Early adverse drug reactions to sertraline in adolescents with a depressive episode: assessment of associations with CYP2C19*2, *17 in observational study

Background. An algorithm for the personalized selection of SSRIs based on pharmacogenetic testing is currently available. Personalization algorithms for adults are not applicable to teenagers. Previously, contradictory results were obtained regarding the association of “ultrarapid” CYP2C19 metabolism and poorer tolerability of sertraline and escitalopram. Our aim was to assess the relationships between CYP2C19*2, *3, and *17 polymorphisms and early adverse drug reactions to sertraline among adolescents with depressive episodes and suicidal intentions. Methods. Study design: observational prospective single-center. The study included 133 adolescents (89% female) with a depressive episode and suicidal tendencies. All patients received sertraline. On day 7, the safety of pharmacotherapy was assessed using the Antidepressant adverse drug reactions checklist. Each patient underwent genetic testing for CYP2C19*2, *3, *17. Statistical processing of the results was carried out using IBM SPSS Statistics 26.0. The safety of sertraline was analyzed depending on the carriage of CYP2C19 polymorphisms, the type of CYP2C19 metabolism, as well as depending on additional pharmacotherapy. Results. 96 patients had “normal” CYP2C19 metabolism, 27 had “intermediate” metabolism, 8 — “ultrarapid” metabolism, and 2 — a “poor” metabolism. There were no significant associations of the number of ADRs, as well as the frequency of individual ADRs, depending on the type of CYP2C19 metabolism. Carriage of CYP2C19*17 (CT+TT genotypes) was significantly associated with a large number of somatic and vegetative adverse drug reactions on day 7 (2 (1; 3) vs. 1 (1; 2); p = 0.017). On day 7, carriers of CYP2C19*2 (genotype GA+AA) were more likely to complain of sleep disorders (13 (46.4%) vs. 28 (26.7%); p = 0.044) and tremor (7(25%) vs. 9 (8.7%); p = 0.018) compared with homozygotes GG. Conclusion. Carriage of the CYP2C19*17 was significantly associated with an increase in somatic and vegetative ADRs frequency. This result is paradoxical, as carriage of CYP2C19*17 is more likely to lead to accelerated metabolism of sertraline. Carriage of the CYP2C19*2 was only associated with a higher frequency of sleep disturbances and tremor.