{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T22:39:39Z","timestamp":1784932779906,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2009906"],"award-info":[{"award-number":["2022YFC2009906"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2009900"],"award-info":[{"award-number":["2022YFC2009900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose\u2013response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose\u2013response meta\u2010analyses to fill this gap.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose\u2013response relationship was evaluated using a one\u2010stage random\u2010effects dose\u2013response meta\u2010analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The dose\u2013response meta\u2010analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37\u2009mg\/day, and the near\u2010maximal effective dose (95% effective dose) was 17.93\u2009mg\/day. Visual inspection of the dose\u2010efficacy curve suggests that a plateau possibly had not been reached yet at 20\u2009mg\/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13709","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T08:28:40Z","timestamp":1719995320000},"page":"536-545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Vortioxetine for depression in adults: A systematic review and dose\u2013response meta\u2010analysis of randomized controlled trials"],"prefix":"10.1111","volume":"78","author":[{"given":"Xin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Mental Health Center West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Mental Health Center West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-8257","authenticated-orcid":false,"given":"Wenqi","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Mental Health Center West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Division of Neurology and Psychiatry West China Xiamen Hospital of Sichuan University  Xiamen China"},{"name":"Department of Radiology, Huaxi MR Research Center (HMRRC) West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Geriatric Psychiatry The Fourth People's Hospital of Chengdu  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Ziyang Psychosis Hospital  Ziyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurou","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Mental Health Center West China Hospital of Sichuan University  Chengdu China"},{"name":"Department of Geriatric Psychiatry The Fourth People's Hospital of Chengdu  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Mental Health Center West China Hospital of Sichuan University  Chengdu China"},{"name":"Department of Geriatric Chengdu Second People's Hospital  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Mental Health Center West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7254-0557","authenticated-orcid":false,"given":"Weihong","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Mental Health Center West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"World Health Organization.International Classification of Diseases 11th Revision. 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