{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:09:56Z","timestamp":1784279396102,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":197,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z221100007422010"],"award-info":[{"award-number":["Z221100007422010"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Depression and Anxiety"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While antidepressant side effects are often expected to diminish with continued treatment, empirical evidence remains limited. This study investigates co\u2010trajectories of depressive severity with side\u2010effect burden (SEB) and associated factors in patients with major depressive disorder (MDD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed longitudinal data from 1377 MDD outpatients across three Chinese multicenter studies (2015\u20132022), with assessments at baseline, weeks 2, 4, 8, 12, and 24. Depression severity was measured using the Quick Inventory of Depressive Symptomatology\u2010Self Report (QIDS\u2010SR16). At the same time, SEB was quantified using the frequency, intensity, and burden of side effects rating (FIBSER). Dual\u2010trajectory modeling was used to identify distinct SEB and depression severity trajectories, with linear mixed\u2010effects models comparing depression changes across SEB groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four SEB trajectories were identified: no SEB (41.5%), early\u2010onset SEB (29.1%), late\u2010onset SEB (14.7%), and persistent SEB (13.9%). Depressive severity followed three trajectories: mild\u2010responsive (66.6%), moderate\u2010progressive (18.7%), and chronic\u2010severe (14.7%). Persistent SEB was associated with higher baseline depression severity (OR\u2009=\u20091.13, 95% CI: 1.08\u20131.17), antidepressant combination (OR\u2009=\u20093.7, 95% CI: 1.52\u2013 9.02), and poorer treatment outcomes. 7.3% exhibited concurrent chronic\u2010severe depressive severity and persistent SEB. Female (OR\u2009=\u20091.95, 95% CI: 1.11\u20133.42), younger age (OR\u2009=\u20095.02, 95% CI: 2.63\u20139.55), higher education (high school: OR\u2009=\u20092.5, 95% CI: 1.12\u20135.36; bachelor and above: OR\u2009=\u20092.68, 95% CI: 1.24\u20135.82), and combination antidepressant (OR\u2009=\u20098.27, 95% CI: 2.69\u201325.45) were significant risk factors for concurrent severe symptoms and persistent SEB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Persistent antidepressant side effects coevolve with unfavorable depression trajectories over 6 months. Clinicians should prioritize early monitoring and tailored interventions for high\u2010risk subgroups, particularly those with severe baseline symptoms or on combination therapy. These findings underscore the importance of continuous monitoring and personalized interventions to manage antidepressant side effects effectively.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/da\/9897990","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T08:58:01Z","timestamp":1784278681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identifying Clinical Predictors of Unfavorable Treatment Trajectories in Major Depressive Disorder: A National Multicentered Prospective Cohort Longitudinal, Naturalistic Study"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-2810","authenticated-orcid":false,"given":"Xuequan","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0902-2658","authenticated-orcid":false,"given":"Kaiyan","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4139-3048","authenticated-orcid":false,"given":"Xu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7810-5070","authenticated-orcid":false,"given":"Lei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7849-5592","authenticated-orcid":false,"given":"Yuan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9713-1458","authenticated-orcid":false,"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-1188","authenticated-orcid":false,"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32802-7"},{"key":"e_1_2_11_2_2","unstructured":"American Psychiatric Association Practice Guideline for the Treatment of Patients With Major Depressive Disorder (Revision) American Journal of Psychiatry 2000 157 no. 4 Suppl 1\u201345."},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(03)00112-0"},{"key":"e_1_2_11_4_2","first-page":"10","article-title":"Treatment Recommendations versus Treatment Realities: Recognizing the Rift and Understanding the Consequences","volume":"62","author":"Frank E.","year":"2001","journal-title":"The Journal of Clinical Psychiatry"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0447.2002.1r084.x"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.05.001"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01533-1"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/acps.13764"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2013.05.007"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200825060-00004"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2009.00699.x"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjmed-2021-000017"},{"key":"e_1_2_11_13_2","article-title":"Pharmacologic Treatment of Dimensional Anxious Depression: A Review","volume":"16","author":"Ionescu D. 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