Study “Biomarkers and personalized pharmacotherapy”, and an associated cohort study in parallel groups of patients “Pharmacogenetic assessment of the safety and effectiveness of therapy with antipsychotics”.

The problem of personalized assessment of the safety of antipsychotic drug therapy remains unsolved, despite numerous studies by clinician-researchers around the world. According to epidemiological studies conducted by WHO, the worldwide prevalence of schizophrenia is approximately 0.8-1.0%. The main antipsychotic medications used to treat schizophrenia are dopamine receptor antagonists, which are of variable efficacy and propensity to provoked adverse reactions. Excessively severe adverse drug reactions often leads to discontinuation of the antipsychotic, low adherence to treatment, and the consequent development of resistance. For “typical” antipsychotics such as haloperidol and chlorpromazine, the most problematic  side effects are extrapyramidal motor symptoms (akathisia, tardive dyskinesia), with a certain risk for iatrogenic metabolic disorders. For “atypical” antipsychotics such as clozapine and olanzepine, there is lesser risk for extrapyramidal symptoms, but common side effects include weight gain, dyslipidemia, type 2 diabetes mellitus, sleep disorders, sexual dysfunction, and neurological disorders. According to generally accepted standards of pharmacogenetic research, it is necessary to take into account the ethnicity of patients when developing algorithms for assessing the genetic risk for adverse reactions to medication. Therefore, we see a need to investigate ethnicity-related genetic factors imparting a risk for antipsychotic side-effects among patients living in the Russian Federation. The present study shall assess the prevalence of polymorphic variants of genes for pharmacokinetic and pharmacodynamic factors associated with the effectiveness and safety of antipsychotics. Results of the study shall inform a project to develop, test, and validate a genetic screening  system for enabling a personalized approach to the prescription of psychopharmacotherapy in the Russian context.

The study is multicenter, conducted in collaboration with the Institute of Personalized Psychiatry and Neurology, V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology (principal investigator – R.F. Nasyrova), with data collection at  the Samara Regional Clinical Psychiatric Hospital. This project is within the framework of the comprehensive project, “Bank of Innovative Neuropsychiatric Research: Priority 2030”, section “Biomarkers and Personalized Pharmacotherapy” (International Centre for Education and Research in Neuropsychiatry).