В 2016 г. кафедра детской психиатрии и психотерапии Российской медицинской академии последипломного образования (в прошлом-ЦИУВ-Центральный институт усовершенствования врачей) отметила свое 80-летие. Основателем этой кафедры являлась Груня Ефимовна Сухарева, которой в 2016 г. исполнилось бы 125 лет со дня рождения. Она по праву считается основоположником детской психиатрии в нашей стране. За многие годы руководства кафедрой Г.Е. Сухарева с сотрудниками подготовила несколько поколений детских психиатров, создала собственную научную школу и внесла существенный вклад в науку и практику важнейшей медицинской специальности. Родилась Груня Ефимовна Сухарева 11 ноября 1891 г. в Киеве. В 1915 г. она окончила медицинское отделение Киевских высших женских курсов (с 1916 г.-Женский медицинский институт), после чего в течение 2 лет работала врачом эпидемиологического отряда. В 1917 г. она стала ординатором в Киевской психиатрической больнице, а затем там же работала врачом, одновременно исполняя обязанности ассистента и заведующей секцией дефектологии во врачебно-педагогическом институте. С этого периода началась научная деятельность Г.Е. Сухаревой. Одной из первых ее работ было выполненное в 1920 г.

ObjectivesPrediction of the antipsychotic’s effectiveness is a relevant topic in the field of personalized medicine.MethodsThe research design of this study is a prospective observation with posthoc analysis of associations of genetic polymorphisms with safety parameters and effectiveness of antipsychotic therapy. We observed 53 adolescents with an acute psychotic episode which were prescribed antipsychotics for 14 days. We evaluated the effectiveness of antipsychotics with the Positive and Negative Symptoms Scale and the safety with the UKU Side Effects Rating Scale, Simpson-Angus Scale, and Barnes Akathisia rating scale. We genotyped CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs7767746), CYP2D6*4, *9, *10 (rs3892097, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642), DRD2 (rs1800497), DRD4 (rs1800955), HTR2A (rs6313) by the real-time polymerase chain reaction method.ResultsWe found significantly more frequent “increased dream activity” between CYP2D6 intermediate metabolizers and normal metabolizers (54 vs. 22%; p=0.043). The «increased duration of sleep» was more often observed in homozygotes TT of ABCB1 2677G>T/A (50 vs. 15.8%, p=0.006) and TT of 3435C>T (41.7 vs. 8.2%, p=0.007).ConclusionsWe found that CYP2D6 and ABCB1 polymorphisms were associated with the safety of antipsychotics in adolescents with an acute psychotic episode.

Children and adolescents are more likely than adults to experience adverse side effects when taking antipsychotics. Pharmacogenetic testing allows one to more accurately choose the initial dose of a drug. The genes of pharmacokinetic factors have been shown to be of high prognostic value for the safety of antipsychotics in adults.Patients and methods. The study enrolled 36 adolescents (58.3% male) (mean age, 14.83±1.84 years). All the patients took an antipsychotic. The follow-up lasted 28 days. On 14 and 28 days of treatment, its efficiency and safety were evaluated using the Children's Global Assessment Scale (CGAS), the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersњgelser Side Effects Rating Scale (UKU-SERS), the Simpson-Angus Scale (SAS), and the Barnes Akathisia Rating Scale (BARS). The patients were genotyped for CYP3A4*22, CYP3A5*3, CYP2D6*4, *9, *10, ABCB1 1236C>T, 2677G>T/A, 3435C>T, DRD2 rs1800497, DRD4 rs1800955, and HTR2A rs6313.Results and discussion. The decrease in the mean score of the PANSS subscale “Productive symptoms” was more pronounced in carriers of the DRD2 rs1800497 polymorphic variant (-6.5 [-10.25; -3.75] vs -3 [-6.5; -2 ] on 14 day (p=0.028) and (-11 [-13; -9.5] vs -5 [-9; -3.5] on 28 day (p=0.001) compared to baseline. The carriage of ABCB1 3435CT+TT was associated with worse tolerance to pharmacotherapy on 14 day (the total score of the UKU-SERS M, 8 [3; 11.75] vs M, 2 [1; 6]; p=0.034). The carriers of DRD2 rs1800497 reported a greater severity of antipsychotic-induced neurological disorders (UKU-SERS subscale score M, 1 [0; 2.25] vs M 0 [0; 1]; p=0.029).Conclusion. The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T were established to be significantly associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode.

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Antipsychotics are often used to treat children and adolescents. Because of their age, there are a lot of off-label prescribed antipsychotics in that population. However, the off-label use of medications is considered to be potentially unsafe.Objective: to evaluate whether the off-label prescription of antipsychotics outside of the approved age group increased the risk of adverse drug reactions in adolescents experiencing an acute psychotic episode.Patients and methods. We analyzed 450 charts of adolescents hospitalized due to an acute psychotic episode (only completed cases). In addition, we evaluated adverse drug reactions adjusted by off-label antipsychotics prescription outside the approved age group using the Global Trigger Tool (GTT). We also registered prescriptions with duplicates drug classes and potentially dangerous drug interactions.Results and discussion. Off-label antipsychotics prescription outside the approved age group was less frequently associated with adverse drug reactions (3.2% vs. 10.5%; p=0.013). The logistic regression analysis did not show any significant associations between the off-label antipsychotic use and increased risk of adverse drug reactions (Odds ratio=0.994 (95% confidence interval 0.572-1.726), p=0.982). Although, patients with off-label use of antipsychotics were more likely to have potentially dangerous drug interactions (35.2% vs. 16.15%; p=0.0001) and prescriptions with duplicates drug classes (39.6% vs. 15.43%; p=0.0001).Conclusion. Off-label antipsychotic prescription outside the approved age group in adolescents with acute psychotic episode does not increase the risk of adverse drug reactions. However, an increase in potentially dangerous drug interactions and prescriptions with duplicates drug classes frequency could be considered red flags. Therefore, we have concluded that the concerns about off-label antipsychotics prescription outside of approved age groups in adolescents with acute psychotic episodes were overrated.