ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
This article is part of the Research TopicPharmacogenetics and Pharmacogenomics in Psychiatry: Challenges and OpportunitiesView all 7 articles
Sertraline safety in adolescents experiencing a depressive episode during first 3 weeks: added anxiolytic matters more than CYP2C19 polymorphisms
Provisionally accepted
Dmitriy V. Ivashchenko1,2*
Vitaliy V. Sobur3Sergey V. Grass3Anna Y. Basova3Rimma V. Kondratieva3Eugenia N. Shagovenko3Yulia V. Chernetsova3Svetlana N. Tuchkova1,2Ivan N. Korsakov2Sergey I. Markov2
Karin Mirzaev1,2Yuriy S. Shevchenko1
Dmitriy Sychev1,2- 1Russian Medical Academy of Continuous Professional Education, Ministry of Health (Russia), Moscow, Russia
- 2Federal State Budgetary Research Institution «Russian research center of surgery named after academician B.V. Petrovsky», Moscow, Russia
- 3Scientific-Practical Children's and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow, Russia
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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.
Keywords: CYP2C19, Depression, gene, Genetics, Genome, Genotype, Safety, Sertraline
Received: 14 Oct 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Ivashchenko, Sobur, Grass, Basova, Kondratieva, Shagovenko, Chernetsova, Tuchkova, Korsakov, Markov, Mirzaev, Shevchenko and Sychev. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dmitriy V. Ivashchenko
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