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

This version was published on 1 November 2009

Ann Clin Biochem 2009;46:527-530
© 2009 Association for Clinical Biochemistry


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Case Reports

P A H M Wijnen1,*,
I Limantoro2,*,
M Drent3,
O Bekers1,
P M J C Kuijpers4 and
G H Koek2

1 Department of Clinical Chemistry;
2 Department of Internal Medicine, Division of Gastroenterology/Hepatology;
3 Department of Respiratory Medicine, ILD Care Center;
4 Department of Cardiology, Maastricht University Medical Centre (MUMC), Maastricht, The Netherlands

Corresponding author: G H Koek, Department of Internal Medicine, Division of Gastroenterology/Hepatology, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Email: gh.koek{at}

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 metabolicactivity of the corresponding enzymes, thus affecting the subsequentserum drug levels and their metabolites. This case highlightsthe potential benefit of both clinical and genetic risk stratification(pharmacogenetics) prior to treatment, either for setting theindividual dose or for making a decision about using a particulardrug.

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