{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:49:55Z","timestamp":1792046995935,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"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"],"abstract":"<jats:p>\n                    Escitalopram is a frequently prescribed antidepressant drug.\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotype is a major determinant of escitalopram metabolism and treatment outcome. However, real\u2010life studies show a high degree of genotype\u2013phenotype mismatch in escitalopram metabolism. The present study aimed to identify comedication with proton pump inhibitors (PPIs) and quantify phenoconversion of escitalopram metabolism in\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    \u2010genotyped patients by reprocessing high\u2010resolution mass spectra from therapeutic drug monitoring (TDM) analyses. Patients were included from a combined TDM\/pharmacogenetics (PGx) laboratory facility in Oslo, Norway. TDM profiles of escitalopram and\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotypes were available in the laboratory database. Reprocessing of high\u2010resolution mass spectra by exact mass and fragment detection identified possible comedication with pantoprazole, esomeprazole\/omeprazole or lansoprazole using mzCloud reference library. Patients were grouped as normal metabolizers (NMs), intermediate metabolizers (IMs), poor metabolizers (PMs), rapid metabolizers (RM), or ultrarapid metabolizers (UM). Primary outcome measure was\n                    <jats:italic>N<\/jats:italic>\n                    \u2010desmethylescitalopram\u2010to\u2010escitalopram metabolic ratio (MR; CYP2C19 biomarker) in UMs vs. PMs. 2818 patients were included, constituting 2373 without and 445 (15.8%) with PPIs. Most patients were females (64.2%). Regarding CYP2C19 phenotype distribution, the cohort comprised 39.3% NMs, 29.3% IMs, 2.6% PMs, 24.6% RMs, and 4.2% UMs. Escitalopram MR was 4.5\u2010fold higher in CYP2C19 UMs vs. PMs without PPIs (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), while this difference was 2.8\u2010fold in pantoprazole users (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), and 1.8\u2010fold in esomeprazole\/omeprazole users (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.2). In conclusion, PPIs show significant phenoconversion of CYP2C19\u2010mediated escitalopram metabolism with esomeprazole\/omeprazole exhibiting a stronger effect than pantoprazole. The novel method for identification of interacting comedications in TDM samples illustrates the innovative potential of high\u2010resolution mass spectrometry in precision medicine.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70506","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:33:13Z","timestamp":1792045993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reprocessing Mass Spectra from Therapeutic Drug Monitoring to Unveil Proton Pump Inhibitor Use and Quantify Phenoconversion of Escitalopram Metabolism in\n                    <scp>CYP2C19<\/scp>\n                    \u2010Genotyped Patients"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7300-5329","authenticated-orcid":false,"given":"Kristine","family":"Hole","sequence":"first","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7261-275X","authenticated-orcid":false,"given":"Birgit M.","family":"Wollmann","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-7753","authenticated-orcid":false,"given":"Julia Carolin","family":"Stingl","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-2751","authenticated-orcid":false,"given":"Espen","family":"Molden","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"},{"name":"Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"Drug Usage Statistics<https:\/\/clincalc.com\/drugstats\/Drugs\/Escitalopram>. Accessed March 24 2026."},{"key":"e_1_2_9_2_1","article-title":"Escitalopram versus other antidepressive agents for depression","volume":"2016","author":"Cipriani A.","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1186\/s12888-023-05382-8","article-title":"Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta\u2010analysis","volume":"23","author":"Yin J.","year":"2023","journal-title":"BMC Psychiatry"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1001\/jamapsychiatry.2019.4815","article-title":"Individual differences in response to antidepressants: a meta\u2010analysis of placebo\u2010controlled randomized clinical trials","volume":"77","author":"Maslej M.M.","year":"2020","journal-title":"JAMA Psychiatry"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1111\/bcp.16156","article-title":"Combined effect of CYP2C19 and CYP2D6 genotypes on escitalopram serum concentration and its metabolic ratio in a European patient population","volume":"90","author":"Faraj P.","year":"2024","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1176\/appi.ajp.2017.17050550","article-title":"Impact of CYP2C19 genotype on Escitalopram exposure and therapeutic failure: a retrospective study based on 2087 patients","volume":"175","author":"Juki\u0107 M.M.","year":"2018","journal-title":"Am. J. Psychiatry"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1002\/cpt.2526","article-title":"Clinical Pharmacogenetics implementation consortium guideline for CYP2C19 genotype and Clopidogrel therapy: 2022 update","volume":"112","author":"Lee C.R.","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","DOI":"10.3390\/jpm15070274","article-title":"Major allele frequencies in CYP2C9 and CYP2C19 in Asian and European populations: a case study to disaggregate data among large racial categories","volume":"15","author":"Nieh H.V.","year":"2025","journal-title":"J. Pers. Med."},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1097\/FTD.0000000000000991","article-title":"Identification of Escitalopram metabolic ratios as potential biomarkers for predicting CYP2C19 poor metabolizers","volume":"44","author":"Faraj P.","year":"2022","journal-title":"Ther. Drug Monit."},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.euroneuro.2018.05.009","article-title":"Effect of cytochrome CYP2C19 metabolizing activity on antidepressant response and side effects: meta\u2010analysis of data from genome\u2010wide association studies","volume":"28","author":"Fabbri C.","year":"2018","journal-title":"Eur. Neuropsychopharmacol."},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","DOI":"10.3390\/ph16091277","article-title":"The effects of CYP2C19 genotype on proxies of SSRI antidepressant response in the UK biobank","volume":"16","author":"Wong W.L.E.","year":"2023","journal-title":"Pharmaceuticals (Basel)"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/cpt.3378","article-title":"Phenoconversion due to drug\u2010drug interactions in CYP2C19 genotyped healthy volunteers","volume":"116","author":"Abouir K.","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","DOI":"10.1111\/cts.13887","article-title":"Inflammation altered correlation between CYP2C19 genotype and CYP2C19 activity in patients receiving voriconazole","volume":"17","author":"Klomp S.D.","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"e_1_2_9_14_1","article-title":"Proton pump inhibitors for the prevention of non\u2010steroidal anti\u2010inflammatory drug\u2010induced ulcers and dyspepsia","volume":"5","author":"Garegnani L.","year":"2025","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1016\/j.cgh.2024.01.047","article-title":"Prescribing of proton pump inhibitors for prevention of upper gastrointestinal bleeding in US outpatient visits","volume":"22","author":"Kurlander J.E.","year":"2024","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/j.1365-2125.2010.03717.x","article-title":"Influences of different proton pump inhibitors on the anti\u2010platelet function of clopidogrel in relation to CYP2C19 genotypes","volume":"70","author":"Furuta T.","year":"2010","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"18158","DOI":"10.1038\/s41598-025-02872-5","article-title":"Comparative in\u00a0vitro assessment of CYP2C19 inhibition by ilaprazole and conventional proton pump inhibitors using a high throughput fluorometric assay","volume":"15","author":"Priyadharshini A.","year":"2025","journal-title":"Sci. Rep."},{"key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/s-0043-116492","article-title":"Consensus guidelines for therapeutic drug monitoring in Neuropsychopharmacology: update 2017","volume":"51","author":"Hiemke C.","year":"2018","journal-title":"Pharmacopsychiatry"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1111\/bcp.16048","article-title":"Therapeutic drug monitoring, liquid biopsies or pharmacogenomics for prediction of human drug metabolism and response","volume":"91","author":"Ingelman\u2010Sundberg M.","year":"2025","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.tips.2022.09.011","article-title":"Pharmacogenomics in treatment of depression and psychosis: an update","volume":"43","author":"Jukic M.","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1055\/a-2039-2829","article-title":"Low Escitalopram concentrations in patients with depression predict treatment failure: a naturalistic retrospective study","volume":"56","author":"Hart X.M.","year":"2023","journal-title":"Pharmacopsychiatry"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"32470","DOI":"10.1038\/s41598-025-18517-6","article-title":"Effectiveness and safety of escitalopram treatment personalized based on therapeutic drug monitoring of drug plasma concentration: a prospective cohort study","volume":"15","author":"Vukovi\u0107 P.G.","year":"2025","journal-title":"Sci. Rep."},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","DOI":"10.1111\/nmo.70010","article-title":"The use of antidepressants in patients with depression is associated with gastroesophageal reflux disease and disease severity","volume":"37","author":"Saleh S.","year":"2025","journal-title":"Neurogastroenterol. Motil."},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.pnpbp.2021.110266","article-title":"Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: a systematic review and meta\u2010analysis","volume":"109","author":"Oliva V.","year":"2021","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27051680"},{"key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrgastro.2013.105","article-title":"Serotonin signalling in the gut\u2010\u2010functions, dysfunctions and therapeutic targets","volume":"10","author":"Mawe G.M.","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s00228-012-1252-3","article-title":"CYP2C19 polymorphism affects single\u2010dose pharmacokinetics of oral pantoprazole in healthy volunteers","volume":"68","author":"Gawro\u0144ska\u2010Szklarz B.","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1751-2980.2008.00363.x","article-title":"Blood concentration of pantoprazole sodium is significantly high in hepatogenic peptic ulcer patients, especially those with a poor CYP2C19 metabolism","volume":"10","author":"Shao J.G.","year":"2009","journal-title":"J. Dig. Dis."},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1124\/dmd.112.045575","article-title":"Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: focus on cytochrome P450 2C19","volume":"40","author":"Zvyaga T.","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2165\/00003088-200746040-00002","article-title":"The clinical pharmacokinetics of escitalopram","volume":"46","author":"Rao N.","year":"2007","journal-title":"Clin. Pharmacokinet."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70506","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70506","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70506","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:33:17Z","timestamp":1792045997000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":30,"alternative-id":["10.1002\/cpt.70506"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70506","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"assertion":[{"value":"2026-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70506"}}