title: Patients with difficult-to-treat depression do not exhibit an increased frequency of CYP2D6 allele duplication.
abstract: 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.55 patients who failed to respond to 2 or more adequate trials of different CYP2D6-dependent antidepressants were selected for genotyping.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.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.
authors.affiliation: Department of Pharmaceutics, Faculty of Medicine, University of Pécs, Pécs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Háber
authors.forename: O
authors.initials: O
authors.lastname: Rideg
authors.forename: P
authors.initials: P
authors.lastname: Osváth
authors.forename: S
authors.initials: S
authors.lastname: Fekete
authors.forename: F
authors.initials: F
authors.lastname: Szücs
authors.forename: A
authors.initials: A
authors.lastname: Fittler
authors.forename: G L
authors.initials: GL
authors.lastname: Kovács
authors.forename: A
authors.initials: A
authors.lastname: Miseta
authors.forename: L
authors.initials: L
authors.lastname: Botz
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics*; D061218:Depressive Disorder, Treatment-Resistant / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype
chemical_list: D004247:DNA; D019389:Cytochrome P-450 CYP2D6