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We included CRC cases and controls, matched (1:10) on age, sex, and index date (i.e., CRC diagnosis date\/matched date). Antidepressant exposures were ascertained by duration (i.e., varying windows from 15 to 1\u2009year before CRC diagnosis), drug classes (tricyclic antidepressants (TCAs), selective serotonin reuptake inhibiters (SSRIs), other), cumulative dose and treatment intensity. We used multivariable conditional logistic regression models and interpreted odds ratios as relative risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 10,171 CRC cases (688 EAO\u2010CRC; 9483 AAO\u2010CRC) and 90\u2009928 controls, antidepressants exposure in the 15\u2010year window was associated with a lower risk of CRC overall (adjusted relative risk [aRR] 0.84; 95% CI 0.80, 0.89), EAO\u2010CRC (aRR 0.54; 95% CI 0.44, 0.66), and AAO\u2010CRC (aRR 0.87; 95% CI 0.83, 0.92). Across narrowing exposure windows, associations persisted up to 7\u2009years before CRC diagnosis, then weakened. Inverse associations were also observed for TCAs (aRR 0.83; 95% CI 0.77, 0.89) and SSRIs (aRR 0.86; 95% CI 0.81, 0.91) and CRC. Cumulative dose and treatment intensity showed no associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Across all age groups, antidepressant exposure in the earlier exposure windows (15\u20137\u2009years) was associated with a lower CRC risk, with the strongest effect at the 15\u2010year window.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pds.70316","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:30:02Z","timestamp":1767166202000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population\u2010Based Case\u2013Control Study of Antidepressants in Early and Average\u2010Age Onset Colorectal Cancer: The Impact of Exposure Window, Class, Dose, and Intensity"],"prefix":"10.1002","volume":"35","author":[{"given":"Vicki","family":"Cheng","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver British Columbia Canada"},{"name":"Collaboration for Outcomes Research and Evaluation  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Sayre","sequence":"additional","affiliation":[{"name":"British Columbia Centre on Substance Use  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vienna","family":"Cheng","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver British Columbia Canada"},{"name":"Collaboration for Outcomes Research and Evaluation  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Loree","sequence":"additional","affiliation":[{"name":"Cancer Control Research BC Cancer  Vancouver British Columbia Canada"},{"name":"Faculty of Medicine, Division of Medical Oncology University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharlene","family":"Gill","sequence":"additional","affiliation":[{"name":"Cancer Control Research BC Cancer  Vancouver British Columbia Canada"},{"name":"Faculty of Medicine, Division of Medical Oncology University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Cancer Control Research BC Cancer  Vancouver British Columbia Canada"},{"name":"School of Population and Public Health University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A.","family":"De Vera","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences University of British Columbia  Vancouver British Columbia Canada"},{"name":"Collaboration for Outcomes Research and Evaluation  Vancouver British Columbia Canada"},{"name":"Centre for Health Evaluation and Outcome Sciences University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ps.201300371"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/070674371506001207"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011006.pub4"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011006.pub3"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2012.06.001"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD014682.pub2"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.02.064"},{"issue":"6","key":"e_1_2_13_9_1","first-page":"1207","article-title":"Influence of Histamine and Serotonin Antagonists on the Growth of Xenografted Human Colorectal Tumors","volume":"67","author":"Barkla D. 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