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.

Currently, there is a lack of pharmacogenetic research of antipsychotics’ safety in children and adolescents with acute psychotic episodes. Genetic polymorphisms of CYP2D6 and ABCB1 are the most likely candidates for such studies. AIM.To establish possible associations of CYP3A, CYP2D6, ABCB1 polymorphisms with safety of antipsychotics of an acute psychotic episode in adolescents during the first 14 days of treatment. MATERIALS AND METHODS. We observed 53 adolescents, hospitalized with acute psychotic episode, during 14 days of treatment. Mean age was 15,08±1,7 years. All patients took antipsychotic as the main drug. The tolerance to antipsychotics was assessed using UKU SERS, SAS, BARS. We collected a buccal epitelium from each patient and genotyped CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs7767746), CYP2D6*4, *10 (rs3892097, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) by real-time PCR. RESULTS. Scores of UKU SERS, SAS, BARS, AIMS scales did not correlated with average doses of antipsychotics. Distribution of genetic polymorphisms were in the Hardy-Weinberg equilibrium. The carriage of CYP2D6*4 was associated with the presence of «Asthenia / Lassitude / lncreased Fatigability» (70% vs. 3.6%, p=0.039), the carriage of CYP2D6*10 was associated with «Increased dream activity» (53.8% vs. 22.5%, p=0.043). The «Increased Duration of Sleep» was more often observed in homozygotes according to the polymorphisms ABCB1 2677G>T/A (50% vs. 15.8%, p=0.006) and 3435C>T (41.7% vs. 8.2%, p=0.007). Carriers of TT polymorphism homozygote ABCB1 2677G>T/A also more frequently noted «Polyuria/polydypsia» (37.5% vs. 5.18%, p=0.045). CONCLUSION.Genetic polymorphisms CYP2D6*4, *10, ABCB1 2677G>T/A and 3435C>T increased a risk of adverse drug effects of antipsychotics in adolescents with acute psychotic episode.

The prospective observational study included 101 adolescents diagnosed with acute polymorphic psychotic disorder at the time of admission. Patients were followed up for 14 days. All patients received an antipsychotic as their main therapy. The following scales were used to assess the efficacy and safety of therapy on day 14: CGAS, PANSS, CGI-S, CGI-I, UKU SERS, SAS, BARS. The determination of polymorphic variants of DRD2 (rs1800497, C>T), DRD3 (rs6280, C>T), DRD3 (rs324026, C>T), and DRD4 (rs1800955, C>T) genes was performed by real-time polymerase chain reaction (PCR).

Introduction. Pharmacokinetic genetic factors are prognostically relevant when prescribing antipsychotics to adult patients. Currently, there is a dearth of research on adolescents with an acute psychotic episode. Aim. To identify possible associations of CYP2D6, CYP3A4/5 and ABCB1 gene polymorphic variants with the efficacy and safety of pharmacotherapy in adolescents with an acute psychotic episode within 28 days. Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD- 10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs776746), CYP2D6*4, *9, *10 (rs3892097, rs4986774, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) by real-time PCR. Results. Carriers of ABCB1 2677G>T/A significantly less frequently demonstrated response to pharmacotherapy according to PANSS scale on day 14 compared to GG homozygotes (64.6 % vs. 94.7 %; p=0.014). Carriers of the ABCB1 3435C>T differed by a higher total UKU SERS score on day 14 compared to CC genotype carriers (9.21±5.95 vs. 5.1±4.48; p=0.037). Patients with «intermediate» CYP2D6 metabolism were more likely to have reduced sleep duration (13.6 % vs. 0 %; p=0.031). ABCB1 2677G>T/A (51 % vs. 15.8 %; p=0.012) and 3435C>T (46.6 % vs. 10 %; p=0.039) were more frequently associated with dry mouth. ABCB1 3435C>T carriers were also more likely to have orthostatic vertigo (34.5 % vs. 0 %; p=0.028). Conclusion. Carriage of the ABCB1 3435C>T was associated with greater efficacy of pharmacotherapy for acute psychotic episode in adolescents after 28 days, but also increases the risk of adverse reactions in the first 2 weeks of treatment. The ABCB1 2677G>T/A was associated with an increased risk of adverse reactions as well as less reduction of psychotic symptoms on day 14 of pharmacotherapy.