Pharmacogenetic predictors of the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode


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Resumo

Background. More than 80% of children and adolescents experience adverse reactions while taking antipsychotics. The development of personalized selection of pharmacotherapy is promising. However, the pharmacogenetic studies of the effect of antipsychotics in adolescents have been conducted comparatively more rare than in adult patients. Methods. The study included 101 adolescents with an established diagnosis of acute polymorphic psychotic disorder at admission (F23.0-9, according to ICD-10). All patients received an antipsychotic as their primary therapy. Evaluation of the efficacy and safety of pharmacotherapy was carried out on the 14th day. The psychometric CGAS, PANSS, CGI-S and CGI-I scales were used, as well as the scales for assessing the safety of therapy: UKU SERS, SAS, BARS. All study participants underwent pharmacogenetic testing of pharmacokinetic and pharmacodynamic factors. The assessment of the predictive significance of pharmacogenetic factors for the efficacy and safety of pharmacotherapy was carried out using regression analysis in the SPSS Statistics 21.0 software. Results. “Intermediate" metabolism of CYP2D6 at the trend level towards significance increased the risk of side effects (OR=2.616, 95% CI 0.950-7.203; p=0.063). Carriage of HTR2A rs6313 was combined with a lower UKU SERS “Othersymptoms" subscale score (ß=- 0.289; p=0.003) and an objective assessment according to the BARS akathisia severity scale (ß=-0.217; p=0.029). The carriers of DRD3 rs324026 had a lower BARS akathisia score (ß=-0.349; p=0.004); carriers of DRD3 rs6280 had a lower SAS extrapyramidal symptom score (ß=-0.351; p=0.003). Carriage of ANKS1B rs7968606 was associated with a high SAS score (ß=0.237; p=0.017). Conclusion. An algorithm for the personalized choice of an antipsychotic for adolescents with an acute psychotic episode is proposed based on pharmacogenetic testing of CYP2D6*4, *10, DRD3 rs324026 (allele C), DRD3 rs6280 (allele C), HTR2A rs6313 (genotype TT), and ANKS1B rs7968606 (allele T).

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Sobre autores

Dmitry Ivashchenko

Russian Medical Academy of Continuous Professional Education; Penza Institute for Advanced Training of Doctors - Branch of Russian Medical Academy of Continuous Professional Education

Email: dvi1991@yandex.ru
Senior Researcher, Research Institute for Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education ; Associate Professor at the Department of Psychiatry, Psychiatry-Narcology and Psychotherapy, Penza Institute for Advanced Medical Education - Branch Campus of the Russian Medical Academy of Continuous Professional Education Moscow, Russia

N. Buromskaya

G.E. Sukharev Scientific and Practical Center for Mental Health of Children and Adolescents

Moscow, Russia

P. Shimanov

G.E. Sukharev Scientific and Practical Center for Mental Health of Children and Adolescents

Moscow, Russia

R. Deich

G.E. Sukharev Scientific and Practical Center for Mental Health of Children and Adolescents

Moscow, Russia

I. Dorina

G.E. Sukharev Scientific and Practical Center for Mental Health of Children and Adolescents

Moscow, Russia

M. Nastovich

G.E. Sukharev Scientific and Practical Center for Mental Health of Children and Adolescents

Moscow, Russia

K. Akmalova

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

A. Kachanova

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

E. Grishina

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

L. Savchenko

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

Yu. Shevchenko

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

D. Sychev

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

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