Carriage of the COMT rs4680 polymorphic variant is associated with better tolerance to antipsychotics in adolescents with an acute psychotic episode: a prospective observational clinical study

Background. Currently, the pharmacogenetics of antipsychotics in adolescents is not well understood. Polymorphic variants of the catechol-o-methyltransferase (COMT) gene have been shown to be important in adults taking antipsychotics for the treatment of schizophrenia. Objective. Evaluation of the predictive role of COMT rs4680 (Val158Met) polymorphic variants for the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode. Methods. The study included 101 adolescents hospitalized for an acute psychotic episode (F23.0-9 according to ICD-10). All patients received an antipsychotic as their main therapy. The patients were followed up for 14 days. The effectiveness of antipsychotics was assessed using the CGAS (Children’s Global Assessment Scale), PANSS (Positive and Negative Symptoms Scale), CGI-S (Clinical Global Impression Severity), and CGI-I (Improvement) scales. The safety of pharmacotherapy was assessed according to the UKU SERS (UKU Side Effects Rating Scale), SAS (Sympson-Angus Scale), BARS (Barnes Akathisia rating scale). Samples of buccal epithelium was obtained from each patient; DNA were extracted, and the carriage of the COMT rs4680 (Val158Met) polymorphic variant was detected by real-time polymerase chain reaction. Statistical analysis was carried out using the SPSS Statistics 21.0 software (IBM Inc, USA). Results. It was found that the carriage of the COMT rs4680 Met polymorphic allele was associated with a lower frequency of certain adverse side effects compared to Val/Val homozygotes: «Deconcentration of attention» (1.3 versus 23.1%; p=0.001), «Orthostatic dizziness» (24 versus 53.8%; p=0.007), the presence of any adverse drug reaction in doctor’s opinion (82.7 versus 100%; p=0.019). No association of COMT rs4680 with antipsychotic efficacy parameters was found. The clarifying analysis performed made it possible to exclude the cross-effect of concomitant pharmacotherapy and other factors on the incidence of adverse side effects. Conclusion. As a result of the study, it was found that the carriage of the COMT rs4680 polymorphic variant is associated with a protective effect against antipsychotic-induced adverse side effects in adolescents with an acute psychotic episode.

pharmacogenetics, antipsychotics, COMT, acute psychotic episode