PHARMACOGENETIC ASPECTS OF THE EFFECTIVENESS OF CLOZAPINE THERAPY IN TREATMENT RESISTANT SCHIZOPHRENIA

Abstract

The incidence of treatmentNresistant schizophrenia (TRS) among psychiatric patients currently is estimated to be in the range of 20-40% and remains unchanged over the past decade. Among atypical antipsychotics оnly clozapine is known to have 30-60% efficacy in patients with TRS. Purpose of the study was to identify candidate genes, as well as study and systematization of data on the effect of SNPs on the effectiveness of clozapine therapy in resistant schizophrenia. Methods. Analysis of English and RussianNlanguage literature by keywords was performed. Depth search was 1988 2018 years (30 years). Used the following databases: PubMed, MedLine, Web of Science Core Collection (Clarivate Analytics), Web Science, Russian Science Citation Index, Scopus, Scientific Research, Google Scholar, Oxford Press, eLIBRARY. Results. In total 41 SNPs of serotonin receptor genes isoforms HTR (1A, 2A, 2C, 3A, 3B, 4,6), epinephrine receptor (ADRA2A, ADRB3) and the other SNPs associated with clozapine treatment efficiency was analyzed. An attempt to explain the contradictions obtained during the study was made. Conclusion. SNPs of the serotonergic system genes are perspective markers of the therapeutic response to clozapine in TRS therapy. Univocal results at the moment were obtained only for rs6314 HTR2A. Other SNPs have either a controversial or insufficiently significant contribution to the development of a therapeutic response. It is necessary to conduct multiNcenter studies and pay more attention to features of the effect of SNP candidate genes among different ethnic groups.