{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:00:12Z","timestamp":1783947612217,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"\n CYP2C19 metabolizes various selective serotonin reuptake inhibitors (SSRIs) and genetic\n CYP2C19<\/jats:italic>\n variants are associated with SSRI tolerability and response. Yet, whether CYP2C19 variability also impacts citalopram response remained unclear. We here evaluated associations between\n CYP2C19<\/jats:italic>\n genotypes and citalopram prescription data of 11,079 patients from the UK Biobank. Importantly, CYP2C19 ultrarapid metabolizers (UMs) were more likely to experience therapeutic failure (OR 2.03,\n P<\/jats:italic>\n \u2009=\u20090.002) and both CYP2C19 poor metabolizers (PMs) and UMs exhibited an increased likelihood of treatment resistance (PMs, OR 1.85,\n P<\/jats:italic>\n \u2009=\u20090.06; UMs, OR 1.74,\n P<\/jats:italic>\n \u2009=\u20090.05). Furthermore, inferred CYP2C19 metabolizer status showed significant monotonic trends with citalopram maintenance dose (from 19.7\u2009mg\/d in PMs to 24.4\u2009mg\/d in UMs; Jonckheere\u2013Terpstra\n P<\/jats:italic>\n \u2009=\u20090.017) and time to dose escalation (2.5\u2009years in PMs to 1.7\u2009years in UMs;\n P<\/jats:italic>\n \u2009=\u20090.006). Besides\n CYP2C19<\/jats:italic>\n , rare variant analyses identified\n BMP2K<\/jats:italic>\n as a novel candidate locus for SSRI response.\n BMP2K<\/jats:italic>\n variants were significantly associated with therapeutic failure in citalopram patients (\n P<\/jats:italic>\n \u2009=\u20095.49\u2009\u00d7\u200910\n \u22126<\/jats:sup>\n ) and this association was replicated in 220 escitalopram users (\n P<\/jats:italic>\n \u2009=\u20090.042). Furthermore, higher\n BMP2K<\/jats:italic>\n variant burden significantly correlated with lower maintenance dose. These findings provide the first report of a U\u2010shaped association between CYP2C19 metabolizer status and citalopram therapeutic outcomes and pinpoint\n BMP2K<\/jats:italic>\n as a novel candidate gene with potential contribution to interindividual differences in citalopram response. Collectively, these results demonstrate that\n CYP2C19<\/jats:italic>\n genotype is significantly associated with citalopram outcomes in a real\u2010world setting in which patient treatment was not guided by pharmacogenetics, thus avoiding open\u2010label awareness, eliminating expectation bias of genetic testing and highlighting the value of large\u2010scale biobank data for advancing precision psychiatry.\n <\/jats:p>","DOI":"10.1002\/cpt.70285","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T12:05:43Z","timestamp":1776168343000},"page":"412-419","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["\n CYP2C19<\/i>\n <\/scp>\n Genotype is Associated with Citalopram Treatment Outcomes in a Real\u2010World Setting"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-938X","authenticated-orcid":false,"given":"Yoomi","family":"Park","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology and Center for Molecular Medicine Karolinska Institutet and University Hospital Stockholm Sweden"},{"name":"Medical Research Center Seoul National University College of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-5444","authenticated-orcid":false,"given":"Yitian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Center for Molecular Medicine Karolinska Institutet and University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-6204","authenticated-orcid":false,"given":"Volker M.","family":"Lauschke","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology and Center for Molecular Medicine Karolinska Institutet and University Hospital Stockholm Sweden"},{"name":"Dr Margarete Fischer\u2010Bosch Institute of Clinical Pharmacology Stuttgart Germany"},{"name":"University of T\u00fcbingen T\u00fcbingen Germany"},{"name":"Department of Pharmacy, the Second Xiangya Hospital Central South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32802-7"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.12.013"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2020.4564"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1978"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-025-01894-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-022-00267-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0162-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0554-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.17050550"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3707"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e328340bc5a"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12320"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16091277"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-024-00794-y"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01062-9"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_2_10_17_1","first-page":"184","article-title":"Drug response Pharmacogenetics for 200,000 UK biobank participants","volume":"26","author":"McInnes G.","year":"2021","journal-title":"Pac. Symp. Biocomput."},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.029"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-025-00977-1"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01841-4"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab088"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-04026-y"}],"container-title":["Clinical Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70285","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70285","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T03:16:27Z","timestamp":1783912587000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cpt.70285"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70285","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]},"assertion":[{"value":"2025-11-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}