Sertraline safety in adolescents experiencing a depressive episode during first 3 weeks: added anxiolytic matters more than CYP2C19 polymorphisms

Objectives To evaluate the associations of clinical and pharmacogenetic factors (CYP2C19*2, *17 polymorphisms) with the safety parameters of sertraline in adolescents with a depressive episode and suicidal intentions for 3 weeks in a psychiatric hospital. Methods The study included 112 adolescents, who were hospitalized due to a depressive episode and suicidal intentions. All patients received sertraline for 21 days. The safety of pharmacotherapy was assessed on the 7th and 21st day using the Antidepressant ADRs checklist. Each patient underwent genetic testing for CYP2C19*2, *3, *17 . The safety of sertraline was analyzed depending on the carrier status of CYP2C19 polymorphisms, the type of CYP2C19 metabolism, as well as depending on additional pharmacotherapy. Results It was found that patients with the CYP2C19*2 genotype took a slightly lower dose of sertraline compared to those with the wild-type genotype on 21st day (100 [87.5; 100] mg/day vs. 100 [100; 100], p = 0.048). Patients carrying the CYP2C19*17 allele, on the other hand, were more likely to experience vegetative and somatic ADRs on day 7 of treatment (2 vs. 1, p = 0.042). The use of anxiolytics (alimemazine and hydroxyzine) was significantly associated with an increased number of vegetative/somatic, and mental ADRs on day 7, as well as an increased total number of ADRs by day 21. Linear regression analysis confirmed that anxiolytics were the most significant predictors of ADR development on day 21 (Estimate = 0.86, 95% CI 0.32-1.41, p = 0.002). Conclusion Polypharmacy (particularly, adding a non-benzodiazepine anxiolytic) was a more significant risk factor for ADRs when taking sertraline, compared to the carrier status of CYP2C19 gene polymorphisms.