Personalised Pharmacotherapy with Sertraline in Patients with Anxiety—Depressive Disorder Based on Omics Biomarkers

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Abstract

Sertraline, a selective serotonin reuptake inhibitor, is widely used as a first-line drug for anxiety and depressive disorders. Clinical efficacy and adverse reactions observed with antidepressants are closely related to the concentration of the drug in the patient’s blood, but the vast majority of antidepressants demonstrate significant pharmacokinetic variability, leading to pronounced interindividual differences in the steady-state concentration of the drug in the blood and its efficacy even with the same dosing regimen. In this regard, it becomes obvious that genetic markers alone are not enough to obtain the most complete profile of the efficacy and safety of a drug; a combination of genotyping methods with omics biomarkers is necessary. As a result of examination of patients diagnosed with mixed anxiety-depressive disorder (F41.2), residents of the Republic of Bashkortostan, it was found that polymorphic variants rs16947 (CYP2D6*2), rs389209 (CYP2D6*4), rs1065852 (CYP2D6*10) of the CYP2D6 gene do not have a significant effect on the activity of CYP2D6. Genetically determined variations in the activity of the CYP2D6 isoenzyme lead to differences in the metabolism of sertraline and its active metabolite N-desmethylsertraline in different patients, which causes variability in their concentrations in blood plasma. A statistically significant increase in the plasma concentrations of sertraline and N-desmethylsertraline was found in patients carrying slow allelic variants rs3892097, rs1065852, rs16947 of the CYP2D6 gene. A statistically significant moderate inverse correlation was found between the dose and the metabolic ratio C6-HO-THBC/CP. The results obtained are preliminary, which makes it necessary to continue the study with an expanded sample size.

About the authors

A. E Gareeva

Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences; Russian Medical Academy of Continuing Professional Education, Ministry of Health of the Russian Federation

Email: annagareeva@yandex.ru
Ufa, Russia; Moscow, Russia

T. R Nasibullin

Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences

Ufa, Russia

S. A Pozdnyakov

Moscow Scientific and Practical Centre of Narcology, Moscow City Health Department

Moscow, Russia

L. S Borodina

Republican Narrological Dispensary, Ministry of Health of the Republic of Bashkortostan № 1

Ufa, Russia

I. F Timerbulatov

Russian Medical Academy of Continuing Professional Education, Ministry of Health of the Russian Federation

Moscow, Russia

N. V Baymeeva

Scientific Center for Mental Health

Moscow, Russia

D. E Bagaev

State Scientific Centre “Institute of Immunology”, Federal Medical and Biological Agency; First Moscow State Medical University I.M. Sechenov, Ministry of Health of the Russian Federation

Moscow, Russia; Moscow, Russia

V. V Smirnov

State Scientific Centre “Institute of Immunology”, Federal Medical and Biological Agency; First Moscow State Medical University I.M. Sechenov, Ministry of Health of the Russian Federation

Moscow, Russia; Moscow, Russia

References

  1. Khedr A., Ali A., Ibrahim T.S., Kammoun A.K. (2025) Preparation and pharmacokinetic evaluation of a sertraline-methylpropyphenazone prodrug: a comparative metabolic study on the plasma and brain tissues of rats using LC-MS/MS analysis. RSC Adv. 15, 2800–2809.
  2. Cipriani A., Furukawa T.A., Salanti G., Chainani A., Atkinson L.Z., Ogawa Y., Leucht S., Ruhe H.G., Turner E.H., Higgins J.P.T., Egger M., Takeshima N., Hayasaka Y., Imai H., Shinohara K., Tajika A., Ioannidis J.P.A., Geddes J.R. (2018) Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 391, 1357–1366.
  3. Bråten L.S., Haslemo T., Jukic M.M., Ingelman-Sundberg M., Molden E., Kringen M.K. (2020) Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients. Neuropsychopharmacology. 45, 570–576.
  4. Lundmark J., Reis M., Bengtsson F. (2000) Therapeutic drug monitoring of sertraline: variability factors as displayed in a clinical setting. Ther. Drug Monit. 22, 446–454.
  5. Hedayati S.S., Gregg L.P., Carmody T., Jain N., Toups M., Rush A.J., Toto R.D., Trivedi M.H. (2017) Effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence: the CAST randomized clinical trial. JAMA. 318, 1876–1890.
  6. Phogole C.M., Hastie R., Kellermann T. (2023) A simple and sensitive LC-MS/MS method for the quantitation of sertraline and N-desmethylsertraline in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1228, 123827.
  7. Colombo A., Cafaro R., Di Bernardo I., Mereghetti M., Cerolini L., Giacovelli L., Giorgetti F., Vanzetto S., Girone N., Savasi V., Cetin I., Clementi E., Bosi M.F., Vigano C.A., Dell'Osso B. (2024) Relevance of pharmacogenetic analyses and therapeutic drug monitoring of antidepressants for an individualized treatment of peripartum psychopathology. Int. Clin. Psychopharmacol. 39, 106–112.
  8. Powelett E.A., Taylor Z.L., Mizuno T., Vaughn S.E., Desta Z., Strawn J.R., Ramsey L.B. (2023) Escitalopram and sertraline population pharmacokinetic analysis in pediatric patients. Clin. Pharmacokinet. 62, 1621–1637.
  9. Zhang Z., Guo Z., Tan Y., Li L., Wang Z., Wen Y., Huang S., Shang D. (2024) Population pharmacokinetic approach to guide personalized sertraline treatment in Chinese patients. Heliyon. 10, e25231.
  10. Rudberg I., Hermann M., Refsum H., Molden E. (2008) Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. Eur. J. Clin. Pharmacol. 64, 1181–1188.
  11. Saiz-Rodriguez M., Belmonte C., Román M., Ochoa D., Koller D., Talegón M., Ovejero-Benito M.C., López-Rodriguez R., Cabaleiro T., Abad-Santos F. (2018) Effect of polymorphisms on the pharmacokinetics, pharmacodynamics and safety of sertraline in healthy volunteers. Basic Clin. Pharmacol. Toxicol. 122, 501–511.
  12. DeVane C.L., Liston H.L., Markowitz J.S. (2002) Clinical pharmacokinetics of sertraline. Clin. Pharmacokinet. 41, 1247–1266.
  13. Смирнов В.В., Абрашин Р.Х., Егоренков Е.А., Гильдеева Г.Н., Раменская Г.В., Пермяков Р.А. (2015) Влияние изофермента CYP2D6 на метаболизм лекарственных препаратов и методы определения его активности. Ведомости Научного центра экспертизы средств медицинского применения. Регуляторные исследования и экспертиза лекарственных средств. 3, 32–35.
  14. Zastrozhin M.S., Skryabin V.Y., Petukhov A.E., Pankratenko E.P., Grishina E.A., Ryzhikova K.A., Torrado M.V., Shipitsyn V.V., Bryun E.A., Sychev D.A. (2021) Impact of CYP2D6 polymorphism on equilibrium concentration of fluoxetine in patients diagnosed with major depressive disorder and comorbid alcohol use disorders. J. Psychiatr. Pract. 27, 372–379.
  15. Castillo C.E.C., Garibay S.E.M., Segovia R.D.C.M., Guzmán S.Z., Cook H.J., Contreras M.O., Moreno S.R. (2024) Population pharmacokinetics of sertraline in psychiatric and substance use disorders. J. Clin. Pharmacol. 64, 1267–1277.
  16. Monfort A. Cardoso E., Eap C.B., Ansermot N., Crettol S., Fischer Fumeaux C.J., Graz M.B., Harari M.M., Weisskopf E., Gandia P., Allegaert K., Annaert P., Nordeng H., Hascoët J.M., Claris O., Epiney M., Ferreira E., Leclair G., Csajka C., Panchaud A., Guidi M.; Collaborators of the SSRI Breast Milk study. (2024) A population pharmacokinetic model for sertraline in women during the perinatal period-A contribution from the ConcePTION project. Br. J. Clin. Pharmacol. 90, 2849–2860.
  17. Preskorn S.H., Greenblatt D.J., Flockhart D., Luo Y., Perloff E.S., Harmatz J.S., Baker B., Klick-Davis A., Desta Z., Burt T. (2007) Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. J. Clin. Psychopharmacol. 27, 28–34.
  18. Jang J.H., Jeong S.H. (2024) Population pharmacokinetic modeling study and discovery of covariates for the antidepressant sertraline, a serotonin selective reuptake inhibitor. Comput. Biol. Med. 183, 109319.
  19. Sychev D.A., Zastrozhin M.S., Smirnov V.V., Grishina E.A., Savchenko L.M., Bryun E.A. (2016) The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction. Pharmgenomics. Pers. Med. 9, 89–95.
  20. Zastrozhin M.S., Skryabin V.Y., Smirnov V.V., Grishina E.A., Ryzhikova K.A., Chumakov E.M., Bryun E.A., Sychev D.A. (2019) Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder. Can. J. Physiol. Pharmacol. 97, 781–785.
  21. Skryabin V., Zastrozhin M., Parkhomenko A., Lauschke V.M., Smirnov V., Petukhov A., Pankratenko E., Pozdnyakov S., Koporov S., Denisenko N., Akmalova K., Bryun E., Sychev D. (2022) Genetic testing is superior over endogenous pharmacometabolomic markers to predict safety of haloperidol in patients with alcohol-induced psychotic disorder. Curr. Drug. Metab. 23, 1067–1071.
  22. Mauri M.C., Laini V., Cerveri G., Scalvini M.E., Volonteri L.S., Regispani F., Malvini L., Manfré S., Boscati L., Panza G. (2002) Clinical outcome and tolerability of sertraline in major depression: a study with plasma levels. Prog. Neuropsychopharmacol. Biol. Psychiatry. 26, 597–601.
  23. Wang J.H., Liu Z.Q., Wang W., Chen X.P., Shu Y., He N., Zhou H.H. (2001) Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin. Pharmacol. Ther. 70, 42–47.
  24. Koe B.K., Weissman A., Welch W.M., Browne R.G. (1983) Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin. J. Pharmacol. Exp. Ther. 226, 686–700.
  25. Owens M.J., Morgan W.N., Plott S.J., Nemeroff C.B. (1997) Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J. Pharmacol. Exp. Ther. 283, 1305–1322.

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