{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T20:40:23Z","timestamp":1781901623632,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Paroxetine is a selective serotonin reuptake inhibitor (SSRI), approved for treatment of major depressive disorder and anxiety disorders. Some SSRIs are known to prolong the QT interval; however, clinical evidence to establish a lack of association between paroxetine and corrected QT interval (QTc) prolongation is limited. Therefore, this study aimed to characterize the relationship between paroxetine concentration and QT\/QTc interval following therapeutic doses in healthy individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This open\u2010label, single\u2010arm, dose\u2010escalating concentration\u2010QT study (NCT06065735) was performed in healthy adults (18\u201365\u2009years) without a history of cardiac disease or pre\u2010diagnosed mood disorder. Eligible individuals (n\u2009=\u200938) received paroxetine 20\u2009to 60\u2009mg QD for 1\u00a0week per dose level. Paroxetine plasma concentrations and electrocardiogram recordings were monitored over a 12\u2009h period on Days 1 (baseline), 7 (20\u2009mg), 14 (40\u2009mg) and 21 (60\u2009mg).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mean change from baseline in QTcF (\u0394QTcF) fluctuated between \u22127.1 and +4.7\u00a0ms. However, diurnal variation was also observed without treatment. A linear regression model showed no clinically significant effect of paroxetine concentrations on \u0394QTcF, with a weak slope of 0.0108\u2009ms\/ng\/mL (90% CI: 0.01, 0.03) and maximum \u0394QTcF of +0.42\u2009ms (90% CI: \u22122.68, 3.52) at 60\u2009mg QD, corresponding to a Cmax of 221.4 (95%CI: 179.6\u2013272.8) ng\/mL. Similarly, paroxetine did not affect the mean change in PR or QRS interval, or heart rate relative to baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Paroxetine does not prolong QTc interval in healthy individuals to any clinically meaningful extent at therapeutically relevant doses. This study supports the favourable cardiac safety profile of paroxetine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70398","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T03:58:48Z","timestamp":1768449528000},"page":"1385-1396","source":"Crossref","is-referenced-by-count":1,"title":["An open\u2010label, single\u2010arm, dose\u2010escalating concentration\u2013QT study to investigate the cardiac effects and safety of paroxetine in healthy adults"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2799-7643","authenticated-orcid":false,"given":"Sven C.","family":"van Dijkman","sequence":"first","affiliation":[{"name":"GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"F\u00e9lices","sequence":"additional","affiliation":[{"name":"PhinC Development  Massy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar","family":"Pandurangavittal","sequence":"additional","affiliation":[{"name":"ICON plc  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanman","family":"Ghorpade","sequence":"additional","affiliation":[{"name":"GSK  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Easterbrook","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Zabielski","sequence":"additional","affiliation":[{"name":"GSK  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-1430","authenticated-orcid":false,"given":"Oscar","family":"Della Pasqua","sequence":"additional","affiliation":[{"name":"GSK  London UK"},{"name":"Clinical Pharmacology &amp; Therapeutics Group UCL  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_11_2_1","article-title":"Paroxetine versus other anti\u2010depressive agents for depression Cochrane","author":"Purgato M","year":"2014","journal-title":"Database Syst Rev"},{"key":"e_1_2_11_3_1","unstructured":"US Food and Drug Administration.Highlights of prescribing information: PAXIL (paroxetine)(2021). 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