Associations of polymorphic variants of CYP2C19*2, *17 with effectiveness and safety of sertraline in adolescents with a depressive episode and suicidal tendencies

Objective. To evaluate the associations of carriage of polymorphic variants of CYP2C19*2, *17 with effectiveness and safety of sertraline therapy for 8 weeks in adolescents with a depressive episode and suicidal tendencies. Material and methods. The study included 91 adolescents aged 12—17 years who were hospitalized with a depressive episode and suicidal tendencies. Only patients receiving sertraline were included. The effectiveness and safety of pharmacotherapy using psychometric scales were assessed on days 7 and 21 (inpatient) and week 8 (outpatient) of sertraline therapy. Clinical Global Impression scales (CGI-S and CGI-I), Children’s Global Assessment Scale (CGAS) of mental health and adaptation, Columbia Suicide Severity Rating Scale (C-SSRS), Beck’s Depression Inventory, and Antidepressant Side-Effect Checklist were used. All patients underwent pharmacogenetic testing for CYP2C9*2, *3, and *17. Results. The mean age was 15 [14; 16] years, and 87.9% were females. There were no differences in the CGAS, CGI-S, CGI-I, C-SSRS, and Beck’s Depression Inventory scores for the entire observation period between carriers of CYP2C19*2 and CYP2C19*17 and patients with «wild» genotypes. Carriers of CYP2C19*17 at week 8 of therapy reported more adverse mental effects (1 [0; 2] vs. 0 [0; 1]; p=0.028). After 8 weeks, weakness was more common in CYP2C19*17 carriers (p=0.013), «normal» and «ultra-rapid» CYP2C19 metabolizers (p=0.046). Conclusion. Carriers of the polymorphic variant of CYP2C19*17 more often reported adverse reactions compared to carriers of «wild» genotypes. The result is paradoxical compared to previous studies in adult patients.