Улогата на генетскиот полиморфизам на CYP 450 како предиктор на тераписки одговор во третман на психози

Abstract

Antipsychotic drugs are widely used in the treatment of schizophrenia and psychotic disorders and there are large inter-individual differences in the clinical response and side effects. Pharmacogenetic testing is a valuable tool for tailoring treatment based on patients' individual genetic markers. The aim of the study was to determine the influence of the CYP2D6 phenotype in the clinical response in patients with psychosis treated with risperidone, hospitalized at the University Clinic of Psychiatry in Skopje, Republic of Northern Macedonia. Material and methods: CYP2D6 genotyping was performed with PGX-CYP2D6 StripAssay® according to the manufacturer's instructions. A total of 91 patients with psychotic disorder diagnosed with ICD10 from F20 - F29 participated in the study. According to the obtained CYP2D6 score, the examined patients were divided into three groups: extensive metabolizers EM (CYP2D6 score 2), moderate / extensive / intermediate metabolizers EM / IM (CYP2D6 score 1) and slow slow metabolizers P2-С6 (CY). Results: 1. The results suggest that the therapeutic effect of antipsychotic therapy evaluated via the PANSS scale was significantly corelated with the genetic polymorphism of CYP2D6. The lowest scores, ie the best therapeutic effects had the extensive metabolizers, while the slow metabolizers had the highest scores for the PANSS scale, ie the weakest therapeutic effects of the antipsychotic treatment. The results also suggest that the therapeutic effect of antipsychotic therapy evaluated on the BPRS scale was significantly corelated with the genetic polymorphism of CYP2D6. The lowest scores, ie the best therapeutic effects had the extensive metabolizers, while the slow metabolizers had the highest scores for the BPRS scale, ie the weakest therapeutic effects of the antipsychotic treatment 2. The final maintenance dose of Risperidone is higher in the examined population of patients with confirmed statistically significant difference between slow and extensive metabolizers (median 5 vs 4 mg, p = 0.026). The difference in the distribution of patients who adhered to and who did not adhere to the treatment protocol was confirmed as statistically significant between the group of slow versus moderate and extensive metabolizers (p = 0.0074, p = 0.0026). 3. Statistical analysis showed that the polymorphisms of CYP2D6 have a significant impact on the occurrence of side effects during treatment with antipsychotic drugs. The six slow metabolites (SM) identified in the study population showed statistically significant multiple adverse reactions compared with patients classified in the group with the phenotype of extensive / intermediate metabolites (EM / IM) or extensive metabolites (EM). 4. The correlation made between the SQLS scale with the two psychiatric scales PANSS and BPRS, in order to see the relationship between the quality of life of patients with schizophrenia and the therapeutic effect of antipsychotic therapy proved to be statistically significant. All three significant correlations are positive, ie direct, and show that increasing the score on the psychiatric scale increased the score on the SQLS scale, and vice versa, patients with lower scores on the PANSS scale for negative and general schizophrenic symptomatology also had lower scores on the SQLS scale. the scale. Patients with a worse therapeutic response to antipsychotic therapy had a worse quality of life, and vice versa. Conclusion: Our study confirmed that the choice of antipsychotic treatment and dose adjustment should be made according to the results of pharmacogenetic tests of CYP2D6 in order to obtain a rational approach to the choice of treatment, control of positive and negative symptoms, appropriate dosing, reduced incidence of adverse events, better patient care, better quality of life and reduced costs.