Depressive effect of an antidepressant: therapeutic failure of venlafaxine in a case lacking CYP2D6 activity.

Understanding the mechanisms of drug metabolism and interactions can help to prevent side-effects. Not only drug interactions, environmental factors, disease processes and ageing are factors in the inter-individual metabolic capacity variance but also genetic factors probably play an important role, as is illustrated in the case presented. Besides therapeutic drug monitoring, genotyping some important cytochrome P450 (CYP450) enzymes was of additional value in explaining why the patient developed severe adverse effects and, moreover, did not experience any therapeutical effect of venlafaxine. Results indicated that the patient was a poor metabolizer for CYP2D6, the most important phase I enzyme to metabolize venlafaxine. This corroborates that polymorphisms in the CYP450 gene influence the metabolic activity of the corresponding enzymes, thus affecting the subsequent serum drug levels and their metabolites. This case highlights the potential benefit of both clinical and genetic risk stratification (pharmacogenetics) prior to treatment, either for setting the individual dose or for making a decision about using a particular drug.