{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:17:55Z","timestamp":1790983075228,"version":"4.1.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Venlafaxine (VEN) undergoes extensive hepatic metabolism, mainly via CYP2D6. Other minor pathways are also involved in VEN metabolism, some of which have clinical significance, such as the CYP2C19 pathway. Genetic variations in these can impact metabolism, increasing toxicity risk or reducing the medication\u2019s efficacy. While VEN is generally well tolerated, overdose can lead to severe complications, including cardiotoxicity, hypoglycaemia, serotonin syndrome, and seizures, often requiring intensive care unit (ICU) management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>\n                      A 73-year-old female patient was admitted to the emergency department in an unconscious state following a suspected intentional overdose of VEN. Shortly after her admission the patient was transferred to the intensive care unit due to multiorgan failure where she remained for 30 days. Serial VEN level measurements were conducted along with pharmacogenetic testing that revealed a CYP2C19\n                      <jats:italic>poor metabolizer<\/jats:italic>\n                      and a CYP2D6\n                      <jats:italic>intermediate metabolizer<\/jats:italic>\n                      profile, which contributed to high VEN plasma levels that influenced the patient\u2019s prolonged recovery and clinical course.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Genetic polymorphisms affecting VEN metabolism contributed to higher plasma concentrations exceeding 20,000 ng\/mL and, subsequently, to a higher risk of toxicity. The patient developed serotonin syndrome, hypoglycaemia and cardiotoxicity, resulting in cardiogenic shock. A rare combined\n                      <jats:italic>CYP2D6\/CYP2C19<\/jats:italic>\n                      metabolism impairment may have contributed to the severity while age and potential pharmacobezoar formation may further have worsened toxicity and clinical course. This case underscores the importance of early plasma monitoring and pharmacogenetic assessment in overdose management, as a rare metabolic profile affecting VEN clearance contributed to prolonged toxicity and complex ICU management. To our knowledge, this is one of the first cases to describe the potential clinical impact of a rare combined CYP2D6\/CYP2C19 polymorphism.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2026.1943247","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:01:32Z","timestamp":1787724092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Complex venlafaxine overdose and prolonged intensive care unit hospitalization associated to combined CYP2D6 and CYP2C19 polymorphisms"],"prefix":"10.3389","volume":"17","author":[{"given":"Bruno","family":"Michel","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Cliniques universitaires Saint-Luc","place":["Brussels, 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Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Haufroid","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Cliniques universitaires Saint-Luc, Brussels, Belgium & Louvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Exp\u00e9rimentale et Clinique, UClouvain","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao","family":"Pinto Pereira","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Cliniques universitaires Saint-Luc","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1097\/FPC.0000000000000003","article-title":"PharmGKB summary: venlafaxine 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