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We aimed to assess the association of exposure to venlafaxine, its active metabolite O-desmethylvenlafaxine (ODV) and its active moiety (i.e., venlafaxine + ODV) with treatment response and adverse effects in late-life depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We analyzed data from 325 participants from the Incomplete Response in Late-Life Depression: Getting to Remission (IRL-GRey) study. Participants were \u2265 60 years old, treated openly with venlafaxine (up to 300\u2005mg\/day) for 12 weeks. Treatment response was assessed with the Montgomery\u2013Asberg Depression Rating Scale and adverse effects were evaluated with the Udvalg for Kliniske Unders\u00f8gelser (UKU) rating scale. Venlafaxine-related exposures were derived from a published population pharmacokinetic model based on the IRL-GRey study, and their associations with treatment outcomes were assessed using regression analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      At week 4, the primary endpoint, higher venlafaxine-related exposures were not associated with greater symptom improvement. While at the end of treatment (week 12), we did not observe additional antidepressant benefit with increased venlafaxine-related exposures, higher ODV and active moiety exposures were associated with the occurrence of at least one adverse effect (odds ratio [OR] = 1.6 [1.1, 2.3],\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.02 and 1.8 [1.2, 2.6],\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.003, respectively). Also, higher venlafaxine and active moiety exposures were associated with nausea\/vomiting (OR = 1.1 [1.0, 1.2],\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.02 and 2.3 [1.3, 4.0],\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.006); while higher active moiety exposure was associated with orthostatic dizziness (OR = 1.9 [1.1, 3.2],\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.02).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest a potential threshold effect, where venlafaxine-related exposure past a certain level did not enhance antidepressant response but increased adverse-effect burden. These results support incorporating exposure measures from therapeutic drug monitoring in antidepressant studies to address the heterogeneity of safety and tolerability outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/07067437261451057","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:13:43Z","timestamp":1778750023000},"page":"691-702","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Venlafaxine Exposure And Treatment Outcomes In Older Adults With Depression: Association entre l\u2019exposition \u00e0 la venlafaxine et les r\u00e9sultats du traitement chez les personnes \u00e2g\u00e9es atteintes de d\u00e9pression"],"prefix":"10.1177","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1594-666X","authenticated-orcid":false,"given":"Xiaoyu","family":"Men","sequence":"first","affiliation":[{"name":"University of 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