[Association between polymorphisms of ins/del in the 5-HTT gene and T102C in the 5HTR2A gene and the drug response for escitalopram and nortriptyline in depressed patients]

Abstract

Aim: The role of the Serotonin receptor 5HT2A and Serotonin transporter 5HTTLPR polymorphisms was suggested in the pathogenesis of depression and the therapeutic response to serotonergic drugs. The aim of this study was to find a possible association between polymorphisms of ins/del in the 5-HTT gene and T102C in the 5HTR2A gene and drug response for escitalopram and nortriptyline in depressed patients.

Method: We analysed 90 patients (21 male and 69 females), in the age range 19-68 years, suffering from depressive disorder of at least moderate severity meeting the research criteria of ICD-10 and DSM-IV for major depression. All patients were part of the GENDEP study and were given the written consent for the study. The project was accepted by the local ethics committee. The subjects were randomized to one of the 2 different treatment regimes: (1) patients who received the serotoninergic drug--escitalopram (n=51) with a specified dose range of 10-20 mg/day. (2) patients treated by a noradrenergic drug--nortriptyline (n=39) with the dose range of 75-150 mg/day. The efficacy of treatment was defined by a reduction > or =50% of the total score of the Hamilton scale in the 8th week of treatment. Genotypes for polymorphisms of the ins/del 5-HTT gene and T102C 5HTR2A gene were established by the PCR-RFLP method in the Laboratory of Psychiatric Genetics of the Psychiatric Clinic. Statistical analysis was performed with Statistica version 7.1.

Results: The results of the pharmacogenetic analysis, showed no association between the effects of serotoninergic (escitalopram) or noradrenergic (noradrenaline) therapy and the genotypes or alleles polymorphisms of the 5HTT and 5HTR2A genes.