High-dose venlafaxine treatment in a depressed patient with a genetic CYP2D6 deficiency

• Published in: International journal of psychiatry in clinical practice 2004-09, Vol.8 (3), p.191-195
• Main Authors: Haller-gloor, F., Eap, Chin B., Turgeon, Jacques, Baumann, Pierre
• Format: Article
• Language: English
• Subjects: Antidepressants; CYP2D6; CYP2D6 protein; Cytochrome P450; Depression; Drugs; Enantiomers; Genotyping; Lithium; Metabolites; non-response, lithium; pharmacogenetics; plasma concentrations; Remission; Venlafaxine
• ISSN: 1365-1501; 1471-1788; 1473-4885
• DOI: 10.1080/13651500410005559

A female patient (47 years) who suffered from a severe episode of a recurrent depression with psychotic symptoms (F33.3) firstly underwent several unsuccessful treatments. She was then submitted to a combined treatment with 2×300 mg/day extended-release venlafaxine (VEN) and lithium (0.7 mmol/l). She responded within 7 weeks and, after 9 weeks, she showed full remission. Moreover, she tolerated this medication well. Steady-state plasma concentrations of VEN and its metabolites and their enantiomers were measured. The concentrations of VEN and its metabolite O-demethyl-VEN (ODV) were 1024 and 234 ng/ml, respectively. The unusually high concentration of the parent compound in comparison to the metabolite is mainly explained by an impaired metabolism of R-VEN in this patient, who by genotyping was shown to have a genetic deficiency of CYP2D6. In conclusion, in patients suffering from non-response to an antidepressant treatment, an individualised treatment strategy should be developed, and stereoselective therapeutic drug monitoring and genotyping may be recommended.