Plasma levels and cerebrospinal fluid penetration of venlafaxine in a patient with a non-fatal overdose during a suicide attempt

Introduction: We report the case of a 37-year-old female inpatient surviving a suicide attempt with 100 tablets of 150mg (15g) of venlafaxine. Method: Therapeutic drug monitoring (TDM) of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) in both, plasma and CSF, revealed extraordinary high drug levels. For cytochrome P450 2D6, she was found to be an extensive metabolizer (EM) with the genotype *1/*1. Concerning the ABCB1 C3435T genotype, she was found to be CT, reflecting an intermediate phenotype which is the most common one. Results: Therapeutic drug monitoring (TDM) showed plasma-levels for VEN of 18,138ng/mL, ODV 2,955ng/mL (active moiety 21,093ng/mL). CSF-levels were found to be 6,488ng/mL for VEN and 2,154 for ODV. Conclusion: The toxicity of the extraordinary plasma- and CSF-levels of VEN + ODV was comparably low. By genotyping the patient for the ABCB1 gene, we hoped to find a reason for the high penetration rate into the CSF but it seems impossible to predict the consequence of a genetic ABCB1 polymorphism disregarding that the high levels of VEN and ODV resulted in a saturation of the p-GP pumps. Apparently, ABCB1 genotyping explains only part of the variability of P-gp activity in humans. Further research is needed addressing the characteristics of the BBB function and its regulation of the uptake and the excretion of psychotropic drugs in and out of CSF.