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Vetenskaps- och Vitterhets-Samh\u00e4llet"},{"DOI":"10.13039\/501100001729","name":"Stiftelsen f\u00f6r\u00a0Strategisk Forskning","doi-asserted-by":"publisher","award":["KF10-0039"],"award-info":[{"award-number":["KF10-0039"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018-02653"],"award-info":[{"award-number":["2018-02653"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001388","name":"Wenner-Gren Foundation","doi-asserted-by":"publisher","award":["SSv2019-0008"],"award-info":[{"award-number":["SSv2019-0008"]}],"id":[{"id":"10.13039\/100001388","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacogenomics J"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene <jats:italic>CYP2C19<\/jats:italic> influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if <jats:italic>CYP2C19<\/jats:italic> polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into <jats:italic>CYP2C19<\/jats:italic> metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005\u20132017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of <jats:italic>CYP2C19<\/jats:italic> were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR]\u2009=\u20091.3, 95% CI\u2009=\u20091.04\u20131.62, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR\u2009=\u20091.46, 95% CI\u2009=\u20091.05\u20132.02, <jats:italic>p<\/jats:italic>\u2009=\u20090.024). In a large study of the impact of <jats:italic>CYP2C19<\/jats:italic> metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.<\/jats:p>","DOI":"10.1038\/s41397-022-00294-4","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T19:16:04Z","timestamp":1667589364000},"page":"28-35","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-2192","authenticated-orcid":false,"given":"Erik","family":"Joas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Jonsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2141-2816","authenticated-orcid":false,"given":"Alexander","family":"Viktorin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4609-3620","authenticated-orcid":false,"given":"Erik","family":"Smedler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"P\u00e5lsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1426-2816","authenticated-orcid":false,"given":"Guy M.","family":"Goodwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4496-6451","authenticated-orcid":false,"given":"Mikael","family":"Land\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"294_CR1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.jad.2014.11.058","volume":"174","author":"A Karanti","year":"2015","unstructured":"Karanti A, Bobeck C, Osterman M, Kardell M, Tidemalm D, Runeson B, et al. 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Employment began June 1st 2022 after this study was submitted to the journal. GMG reports personal fees from Servier, personal fees from Lundbeck, personal fees from Medscape, personal fees from P1Vital, personal fees from Compass pathways, personal fees from Johnson&Johnson\/Janssen, personal fees from Sage Therapeutics, personal fees from Novartis, outside the submitted work. ML reports grants from The Swedish Foundation for Strategic Research, grants from The Swedish Medical Research council, grants from The Swedish Federal Government under the LUA\/ALF agreement during the conduct of the study; personal fees from Lundbeck pharmaceuticals outside the submitted work. All other authors report nothing to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}