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

Ivashchenko D.V.; Grass S.V.; Sobur V.V.; Shimanov P.V.; Shubin A.V.; Deich R.V.; Kondratieva R.V.; Shagovenko E.N.; Chernetsova Yu.V.; Tuchkova S.N.; Denisenko N.P.; Mirzaev K.B.; Basova A.Ya.; Shevchenko Yu.S.; Sychev D.A.

doi:https://doi.org/10.17116/jnevro202512510212

Ivashchenko D.V.

Russian Medical Academy of Continuing Professional Education

ORCID: 0000-0002-2295-7167

Grass S.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0009-0007-3327-5130

Sobur V.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-3162-2115

Shimanov P.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-9050-4776

Shubin A.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0009-0009-2963-8052

Deich R.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0001-7154-2999

Kondratieva R.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-9576-8447

Shagovenko E.N.

Russian Medical Academy of Continuing Professional Education

ORCID: 0009-0002-9016-5521

Chernetsova Yu.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0009-0001-0631-4997

Tuchkova S.N.

Russian Medical Academy of Continuing Professional Education

ORCID: 0009-0001-2744-2752

Denisenko N.P.

Russian Medical Academy of Continuing Professional Education

ORCID: 0000-0003-3278-5941

Mirzaev K.B.

Russian Medical Academy of Continuous Postgraduate Education

ORCID: 0000-0002-9307-4994

Basova A.Ya.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-5001-8554

Shevchenko Yu.S.

Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0001-9871-8704

Sychev D.A.

Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0002-4496-3680

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

Authors:

Ivashchenko D.V., Grass S.V., Sobur V.V., Shimanov P.V., Shubin A.V., Deich R.V., Kondratieva R.V., Shagovenko E.N., Chernetsova Yu.V., Tuchkova S.N., Denisenko N.P., Mirzaev K.B., Basova A.Ya., Shevchenko Yu.S., Sychev D.A.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(10‑2): 12‑20

DOI: 10.17116/jnevro202512510212

Read: 376 times

Contact the author

Table of contents

To cite this article:

Ivashchenko DV, Grass SV, Sobur VV, et al. . Associations of polymorphic variants of CYP2C19*2, *17 with effectiveness and safety of sertraline in adolescents with a depressive episode and suicidal tendencies. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(10‑2):12‑20. (In Russ.)
https://doi.org/10.17116/jnevro202512510212

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова. Спецвыпуски (S.S. Korsakov Journal of Neurology and Psychiatry (special issues))

Использование инфографики авторами научных работ

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.

Keywords:

antidepressants

adolescents

pharmacogenetics

sertraline

CYP2C19

safety

effectiveness

Authors:

Ivashchenko D.V.

Russian Medical Academy of Continuing Professional Education

ORCID: 0000-0002-2295-7167

Grass S.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0009-0007-3327-5130

Sobur V.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-3162-2115

Shimanov P.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-9050-4776

Shubin A.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0009-0009-2963-8052

Deich R.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0001-7154-2999

Kondratieva R.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-9576-8447

Shagovenko E.N.

Russian Medical Academy of Continuing Professional Education

ORCID: 0009-0002-9016-5521

Chernetsova Yu.V.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0009-0001-0631-4997

Tuchkova S.N.

Russian Medical Academy of Continuing Professional Education

ORCID: 0009-0001-2744-2752

Denisenko N.P.

Russian Medical Academy of Continuing Professional Education

ORCID: 0000-0003-3278-5941

Mirzaev K.B.

Russian Medical Academy of Continuous Postgraduate Education

ORCID: 0000-0002-9307-4994

Basova A.Ya.

Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva

ORCID: 0000-0002-5001-8554

Shevchenko Yu.S.

Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0001-9871-8704

Sychev D.A.

Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0002-4496-3680

Received:

06.05.2025

Accepted:

07.06.2025

Close metadata

References:

Rynn MA, Walkup JT, Compton SN, et al. Child/Adolescent anxiety multimodal study: evaluating safety. J Am Acad Child Adolesc Psychiatry. 2015;54(3):180-190. https://doi.org/10.1016/j.jaac.2014.12.015
Souery D, Serretti A, Calati R, et al. Switching antidepressant class does not improve response or remission in treatment-resistant depression. J Clin Psychopharmacol. 2011;31(4):512-516. https://doi.org/10.1097/JCP.0B013E3182228619
Lukmanji A, Pringsheim T, Bulloch AG, et al. Antidepressant Prescriptions, Including Tricyclics, Continue to Increase in Canadian Children. J Child Adolesc Psychopharmacol. 2020;30(6):381-388. https://doi.org/10.1089/cap.2019.0121
Cipriani A, Zhou X, Del Giovane C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet. 2016;388(10047):881-890. https://doi.org/10.1016/S0140-6736(16)30385-3
Wehry AM, Beesdo-Baum K, Hennelly MM, et al. Assessment and treatment of anxiety disorders in children and adolescents. Curr Psychiatry Rep. 2015;17(7):52. https://doi.org/10.1007/s11920-015-0591-z
Milosavljević F, Molden PE, Ingelman-Sundberg PM, et al. Current level of evidence for improvement of antidepressant efficacy and tolerability by pharmacogenomic-guided treatment: A Systematic review and meta-analysis of randomized controlled clinical trials. Eur Neuropsychopharmacol. 2024;81:43-52. https://doi.org/10.1016/J.EURONEURO.2024.01.005
Arnone D, Omar O, Arora T, et al. Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials. Neurosci Biobehav Rev. 2023;144:104965. https://doi.org/10.1016/J.NEUBIOREV.2022.104965
Bunka M, Wong G, Kim D, et al. Evaluating treatment outcomes in pharmacogenomic-guided care for major depression: A rapid review and meta-analysis. Psychiatry Res. 2023;321. https://doi.org/10.1016/j.psychres.2023.115102
Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68. https://doi.org/10.1002/cpt.2903
Maruf A Al, Greenslade A, Arnold PD, Bousman C. Antidepressant pharmacogenetics in children and young adults: A systematic review. J Affect Disord. 2019;254:98-108. https://doi.org/10.1016/j.jad.2019.05.025
Roberts B, Cooper Z, Lu S, et al. Utility of pharmacogenetic testing to optimise antidepressant pharmacotherapy in youth: a narrative literature review. Front Pharmacol. 2023;14. https://doi.org/10.3389/FPHAR.2023.1267294
Brent D, Melhem N, Ferrell R, et al. Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Am J Psychiatry. 2010;167(2):190-197. https://doi.org/10.1176/appi.ajp.2009.09040576
Gassó P, Rodríguez N, Blázquez A, et al. Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine. Prog Neuropsychopharmacol Biol Psychiatry. 2017;75:28-34. https://doi.org/10.1016/j.pnpbp.2016.12.003
Blázquez A, Gassó P, Mas S, et al. One-Year Follow-up of Children and Adolescents with Major Depressive Disorder: Relationship between Clinical Variables and Abcb1 Gene Polymorphisms. Pharmacopsychiatry. 2016;49(6):248-253. https://doi.org/10.1055/s-0042-108202
Strawn JR, Mills JA, Schroeder H, et al. Escitalopram in Adolescents With Generalized Anxiety Disorder: A Double-Blind, Randomized, Placebo-Controlled Study. J Clin Psychiatry. 2020;81(5):20m13396. https://doi.org/10.4088/JCP.20m13396
Poweleit EA, Aldrich SL, Martin LJ, et al. Pharmacogenetics of sertraline tolerability and response in pediatric anxiety and depressive disorders. J Child Adolesc Psychopharmacol. 2019;29(5):348-361. https://doi.org/10.1089/cap.2019.0017
Rossow KM, Aka IT, Maxwell-Horn AC, et al. Pharmacogenetics to Predict Adverse Events Associated With Antidepressants. Pediatrics. 2020;146(6):e20200957. https://doi.org/10.1542/peds.2020-0957
Vande Voort JL, Orth SS, Shekunov J, et al. A Randomized Controlled Trial of Combinatorial Pharmacogenetics Testing in Adolescent Depression. J Am Acad Child Adolesc Psychiatry. 2022;61(1):46-55. https://doi.org/10.1016/J.JAAC.2021.03.011
Ivanets NN, Kinkulkina MA, Tikhonova YuG, et al. The association between the 5-HTTLRP polymorphism of the serotonin transporter gene and the efficacy and tolerability of selective serotonin reuptake inhibitors. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(2):46-51. (In Russ.). https://doi.org/10.17116/jnevro20161162146-51
Ivanets NN, Kinkulkina MA, Tikhonova YuG, et al. Analysis of prognostic value of CYP2D6 polymorphisms in the occurrence of adverse events of antidepressant treatment. Psihiatriia I psihofarmacoterapiia. 2015;17(5-6):46-51. (In Russ.).
Zastrozhin MS, Skryabin VY, Petukhov AE, et al. Impact of CYP2D6 Polymorphism on Equilibrium Concentration of Fluoxetine in Patients Diagnosed With Major Depressive Disorder and Comorbid Alcohol Use Disorders. J Psychiatr Pract. 2021;27(5):372-379. https://doi.org/10.1097/PRA.0000000000000568
Shaffer D, Gould MS, Brasic J, et al. A Children’s Global Assessment Scale (CGAS). Arch Gen Psychiatry. 1983;40(11):1228. https://doi.org/10.1001/archpsyc.1983.01790100074010
Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007;4(7):28-37.
Tsukarzi EE. Suicide: risk assessment and first aid. Determining the level of suicide risk using the Columbia Suicide Severity Rating Scale (C-SSRS). Sovremennaya terapiya psihicheskih rasstrojstv. 2011;(2):30-40. (In Russ.).
Posner K, Brown GK, Stanley B, et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168(12):1266-1277. https://doi.org/10.1176/appi.ajp.2011.10111704
Beck AT, Ward CH, Mendelson M, et al. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4(6):561-571. https://doi.org/10.1001/ARCHPSYC.1961.01710120031004
Brouwer JMJL, Nijenhuis M, Soree B, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2C19 and CYP2D6 and SSRIs. Eur J Hum Genet. 2022;30(10):1114-1120. https://doi.org/10.1038/S41431-021-01004-7
Hardy Weinberg equilibrium online calculator. https://www.had2know.org/academics/hardy-weinberg-equilibrium-calculator-2-alleles.html
Huddart R, Hicks JK, Ramsey LB, et al. PharmGKB summary: sertraline pathway, pharmacokinetics. Pharmacogenet Genomics. 2020;30(2):26-33. https://doi.org/10.1097/FPC.0000000000000392
De Vane CL, Liston HL, Markowitz JS. Clinical pharmacokinetics of sertraline. Clin Pharmacokinet. 2002;41(15):1247-1266. https://doi.org/10.2165/00003088-200241150-00002