{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:58:00Z","timestamp":1772499480719,"version":"3.50.1"},"reference-count":40,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The increasing use of antidepressant combinations necessitates a deeper\n                        understanding of drug\u2013drug interactions. This study investigated serum\n                        concentration-dependent CYP2D6 inhibition by bupropion (via\n                        hydroxybupropion) and doxepin at antidepressant doses, using venlafaxine and\n                        risperidone as victim drugs.<\/jats:p>\n                  <jats:p>Therapeutic drug monitoring data from inpatients at the University Hospital\n                        of W\u00fcrzburg (2018\u20132023) were retrospectively analyzed across four\n                        interaction groups (hydroxybupropion\u2013venlafaxine, doxepin\u2013venlafaxine,\n                        doxepin\u2013risperidone, and hydroxybupropion\u2013risperidone) with controls lacking\n                        CYP2D6 inhibitors. Associations between inhibitor concentrations and victim\n                        drug levels were assessed linearly. Nonlinear regression (four-parameter\n                        logistic model) was applied to relate inhibitor concentrations to\n                        metabolite-to-parent ratios; when the model fit was adequate, the\n                        half-maximal inhibitory concentration\/90% inhibitory concentration values\n                        were estimated. Receiver operating characteristic analysis identified\n                        inhibitor concentration thresholds for phenoconversion to poor metabolizer\n                        status.<\/jats:p>\n                  <jats:p>Hydroxybupropion and doxepin concentrations were positively associated with\n                        venlafaxine, risperidone, and venlafaxine active moiety levels\n                        (p\u2009\u2264\u20090.02). Adequate sigmoidal curve fitting demonstrated a\n                        concentration-dependent inverse association between inhibitor levels and\n                        metabolite-to-parent ratios for venlafaxine with hydroxybupropion and\n                        doxepin, and risperidone with hydroxybupropion, but not risperidone with\n                        doxepin. The half-maximal inhibitory concentration values were 120.4\u2009ng\/mL\n                        and 28.16 ng\/mL for hydroxybupropion (venlafaxine and risperidone,\n                        respectively) and 24.4\u2009ng\/mL for doxepin (venlafaxine). Phenoconversion\n                        thresholds were identified for hydroxybupropion (venlafaxine: 328.5\u2009ng\/mL\n                        and risperidone: 110.5\u2009ng\/mL) and doxepin (venlafaxine: 35 ng\/mL and\n                        risperidone: 70.5 ng\/mL).<\/jats:p>\n                  <jats:p>Hydroxybupropion and doxepin exert serum concentration-dependent inhibition\n                        of CYP2D6 activity, significantly affecting the metabolism of venlafaxine\n                        and risperidone. These effects and a phenoconversion into poor metabolizer\n                        status were detectable at subtherapeutic hydroxybupropion and therapeutic\n                        antidepressant doxepin levels. Monitoring inhibitor and victim-drug\n                        concentrations may aid in managing clinically relevant CYP2D6-mediated\n                        interactions.<\/jats:p>","DOI":"10.1055\/a-2812-9208","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T23:57:01Z","timestamp":1772495821000},"source":"Crossref","is-referenced-by-count":0,"title":["Serum Concentration-Dependent Inhibition of CYP2D6 by Bupropion and\n                    Doxepin: Implications for Venlafaxine and Risperidone Metabolism"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9859-8480","authenticated-orcid":false,"given":"Georgios N.","family":"Zioris","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of\n                    Mental Health, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bodo","family":"Warrings","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of\n                    Mental Health, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Deckert","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of\n                    Mental Health, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Institute of Clinical Epidemiology and Biometry,\n                    Julius-Maximilians-Universit\u00e4t W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Walther","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of\n                    Mental Health, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Unterecker","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of\n                    Mental Health, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Department of Psychiatry and Psychotherapy, Social Foundation Bamberg,\n                    Teaching Hospital of the University of Erlangen, Bamberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4780-612X","authenticated-orcid":false,"given":"Maike","family":"Scherf-Clavel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychosomatics and Psychotherapy, Center of\n                    Mental Health, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425787","volume-title":"Diagnostic and Statistical Manual of Mental Disorders. 5th ed., text rev.\n                    Washington, DC: American Psychiatric Association","author":"American Psychiatric Association","year":"2022"},{"issue":"05","key":"ref4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.genhosppsych.2007.06.002","article-title":"Major depression in individuals with chronic medical disorders: prevalence,\n                    correlates and association with health resource utilization, lost productivity\n                    and functional disability","volume":"29","author":"L E Egede","year":"2007","journal-title":"Gen Hosp 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