CYP2D6 phenotype and ABCB1 haplotypes are associated with antipsychotic safety in adolescents experiencing acute psychotic episodes.

OBJECTIVES: To identify possible associations of CYP2D6, CYP3A4/5, and ABCB1 gene polymorphisms with the efficacy and safety of antipsychotics in adolescents with acute psychotic episodes. METHODS: We examined the associations of pharmacogenetic factors with the efficacy and safety of antipsychotics in 101 adolescents with acute psychotic episodes. The diagnosis on admission was "Brief psychotic disorder" (F23.0-23.9 by ICD-10). All patients were administered antipsychotics for 14 days. Treatment efficacy and safety were assessed using the PANSS, CGAS, CGI-S(I), UKU SERS, BARS, and SAS scales. Pharmacokinetic genotyping was performed for the CYP2D6*4, *10, ABCB1 1236C>T, 2677G>T, and 3435C>T genes. RESULTS: CYP2D6 intermediate metabolisers had "Micturition disturbances" more often than extensive metabolisers (24.2 vs. 7.4%; p=0.026). "Wild" homozygote ABCB1 3435C>T CC was associated with more prominent akathisia. Haplotype analysis of three ABCB1 polymorphisms revealed that the "wild" alleles "C-G-C" (ABCB1 1236-2677-3435) were associated with higher risk of "Reduced salivation" (OR=2.95; 95% CI=1.35-6.45; p=0.0078). CONCLUSIONS: CYP2D6 intermediate metabolism was associated with the risk of urinary difficulties under treatment with antipsychotics. We found that "wild" homozygotes ABCB1 1236C>T, 2677G>T, and 3435C>T were predictors of adverse drug effects caused by treatment with antipsychotics.

CYP2D6 phenotype and ABCB1 haplotypes are associated with antipsychotic safety in adolescents experiencing acute psychotic episodes.

OBJECTIVES: To identify possible associations of CYP2D6, CYP3A4/5, and ABCB1 gene polymorphisms with the efficacy and safety of antipsychotics in adolescents with acute psychotic episodes. METHODS: We examined the associations of pharmacogenetic factors with the efficacy and safety of antipsychotics in 101 adolescents with acute psychotic episodes. The diagnosis on admission was "Brief psychotic disorder" (F23.0-23.9 by ICD-10). All patients were administered antipsychotics for 14 days. Treatment efficacy and safety were assessed using the PANSS, CGAS, CGI-S(I), UKU SERS, BARS, and SAS scales. Pharmacokinetic genotyping was performed for the CYP2D6*4, *10, ABCB1 1236C>T, 2677G>T, and 3435C>T genes. RESULTS: CYP2D6 intermediate metabolisers had "Micturition disturbances" more often than extensive metabolisers (24.2 vs. 7.4%; p=0.026). "Wild" homozygote ABCB1 3435C>T CC was associated with more prominent akathisia. Haplotype analysis of three ABCB1 polymorphisms revealed that the "wild" alleles "C-G-C" (ABCB1 1236-2677-3435) were associated with higher risk of "Reduced salivation" (OR=2.95; 95% CI=1.35-6.45; p=0.0078). CONCLUSIONS: CYP2D6 intermediate metabolism was associated with the risk of urinary difficulties under treatment with antipsychotics. We found that "wild" homozygotes ABCB1 1236C>T, 2677G>T, and 3435C>T were predictors of adverse drug effects caused by treatment with antipsychotics.

Pharmacogenetics of antipsychotics in adolescents with acute psychotic episode during first 14 days after admission: effectiveness and safety evaluation.

OBJECTIVES: Prediction of the antipsychotic's effectiveness is a relevant topic in the field of personalized medicine. METHODS: The 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. RESULTS: We found significantly more frequent "increased dream activity" between CYP2D6 intermediate metabolizers and normal metabolizers (54 vs. 22%; p=0.043). The «increased duration of sleep¼ 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). CONCLUSIONS: We found that CYP2D6 and ABCB1 polymorphisms were associated with the safety of antipsychotics in adolescents with an acute psychotic episode.

Global trigger tool in child psychiatry: Treatment safety evaluation in adolescents with an acute psychotic episode.

OBJECTIVE: To analyse the frequency, structure and risk factors of adverse drug effects in adolescents with acute psychotic episode by the methods of global triggers - Paediatric All-Cause Harm Measurement Tool (PACHMT) and Global Assessment of Paediatric Patient Safety Tool (GAPPS). PATIENTS AND METHODS: We used 151 completed case histories of patients who were admitted to a psychiatric hospital with acute psychotic episode. We applied Global Trigger Tool algorithm to each case retrospectively: we developed a special trigger list for psychiatric patients based on PACHMT, GAPPS and general Global Trigger Tool. We also calculated the Medical Appropriateness Index (MAI) for each case. We applied trigger tool analysis for calculation of treatment safety parameters. Statistical analyses included Pearson's Chi-square, Mann-Whitney U, and Kruskal-Walles tests. RESULTS: We identified a total of 261 triggers among 151 analysed cases, 51 of which were accompanied by adverse drug effects (ADEs) (overall positive prediction value = 19.54%). The value of ADEs per 1000 bed days was 4.73, ADEs per 100 admissions was 33.77%. Extrapyramidal reactions to antipsychotics (58.8%) were the most common ADEs, followed by an abrupt medication stop of one or more drugs due to ADEs (25.5%). Significant predictors of antipsychotic-induced extrapyramidal symptoms were age, MAI score and total number of hospital admissions. CONCLUSION: We recommend three triggers, "Abrupt medication stop", "Prescribing of extrapyramidal symptoms corrector", and "Hospital readmission within 30 days", with reasonable positive predictive value for incorporation into routine systems for patient safety monitoring in adolescents with an acute psychotic episode. Antipsychotic-induced extrapyramidal symptoms were more prevalent in older adolescents and patients with fewer lifetime hospital admissions. These patients need to be carefully monitored to ensure patient safety.