Therapeutic Drug Monitoring-Guided Management of Venlafaxine Overdose in an Adolescent: a case report

This report describes an adolescent with severe venlafaxine intoxication in whom serial therapeutic drug monitoring (TDM) was performed, enabling detailed toxicokinetic characterization throughout the clinical course. The initial plasma concentration of the active venlafaxine moiety was 7800 ng/mL, nearly 20 times the upper therapeutic reference limit. On admission, the patient presented with tachycardia, bilateral mydriasis, and generalized tonic-clonic seizures, which are typical clinical manifestations of severe venlafaxine intoxication. Due to progressive impairment of consciousness and increasing oxygen requirements, the patient underwent orotracheal intubation and remained on mechanical ventilation for nearly 120 hours. Serial measurements of venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), provided valuable information on the toxicokinetic progression and supported clinical decision-making regarding the timing of extubation. Despite the extremely elevated venlafaxine concentration, cardiotoxicity was limited to transient QTc prolongation without ventricular arrhythmias and moderate elevations of high-sensitivity troponin I (hs-troponin I) and NT-proBNP. Marked elevations of creatine kinase and myoglobin concentrations were most likely attributable to rhabdomyolysis following general tonic-clonic seizures. TDM demonstrated a progressive increase in the ODV/venlafaxine metabolite-to-parent ratio from 0.30 to 4.50, reflecting the transition from the acute intoxication phase to the elimination phase. The apparent elimination half-life was prolonged to 14.4 hours for venlafaxine and 17.7 hours for ODV. Genotyping revealed the COMT rs4680 Met/Met genotype, which may theoretically influence catecholamine metabolism; however, its contribution to the clinical presentation remains uncertain.