Case Report: Complex venlafaxine overdose and prolonged intensive care unit hospitalization associated to combined...

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's 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.

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 poor metabolizer and a CYP2D6 intermediate metabolizer profile, which contributed to high VEN plasma levels that influenced the patient's prolonged recovery and clinical course.

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 CYP2D6/CYP2C19 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.