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Pharmacopsychiatry 2013; 46(04): 156-160
DOI: 10.1055/s-0033-1343397
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Patients with Difficult-to-Treat Depression Do not Exhibit an Increased Frequency of CYP2D6 Allele Duplication

Á. Háber
1   Department of Pharmaceutics, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
O. Rideg
2   Institute of Laboratory Medicine, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
P. Osváth
3   Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
S. Fekete
3   Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
F. Szücs
1   Department of Pharmaceutics, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
A. Fittler
1   Department of Pharmaceutics, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
G. L. Kovács
2   Institute of Laboratory Medicine, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
A. Miseta
2   Institute of Laboratory Medicine, Faculty of Medicine, University of Pécs, Pécs, Hungary
,
L. Botz
1   Department of Pharmaceutics, Faculty of Medicine, University of Pécs, Pécs, Hungary
› Author Affiliations
Further Information

Publication History

received 11 September 2012
revised 27 February 2013

accepted 08 March 2013

Publication Date:
04 June 2013 (online)

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Abstract

Introduction:

The insufficient response of patients to antidepressant medications may result from several factors, including altered drug metabolism. CYP2D6 genotyping may help assess the possible factors that contribute to difficult-to-treat depression. The aim of our study was to determine the frequency of CYP2D6 allelic variants and the prevalence of predicted CYP2D6 phenotypes in patients who were suffering from difficult-to-treat depression and compare the data with those for the healthy population of Hungary.

Methods:

55 patients who failed to respond to 2 or more adequate trials of different CYP2D6-dependent antidepressants were selected for genotyping.

Results:

The prevalence of the predicted CYP2D6 phenotypes in the patient population was 1.8% for the UMs, 80.0% for EMs, 3.6% for IMs and 14.5% for PMs compared with 1.9% for UMs, 83.3% for EMs, 6.5% for IMs and 8.3% for PMs in the Hungarian population.

Discussion:

The CYP2D6 allele frequencies and the predicted phenotype distributions in patients with difficult-to-treat depression were not significantly different to those found in the healthy population of Hungary. The cumulative frequency of the CYP2D6*1XN, *2XN and *35XN alleles was 0.9% in the patient population ­suggesting that CYP2D6 duplication or multiplication does not play a significant role in antidepressant pharmacotherapy failure in this patient sample. The cumulative frequency of the non-functional alleles (33.5%) and the prevalence of the genetically determined PM phenotype (14.5%) were relatively high in the patient group. These figures draw attention to the possibility of unrecognised and non-reported side effects and non-adherence to drug treatment.

Key words

major depressive disorder - difficult-to-treat depression - CYP2D6 genotyping - CYP2D6 allele duplication - ultrarapid metaboliser ­phenotype
 

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