of early\u2010stage BD. Building on pharmacoepidemiologic and meta\u2010analytic evidence, we conducted the first randomised controlled trial (RCT) testing the effects of add\u2010on LDA in patients with newly diagnosed BD. We hypothesised that add\u2010on treatment with LDA would reduce mood instability (MI), activity instability (AI), and depression severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this parallel group, triple\u2010blind, superiority RCT, patients newly diagnosed with BD, recruited from a public outpatient mood disorder clinic in the Capital Region of Denmark, were randomised 1:1 to 150\u2009mg acetylsalicylic acid or placebo by an independent third party. The primary outcome was average MI at 6\u2010month follow\u2010up, assessed by the Root Mean Square of Successive Differences (RMSSDs) method. Secondary outcomes included average AI, assessed by the RMSSD method, and change in depressive symptoms, assessed with the 6\u2010item Hamilton Depression Rating Scale, at 6 months. Tertiary outcomes included sleep variability, cognition, manic symptoms and questionnaires at 6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two hundred fifty patients were randomised from January 20, 2022, to May 30, 2024, with the last follow\u2010up on November 18, 2024. Analyses included data from 240 patients (120 received placebo; 120 LDA), with a mean of 108 (SD\u2009=\u200957) daily mood registrations. The estimated treatment difference for MI was 0.022 (95% CI: \u22120.056 to 0.1,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.58) for LDA compared to placebo, indicating no clinically relevant difference. No beneficial effects of LDA were found across secondary or tertiary outcomes. Methodologically, randomisation and blinding were successful, and serum\u2010thromboxane B2 levels confirmed high adherence to LDA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Low\u2010dose aspirin did not demonstrate any benefit on MI or on secondary or tertiary outcomes in patients with newly diagnosed BD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Registration<\/jats:title>\n                    <jats:p>Clinicaltrials.gov registration number: NCT05035316<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acps.70055","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T12:32:46Z","timestamp":1764505966000},"page":"214-224","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["No Effect of Low\u2010Dose Aspirin Versus Placebo as Add\u2010On Treatment in Bipolar Disorder\u2014Results From a Randomised Controlled Trial (the A\u2010Bipolar\n                    <scp>RCT<\/scp>\n                    )"],"prefix":"10.1111","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-358X","authenticated-orcid":false,"given":"Caroline Fussing","family":"Bruun","sequence":"first","affiliation":[{"name":"Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen Copenhagen University Hospital \u2010 Mental Health Services CPH  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences 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