{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:51:37Z","timestamp":1783075897114,"version":"3.54.6"},"reference-count":55,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Affective Disorders"],"published-print":{"date-parts":[[2018,2]]},"DOI":"10.1016\/j.jad.2017.11.046","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T13:15:24Z","timestamp":1510578924000},"page":"506-511","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"special_numbering":"C","title":["Antidepressant polypharmacy and the potential of pharmacokinetic interactions: Doxepin but not mirtazapine causes clinically relevant changes in venlafaxine metabolism"],"prefix":"10.1016","volume":"227","author":[{"given":"Michael","family":"Paulzen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Haen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hiemke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Fay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Unholzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Gr\u00fcnder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Schoretsanitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jad.2017.11.046_bib1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1527-3458.2001.tb00198.x","article-title":"A review of the pharmacological and clinical profile of mirtazapine","volume":"7","author":"Anttila","year":"2001","journal-title":"CNS Drug Rev."},{"key":"10.1016\/j.jad.2017.11.046_bib2","series-title":"Therapeutisches Drug Monitoring bei Antipsychotika: die Entwicklung der Analytik von Antipsychotika und ihre Relevanz bei der Therapieleitung schizophrener Patienten am Beispiel des Arzneistoffes Risperidon","author":"Bader","year":"2009"},{"key":"10.1016\/j.jad.2017.11.046_bib3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1055\/s-2005-862617","article-title":"Determination of five commonly used antipsychotics in human serum by high performance-liquid chromatography (HPLC) and electrochemical detection","volume":"38","author":"Bader","year":"2005","journal-title":"Pharmacopsychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s11920-012-0281-z","article-title":"Treatment of depression in older adults","volume":"14","author":"Bottino","year":"2012","journal-title":"Curr. Psychiatry Rep."},{"key":"10.1016\/j.jad.2017.11.046_bib5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/YCO.0b013e32831be9ef","article-title":"Augmentation strategies for treatment-resistant depression","volume":"22","author":"Carvalho","year":"2009","journal-title":"Curr. Opin. Psychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1177\/026988110201600413","article-title":"Venlafaxine: the relationship between dose, plasma concentration and clinical response in depressive patients","volume":"16","author":"Charlier","year":"2002","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib7","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S0893-133X(98)00113-4","article-title":"O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants","volume":"20","author":"Fogelman","year":"1999","journal-title":"Neuropsychopharmacol.: Off. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib8","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1097\/FTD.0b013e31828816e0","article-title":"Severe tremor after cotrimoxazole-induced elevation of venlafaxine serum concentrations in a patient with major depressive disorder","volume":"35","author":"Geber","year":"2013","journal-title":"Ther. Drug Monit."},{"key":"10.1016\/j.jad.2017.11.046_bib9","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.jad.2011.10.033","article-title":"Pharmacotherapeutic trends in 2231 psychiatric inpatients with bipolar depression from the international AMSP project between 1994 and 2009","volume":"136","author":"Greil","year":"2012","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.jad.2017.11.046_bib10","series-title":"Aufbau eines TDM-Labors zur Individualisierung der Psychopharmakotherapie von Patienten mit affektiven St\u00f6rungen","author":"Greiner","year":"2008"},{"key":"10.1016\/j.jad.2017.11.046_bib11","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1055\/s-0031-1286285","article-title":"Therapeutic drug monitoring in pharmacovigilance and pharmacotherapy safety","volume":"44","author":"Haen","year":"2011","journal-title":"Pharmacopsychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib12","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4088\/JCP.v62n0609","article-title":"Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study","volume":"62","author":"Hajak","year":"2001","journal-title":"J. Clin. Psychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib13","first-page":"47","article-title":"Doxepin's effects on chronic pain and depression: a controlled study","volume":"45","author":"Hameroff","year":"1984","journal-title":"J. Clin. Psychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib14","article-title":"Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017","author":"Hiemke","year":"2017","journal-title":"Pharmacopsychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib15","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1097\/JCP.0000000000000576","article-title":"Interaction between risperidone, venlafaxine, and metronidazole: an unknown thread","volume":"36","author":"Hovancakova","year":"2016","journal-title":"J. Clin. Psychopharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib16","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1007\/s00213-014-3825-6","article-title":"The influences of CYP2D6 genotypes and drug interactions on the pharmacokinetics of venlafaxine: exploring predictive biomarkers for treatment outcomes","volume":"232","author":"Jiang","year":"2015","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.jad.2017.11.046_bib17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/tpj.2014.50","article-title":"Influence of CYP2D6 and CYP2C19 genotypes on venlafaxine metabolic ratios and stereoselective metabolism in forensic autopsy cases","volume":"15","author":"Karlsson","year":"2015","journal-title":"Pharmacogenom. J."},{"key":"10.1016\/j.jad.2017.11.046_bib18","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/j.1552-4604.1992.tb03875.x","article-title":"Introduction of a composite parameter to the pharmacokinetics of venlafaxine and its active O-desmethyl metabolite","volume":"32","author":"Klamerus","year":"1992","journal-title":"J. Clin. Pharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib19","first-page":"A23","article-title":"Konbest \u2013 a web-based laboratory information management system (LIMS) for TDM-laboratories","volume":"41","author":"K\u00f6stlbacher","year":"2008","journal-title":"Pharmacopsychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib20","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1093\/sleep\/33.11.1553","article-title":"Efficacy and safety of doxepin 1mg and 3mg in a 12-week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia","volume":"33","author":"Krystal","year":"2010","journal-title":"Sleep"},{"key":"10.1016\/j.jad.2017.11.046_bib21","article-title":"Effects of the proton pump inhibitors omeprazole and pantoprazole on the cytochrome P450-mediated metabolism of venlafaxine","author":"Kuzin","year":"2017","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.jad.2017.11.046_bib22","unstructured":"Labbate, L., Fava, M., Rosenbaum, J., Arana, G., 2010. Handbook of Psychiatric Drug Therapy. Philadelphia."},{"key":"10.1016\/j.jad.2017.11.046_bib23","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.sleep.2017.03.007","article-title":"Treatment of insomnia with tricyclic antidepressants: a meta-analysis of polysomnographic randomized controlled trials","volume":"34","author":"Liu","year":"2017","journal-title":"Sleep Med."},{"key":"10.1016\/j.jad.2017.11.046_bib24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1515\/dmdi-2014-0011","article-title":"Clinical drug-drug interactions: focus on venlafaxine","volume":"30","author":"Magalhaes","year":"2015","journal-title":"Drug Metab. Pers. Ther."},{"key":"10.1016\/j.jad.2017.11.046_bib25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/FTD.0000000000000251","article-title":"Risperidone and venlafaxine metabolic ratios strongly predict a CYP2D6 poor metabolizing genotype","volume":"38","author":"Mannheimer","year":"2016","journal-title":"Ther. Drug Monit."},{"key":"10.1016\/j.jad.2017.11.046_bib26","doi-asserted-by":"crossref","first-page":"240","DOI":"10.4088\/JCP.08m04212","article-title":"Polypharmacy in children and adolescents treated for major depressive disorder: a claims database study","volume":"70","author":"McIntyre","year":"2009","journal-title":"J. Clin. Psychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00134-006-0419-8","article-title":"Pharmacokinetic\/pharmacodynamic modelling of cardiac toxicity in venlafaxine overdose","volume":"33","author":"Megarbane","year":"2007","journal-title":"Intensive Care Med."},{"key":"10.1016\/j.jad.2017.11.046_bib28","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1177\/0897190013504957","article-title":"Serotonin syndrome: is it a reason to avoid the use of tramadol with antidepressants?","volume":"27","author":"Park","year":"2014","journal-title":"J. Pharm. Pract."},{"key":"10.1016\/j.jad.2017.11.046_bib29","first-page":"142","article-title":"Richtlinie der GTFCh zur Qualit\u00e4tssicherung bei forensisch-toxikologischen Untersuchungen","volume":"76","author":"Paul","year":"2009","journal-title":"Toxichem Krimtech"},{"key":"10.1016\/j.jad.2017.11.046_bib30","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1177\/0269881116650390","article-title":"Pharmacokinetic considerations in the treatment of hypertension in risperidone-medicated patients \u2013 thinking of clinically relevant CYP2D6 interactions","volume":"30","author":"Paulzen","year":"2016","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.psyneuen.2016.07.009","article-title":"Body mass index (BMI) but not body weight is associated with changes in the metabolism of risperidone; A pharmacokinetics-based hypothesis","volume":"73","author":"Paulzen","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.jad.2017.11.046_bib32","article-title":"Clinical response in a risperidone-medicated naturalistic sample: patients' characteristics and dose-dependent pharmacokinetic patterns","author":"Paulzen","year":"2016","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"10.1016\/j.jad.2017.11.046_bib33","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/01.pra.0000367777.96012.83","article-title":"Understanding outliers on the usual dose-response curve: venlafaxine as a way to phenotype patients in terms of their CYP 2D6 status and why it matters","volume":"16","author":"Preskorn","year":"2010","journal-title":"J. Psychiatr. Pract."},{"key":"10.1016\/j.jad.2017.11.046_bib34","doi-asserted-by":"crossref","first-page":"614","DOI":"10.4088\/JCP.12m07807","article-title":"Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for personalized medicine","volume":"74","author":"Preskorn","year":"2013","journal-title":"J. Clin. Psychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib35","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.3748\/wjg.15.1548","article-title":"Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis","volume":"15","author":"Rahimi","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.jad.2017.11.046_bib36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1055\/s-2007-979552","article-title":"Low serum levels of tricyclic antidepressants in amitriptyline- and doxepin-treated inpatients with depressive syndromes are associated with nonresponse","volume":"29","author":"Rao","year":"1996","journal-title":"Pharmacopsychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib37","series-title":"Potentially Inappropriate Antidepressant Prescriptions Among Older Adults in Office-Based Outpatient Settings: National Trends from 2002 to 2012","author":"Rhee","year":"2017"},{"key":"10.1016\/j.jad.2017.11.046_bib38","first-page":"338","article-title":"Is doxepin a safer tricyclic for the heart?","volume":"52","author":"Roose","year":"1991","journal-title":"J. Clin. Psychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib39","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","article-title":"Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report","volume":"163","author":"Rush","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.jad.2017.11.046_bib40","first-page":"274","article-title":"Antidepressive combination treatment in patients with severe depressive episode: the practice of prescription in a clinical sample 2012","volume":"44","author":"Schmidt-Kraepelin","year":"2017","journal-title":"Psychiatr. Prax."},{"key":"10.1016\/j.jad.2017.11.046_bib41","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/YIC.0000000000000131","article-title":"Risperidone induced extrapyramidal side effects \u2013 is the need for anticholinergics the consequence of high plasma concentrations?","volume":"31","author":"Schoretsanitis","year":"2016","journal-title":"Int. Clin. Psychopharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib42","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1097\/JCP.0000000000000601","article-title":"Pharmacokinetic drug-drug interactions of mood stabilizers and risperidone in patients under combined treatment","volume":"36","author":"Schoretsanitis","year":"2016","journal-title":"J. Clin. Psychopharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.schres.2016.12.016","article-title":"Effect of smoking on risperidone pharmacokinetics \u2013 a multifactorial approach to better predict the influence on drug metabolism","volume":"185","author":"Schoretsanitis","year":"2017","journal-title":"Schizophr. Res."},{"key":"10.1016\/j.jad.2017.11.046_bib44","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s00228-016-2085-2","article-title":"Pharmacokinetic patterns of risperidone-associated adverse drug reactions","volume":"72","author":"Schoretsanitis","year":"2016","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib45","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1365-2710.2006.00763.x","article-title":"CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine","volume":"31","author":"Shams","year":"2006","journal-title":"J. Clin. Pharm. Ther."},{"key":"10.1016\/j.jad.2017.11.046_bib46","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1517\/17425255.2014.885504","article-title":"Clinically relevant interactions between newer antidepressants and second-generation antipsychotics","volume":"10","author":"Spina","year":"2014","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"10.1016\/j.jad.2017.11.046_bib47","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1517\/17425255.2016.1154043","article-title":"Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics","volume":"12","author":"Spina","year":"2016","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"10.1016\/j.jad.2017.11.046_bib48","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2165\/11594710-000000000-00000","article-title":"Clinically significant drug interactions with newer antidepressants","volume":"26","author":"Spina","year":"2012","journal-title":"CNS Drugs"},{"key":"10.1016\/j.jad.2017.11.046_bib49","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/S0026-895X(24)12045-7","article-title":"Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4","volume":"28","author":"Stormer","year":"2000","journal-title":"Drug Metab. Dispos.: Biol. Fate Chem."},{"key":"10.1016\/j.jad.2017.11.046_bib50","first-page":"491","article-title":"Doxepin inhibits CYP2D6 activity in vivo","volume":"56","author":"Szewczuk-Boguslawska","year":"2004","journal-title":"Pol. J. Pharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib51","unstructured":"US Food and Drug Administration, 2001. Guidance for Industry on Biomedical Method Validation. \u3008http:\/\/www.fda.gov\/ucm\/groups\/fdagov-public\/@fdagov-drugs-gen\/documents\/document\/ucm070107.pdf\u3009, (Accessed 23 September 2017)."},{"key":"10.1016\/j.jad.2017.11.046_bib52","unstructured":"US Food and Drug Administration, 2014. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. \u3008http:\/\/www.fda.gov\/Drugs\/DevelopmentApprovalProcess\/DevelopmentResources\/DrugInteractionsLabeling\/ucm093664.htm\u3009, (Accessed 23 September 2017)."},{"key":"10.1016\/j.jad.2017.11.046_bib53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0304-3959(90)91068-T","article-title":"Studies on the effects of antidepressant drugs on the antinociceptive action of morphine and on plasma morphine in rat and man","volume":"43","author":"Ventafridda","year":"1990","journal-title":"Pain"},{"key":"10.1016\/j.jad.2017.11.046_bib54","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s00228-014-1696-8","article-title":"Impact of age on serum concentrations of venlafaxine and escitalopram in different CYP2D6 and CYP2C19 genotype subgroups","volume":"70","author":"Waade","year":"2014","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.jad.2017.11.046_bib55","first-page":"71","article-title":"Efficacy of tramadol in combination with doxepin or venlafaxine in inhibition of nociceptive process in the rat model of neuropathic pain: an isobolographic analysis","volume":"60","author":"Wrzosek","year":"2009","journal-title":"J. Physiol. Pharmacol.: Off. J. Pol. Physiol. Soc."}],"container-title":["Journal of Affective Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S016503271731772X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S016503271731772X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T01:24:54Z","timestamp":1759022694000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S016503271731772X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":55,"alternative-id":["S016503271731772X"],"URL":"https:\/\/doi.org\/10.1016\/j.jad.2017.11.046","relation":{},"ISSN":["0165-0327"],"issn-type":[{"value":"0165-0327","type":"print"}],"subject":[],"published":{"date-parts":[[2018,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Antidepressant polypharmacy and the potential of pharmacokinetic interactions: Doxepin but not mirtazapine causes clinically relevant changes in venlafaxine metabolism","name":"articletitle","label":"Article Title"},{"value":"Journal of Affective Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jad.2017.11.046","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}