2004 suplement 3

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Volume 13, suplement 3

Pharmakotherapy

Studies on the role of the CYP2D6 activity in depressed patients

MONIKA SZEWCZUK-BOGUSŁAWSKA1, KRYSTYNA ORZECHOWSKA-JUZWENKO2, PIOTR MILEJSKI2, Andrzej Kiejna1, Jan Aleksander Beszłej1, Magdalena Grzesiak1
1. Katedra i Klinika Psychiatrii Akademii Medycznej we Wrocławiu
2. Zakładu Farmakologii Klinicznej Akademii Medycznej we Wrocławiu
Postępy Psychiatrii i Neurologii, 2004, 13, suplement 3 (19), 71-76
Keywords: CYP2D6, depression, sparteine test

Abstract

Aim. Cytochrome 2D6 is involved in oxidation processes of many antidepressant drugs. The CYP2D6 activity is characterized by genetically determined polymorphism. Four phenotypes can be distinguished: ultrarapid (UM), extensive (EM). intermediate (IM) and poor metabolism (PM). Clinical consequences of PM, IM and UM phenotypes may lead to therapeutic failure and the need for hospitalization. In contrast to the healthy population, there are data on the higher rate of PM in hospitalized psychiatric patients. Thus, the aim of this study was to compare the frequency of different CYP2D6 phenotypes in both hospitalized depressed patients and the healthy population.

Method. 52 patients diagnosed with depression according to the ICD-10 and DSM-IV criteria were included in the study. The healthy population consisted of 160 volunteers. CYP2D6 activity was assessed by the phenotyping method. Sparteine was used as a model drug. Each of the patients ingested one tablet containing 100 mg of sparteine sulfate. Urine excreted during the following 6 h was collected. Sparteine and its metabolites (2- and 5-dehydrosparteine) were measured in urine. The metabolic ratio was calculated as the percentage of the dose excreted as sparteine divided by the percentage of the dose excreted as 2- and 5-dehydrosparteine. Based on MR value, the CYP2D6 phenotype was estimated.

Results. There was no statistically significant difference between the frequency of CYP2D6 phenotypes in depressed patients and controls (Fisher exact test p = 0,502). A comparison of sparteine MR values in EM and IM shows statistically significant higher values (median 2,74) in depressed patients than in controls (median 1,75).

Conclusions. The frequency of different CYP2D6 phenotypes does not differ in hospitalized depressed patients in comparison with the healthy population. The CYP2D6 activity in EM and IM is lower in depressed patients than in controls.

Address for correspondence:
Dr Monika Szewczuk-Bogusławska,
Katedra i Klinika Psychiatrii Akademii Medycznej,
ul. Pasteura 10,
53-167 Wrocław,
e-mail: msbog@psych.am.wroc.pl