{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:08:05Z","timestamp":1789175285629,"version":"build-2803163510"},"reference-count":39,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und\nForschung","doi-asserted-by":"crossref","award":["01 KG 0906"],"award-info":[{"award-number":["01 KG 0906"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Electrocardiographic changes indicating a significantly increased risk of\nadverse cardiac effects, such as heart-rate corrected QT interval\nprolongation, are rare during antidepressant treatment; however, systematic\nanalyses are lacking. Therefore, our study aimed at investigating the\nrelationship between heart-rate corrected QT interval changes and both\ndosage and serum levels of escitalopram and venlafaxine in a\nwell-characterized study sample.<\/jats:p>\n                  <jats:p>Two hundred seven depressed patients received escitalopram (10\u201320 mg\/d) for 4\nweeks. Non-responders were switched to high-dose venlafaxine (150\u2013375 mg\/d)\nfor an additional 4 weeks of treatment. Serum concentrations were measured\nweekly and electrocardiograms were recorded at baseline, day 28 and day 56.\nRisk factors for heart-rate corrected QT interval prolongation were included\nas covariates in the analysis.<\/jats:p>\n                  <jats:p>Escitalopram did not significantly affect heart-rate corrected QT intervals.\nSwitching to high-dose venlafaxine resulted in a significant increase of\nmean QT intervals from day 29 to day 56 (p=0.007), more pronounced in\nmen (interaction p=0.038). Heart-rate corrected QT interval\nprolongation occurred in 5% of patients after escitalopram and 12% after\nvenlafaxine; notably, 12 patients experienced critical prolongations, all\nwith higher rates of known risk factors. No correlation between serum\nconcentrations and heart-rate corrected QT intervals were observed.<\/jats:p>\n                  <jats:p>Our findings indicate that escitalopram does not affect heart-rate corrected\nQT intervals, whereas venlafaxine is associated with a modest but\nsignificant heart-rate corrected QT interval prolongation, particularly in\nmales. Although infrequent, critical prolongations highlight the need for\nindividualized risk assessment, especially in patients with risk factors.\nThe lack of correlation with serum concentrations suggests that\npharmacokinetic monitoring alone may not reliably predict cardiac risk. Our\nresults underscore the importance of electrocardiogram monitoring with\nattention to sex-specific and clinical risk profiles.<\/jats:p>","DOI":"10.1055\/a-2793-9711","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:34:07Z","timestamp":1772152447000},"page":"320-327","source":"Crossref","is-referenced-by-count":0,"title":["Heart Rate-Corrected QT Interval Dynamics Following Antidepressant\nSwitching from Escitalopram to High-Dose Venlafaxine: Cardiac Safety Insights\nfrom the Early Medication Change Cohort"],"prefix":"10.1055","volume":"59","clinical-trial-number":[{"clinical-trial-number":"nct00974155","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8818-0138","authenticated-orcid":false,"given":"Jan","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"},{"name":"Department of Psychiatry and Psychotherapy & Focus\nProgram Translational Neuroscience, Translational Psychiatry, University Medical\nCenter of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Solheid","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca P.","family":"Quesada Ocete","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Department of Cardiology\nII\/Electrophysiology, University Medical Center of the Johannes Gutenberg\nUniversity Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Herzog","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"},{"name":"Department of Psychiatry and Psychotherapy & Focus\nProgram Translational Neuroscience, Translational Psychiatry, University Medical\nCenter of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Dreim\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin M.","family":"Kachel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne B.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"},{"name":"Department of Psychiatry and Psychotherapy & Focus\nProgram Translational Neuroscience, Translational Psychiatry, University Medical\nCenter of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Tadic","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"},{"name":"Department of Psychiatry, Psychosomatics and\nPsychotherapy, Dr. Fontheim Mentale Gesundheit, Liebenburg,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter F.","family":"Braus","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Vitos Rheingau, Eltville,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hiemke","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Lieb","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University\nMedical Center of the Johannes Gutenberg University Mainz, Mainz,\nGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"issue":"10","key":"ref1","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1056\/NEJMra032426","article-title":"Drug-induced prolongation of the QT interval","volume":"350","author":"D M Roden","year":"2004","journal-title":"N Engl J Med"},{"issue":"19","key":"ref2","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1093\/eurheartj\/ehi312","article-title":"Non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death","volume":"26","author":"S M Straus","year":"2005","journal-title":"Eur Heart J"},{"issue":"41","key":"ref3","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1093\/eurheartj\/ehv316","article-title":"2015 ESC guidelines for the management of patients with ventricular arrhythmias\nand the prevention of sudden cardiac death: the task force for the Management of\nPatients with ventricular arrhythmias and the prevention of sudden cardiac death\nof the European Society of Cardiology (ESC). Endorsed by: Association for\nEuropean Paediatric and Congenital Cardiology (AEPC)","volume":"36","author":"S G Priori","year":"2015","journal-title":"Eur Heart J"},{"issue":"03","key":"ref4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1176\/appi.ajp.2019.1760501","article-title":"QTc prolongation and psychotropic medications","volume":"177","author":"M C Funk","year":"2020","journal-title":"Am J Psychiatry"},{"key":"ref8","first-page":"687","article-title":"QTc prolongation by psychotropic drugs and the risk of Torsade de Pointes","volume":"108","author":"K Wenzel-Seifert","year":"2011","journal-title":"Dtsch Arztebl Int"},{"issue":"1\/02","key":"ref9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/s-0043-116492","article-title":"Consensus guidelines for therapeutic drug monitoring in psychiatry: update\n2017","volume":"51","author":"C Hiemke","year":"2018","journal-title":"Pharmacopsychiatry"},{"issue":"06","key":"ref10","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1177\/2042098618772979","article-title":"Evaluating the risk of QTc prolongation associated with antidepressant use in\nolder adults: a review of the evidence","volume":"9","author":"M P Rochester","year":"2018","journal-title":"Ther Adv Drug Saf"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"f288","DOI":"10.1136\/bmj.f288","article-title":"Qt interval and antidepressant use: a cross sectional study of electronic health\nrecords","volume":"346","author":"V M Castro","year":"2013","journal-title":"BMJ"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.euroneuro.2013.05.011","article-title":"The cardiovascular safety profile of escitalopram","volume":"23","author":"M E Thase","year":"2013","journal-title":"Eur Neuropsychopharmacol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.psym.2017.10.009","article-title":"Qtc prolongation, torsades de pointes, and psychotropic medications: a five year\nupdate","volume":"59","author":"S R Beach","year":"2018","journal-title":"Psychosomatics"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"727","DOI":"10.5114\/aoms.2019.86928","article-title":"Effects of antidepressants on QT interval in people with mental disorders","volume":"16","author":"W S Aranow","year":"2020","journal-title":"Arch Med Sci"},{"issue":"12","key":"ref16","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1177\/1060028014550645","article-title":"Risk of QT\/QTc prolongation among newer non-SSRI antidepressants","volume":"48","author":"N M Jasiak","year":"2014","journal-title":"Ann Pharmacother"},{"issue":"02","key":"ref17","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1365-2125.2007.02849.x","article-title":"Cardiovascular toxicity due to venlafaxine poisoning in adults: a review of 235\nconsecutive cases","volume":"64","author":"C Howell","year":"2007","journal-title":"Br J Clin Pharmacol"},{"issue":"03","key":"ref18","first-page":"343","article-title":"QTc interval prolongation and psychotropic drugs","volume":"8","author":"W V Vieweg","year":"2009","journal-title":"Expert Opin Drug Saf"},{"issue":"12","key":"ref19","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1177\/2045125317721662","article-title":"Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and\npharmacodynamic effects in their potentially additive nature","volume":"7","author":"A D Meid","year":"2017","journal-title":"Ther Adv Psychopharmacol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00228-017-2381-5","article-title":"Risk factors for QTc interval prolongation","volume":"74","author":"P C Heemskerk","year":"2018","journal-title":"Eur J Clin Pharmacol"},{"issue":"01","key":"ref21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11096-016-0414-2","article-title":"Risk factors for QTc prolongation: systematic review of the evidence","volume":"39","author":"E Vandael","year":"2017","journal-title":"Int J Clin Pharm"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1177\/1715163516641136","article-title":"Drug-induced QT. interval prolongation and torsades de pointes: Role of the\npharmacist in risk assessment, prevention and management","volume":"149","author":"J E Tisdale","year":"2016","journal-title":"Can Pharm J"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.euroneuro.2016.02.003","article-title":"Randomized controlled study of early medication change for non-improvers to\nantidepressant therapy in major depression--The EMC trial","volume":"26","author":"A Tadic","year":"2016","journal-title":"Eur Neuropsychopharmacol"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/JCP.0000000000001312","article-title":"Tolerability of high-dose venlafaxine after switch from escitalopram in\nnonresponding patients with major depressive disorder","volume":"41","author":"J Engelmann","year":"2021","journal-title":"J Clin Psychopharmacol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1542-474X.1997.tb00325.x","article-title":"An analysis of the time-relations of electrocardiograms","volume":"2","author":"H C Bazett","year":"1997","journal-title":"Anna Noninvasive 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Hefner","year":"2013","journal-title":"Int Rev Psychiatry"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jad.2019.02.060","article-title":"Association between citalopram, escitalopram and QTc prolongation in a\nreal-world geriatric setting","volume":"250","author":"G Crepeau-Gendron","year":"2019","journal-title":"J Affect Disord"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00406-016-0758-6","article-title":"Lack of relationship between plasma levels of escitalopram and QTc-interval\nlength","volume":"267","author":"M Carceller-Sindreu","year":"2017","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jad.2023.11.084","article-title":"Escitalopram-induced QTc prolongation and its relationship with KCNQ1, KCNE1,\nand KCNH2 gene polymorphisms","volume":"347","author":"Z Chen","year":"2024","journal-title":"J Affect Disord"},{"issue":"11","key":"ref32","doi-asserted-by":"crossref","first-page":"8311","DOI":"10.1007\/s00210-024-03190-9","article-title":"Exploring gender differences in pharmacokinetics of central nervous system\nrelated medicines based on a systematic review approach","volume":"397","author":"S M Lee","year":"2024","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"02","key":"ref33","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1124\/pharmrev.120.000206","article-title":"Sex- and Gender-Based Pharmacological Response to Drugs","volume":"73","author":"F Mauvais-Jarvis","year":"2021","journal-title":"Pharmacol Rev"},{"issue":"01","key":"ref34","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1248\/bpb.b212021","article-title":"Non-genomic action of sex steroid hormones in cardiac repolarization","volume":"36","author":"J Kurokawa","year":"2013","journal-title":"Biol Pharm Bull"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1055\/s-0044-102009","article-title":"QTc time correlates with amitriptyline and venlafaxine serum levels in elderly\npsychiatric inpatients","volume":"52","author":"G Hefner","year":"2019","journal-title":"Pharmacopsychiatry"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ajp.2015.06.001","article-title":"Venlafaxine induced QTc interval prolongation in a therapeutic dose","volume":"16","author":"A Bavle","year":"2015","journal-title":"Asian J Psychiatr"},{"issue":"04","key":"ref37","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/JCP.0000000000000336","article-title":"Increase of Heart Rate and QTc by Amitriptyline, But Not by Venlafaxine, Is\nCorrelated to Serum Concentration","volume":"35","author":"S Unterecker","year":"2015","journal-title":"J Clin Psychopharmacol"},{"issue":"06","key":"ref38","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/JCP.0000000000001287","article-title":"The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for\nDepression in Older Adults","volume":"40","author":"L M Behlke","year":"2020","journal-title":"J Clin Psychopharmacol"},{"issue":"02","key":"ref39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/FTD.0000000000001264","article-title":"How to Determine a Therapeutic Reference Range for a Psychotropic Drug\nSystematically? Recommendations of the TDM Task Force of the AGNP","volume":"47","author":"X M Hart","year":"2025","journal-title":"Ther Drug Monit"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11096-016-0414-2","article-title":"Risk factors for QTc-prolongation: systematic review of evidence","volume":"39","author":"E Vandeal","year":"2017","journal-title":"Int J Clin Pharm"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"972141","DOI":"10.3389\/fpsyt.2022.972141","article-title":"Systematic review and meta-analysis on the therapeutic reference range for\nescitalopram: Blood concentrations, clinical effects and serotonin transporter\noccupancy","volume":"13","author":"L Eichentopf","year":"2022","journal-title":"Front Psychiatry"},{"issue":"02","key":"ref42","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00213-023-06484-7","article-title":"Venlafaxine's therapeutic reference range in the treatment of depression\nrevised: a systematic review and meta-analysis","volume":"241","author":"X M Lense","year":"2024","journal-title":"Psychopharmacology (Berl)"},{"issue":"09","key":"ref43","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1177\/02698811211003477","article-title":"Antipsychotics in routine treatment are minor contributors to QT prolongation\ncompared to genetics and age","volume":"35","author":"L Hommers","year":"2021","journal-title":"J Psychopharmacol"}],"container-title":["Pharmacopsychiatry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2793-9711.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:29:00Z","timestamp":1789172940000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2793-9711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":39,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2026,9,11]]},"published-print":{"date-parts":[[2026,9]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2793-9711","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0176-3679","1439-0795"],"issn-type":[{"value":"0176-3679","type":"print"},{"value":"1439-0795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}