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Polymorphism 3435c> t of the ABCB1 gene (rs1045642) does not affect the mirtazapine efficiency and safety profile in patients with depressive disorders comorbid with alcohol use disorder

https://doi.org/10.20538/1682-0363-2020-4-73-79

Abstract

Background. Mirtazapine is used to treat patients with depressive disorders. A large proportion of patients in this group do not adequately respond to mirtazapine therapy, while many develop undesirable drug reactions of type A. According to the previous studies, P-gp is involved in the biotransformation of mirtazapine, the activity of which is highly dependent on the polymorphism of the gene encoding it.

Aim. The aim of our study was to study the effect of mirtazapine gene polymorphism on the efficacy and safety of mirtazapine therapy in patients with depressive disorders, comorbid with alcohol dependence.

Materials and methods. The study included 119 male patients with depressive disorders, comorbid with alcohol dependence (age 38.7 ± 16.0 years). As a therapy, mirtazapine was used at a dose of 37.8 ± 13.8 mg / day. Evaluation of the effectiveness profile was carried out using psychometric scales. The safety profile was evaluated using the UKU Side-Effect Rating Scale. Genotyping was carried out by polymerase chain reaction in real time.

Results. In the course of the study, results statistically significant in terms of evaluating efficacy and safety were not obtained (HAMD scores at the end of the course of therapy: (CC) 2.5 [2.0; 4.0], (CT) 2.0 [ 1.0; 3.0] and (TT) 2.0 [1.0; 3.0], p > 0.999; according to the UKU scale: (CC) 3.0 [2.8; 3.0], ( CT) 3.0 [3.0; 3.0] and (TT) 3.0 [3.0; 3.0], p > 0.999).

Conclusion. The study of 119 patients with depressive disorders comorbid with alcohol dependence showed that 3435C> T polymorphism of the ABCB1 gene (rs1045642) does not affect the clinical efficacy and safety of mirtazapine.

About the Authors

M. S. Zastrozhin
Moscow Research and Practical Centre on Addictions; Russian Medical Academy of Continuous Professional Education
Russian Federation

37/1, Lyublinskaya Str., Moscow, 109390, Russian Federation

Build. 1, 2/1 Barrikadnaya Str., Moscow, 123995, Russian Federation



E. A. Grishina
Moscow Research and Practical Centre on Addictions
Russian Federation

Build. 1, 2/1 Barrikadnaya Str., Moscow, 123995, Russian Federation



K. A. Ryzhikova
Moscow Research and Practical Centre on Addictions
Russian Federation

Build. 1, 2/1 Barrikadnaya Str., Moscow, 123995, Russian Federation



V. Yu. Skryabin
Russian Medical Academy of Continuous Professional Education
Russian Federation

37/1, Lyublinskaya Str., Moscow, 109390, Russian Federation



S. G. Koporov
Russian Medical Academy of Continuous Professional Education
Russian Federation

37/1, Lyublinskaya Str., Moscow, 109390, Russian Federation

 



E. A. Bryun
Moscow Research and Practical Centre on Addictions; Russian Medical Academy of Continuous Professional Education
Russian Federation

37/1, Lyublinskaya Str., Moscow, 109390, Russian Federation

Build. 1, 2/1 Barrikadnaya Str., Moscow, 123995, Russian Federation



D. A. Sychev
Russian Medical Academy of Continuous Professional Education
Russian Federation
Build. 1, 2/1 Barrikadnaya Str., Moscow, 123995, Russian Federation


References

1. Boschloo L., Vogelzangs N., Smit J.H, van den Brink W., Veltman D.J., Beekman A.T., Penninx B.W. Comorbidity and risk indicators for alcohol use disorders among persons with anxiety and/or depressive disorders: findings from the Netherlands Study of Depression and Anxiety (NESDA). J. Affect Disord. 2011; 131 (1–3): 233–242. DOI: 10.1016/j.jad.2010.12.014.

2. Shiv G., Akhilesh J., Manaswi G. Guidelines for the pharmacological management of depression. Indian J. Psychiatry. 2017; 59 (1): 34–50. DOI: 10.4103/0019-5545.196973.

3. Spear B.B., Heath-Chiozzi M., Huff J. Clinical application of pharmacogenetics. Trends Mol. Med. 2001; 7 (5): 201–204. DOI: 10.1016/s1471-4914(01)01986-4.

4. Peters E.J., Reus V., Hamilton S.P. The ABCB1 transporter gene and antidepressant response. F1000 Biol. Rep. 2009; 1: 23. DOI: 10.3410/B1-23.

5. Wolking S., Schaeffeler E., Lerche H., Schwab M., Nies A.T. Impact of genetic polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on drug disposition and potential clinical implications: update of the literature. Clin. Pharmacokinet. 2015; 54 (7): 709–735. DOI: 10.1007/s40262-015-0267-1.

6. Ieiri I., Takane H., Otsubo K. The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clin. Pharmacokinet. 2004; 43 (9): 553–576. DOI: 10.2165/00003088-200443090-00001.

7. Ahmed S., Zhou Z., Zhou J., Chen S.Q. Pharmacogenomics of drug metabolizing enzymes and transporters: relevance to precision medicine. Genomics Proteomics Bioinformatics. 2016; 14 (5): 298–313. DOI: 10.1016/j.gpb.2016.03.008.

8. Flannery B.A., Volpicelli J.R., Pettinati H.M. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin. Exp. Res. 1999; 23 (8): 1289–1295.

9. Gould D., Kelly D., Goldstone L., Gammon J. Visual Analogue Scale (VAS). Journal of Clinical Nursing. 2001; 10 (5): 697–706. DOI: 10.1046/j.1365-2702.2001.00525.x.

10. Busner J., Targum S.D. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). 2007; 4 (7): 28–37.

11. Zigmond A.S., Snaith R.P. The hospital anxiety and depression scale. Acta Psychiatr. Scand. 1983; 67 (6): 361–370. DOI: 10.1111/j.1600-0447.1983.tb09716.x.

12. Hamilton M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry. 1960; 23 (1): 56–62. DOI: 10.1136/jnnp.23.1.56.

13. Lingjaerde O., Ahlfors U.G., Bech P., Dencker S.J., Elgen K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr. Scand. Suppl. 1987; 334: 1–100. DOI: 10.1111/j.1600-0447.1987.tb10566.x.

14. Zastrozhin M.S., Skryabin V.Y., Smirnov V.V., Grishina E.A., Ryzhikova K.A., Chumakov E.M., Bryun E.A., Sychev D.A. 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. 2019; 97 (8): 781–785. DOI: 10.1139/cjpp-2019-0177.

15. Zastrozhin M.S., Sorokin A.S., Agibalova T.V., Grishina E.A., Antonenko A.Р., Rozochkin I.N., Duzhev D.V., Skryabin V.Y., Galaktionova T.E., Barna I.V., Orlova A.V., Aguzarov A.D., Savchenko L.M., Bryun E.A., Sychev D.A. Using a personalized clinical decision support system for bromdihydrochlorphenylbenzodiazepine dosing in patients with anxiety disorders based on the pharmacogenomic markers. Hum. Psychopharmacol. 2018; 33 (6): e2677. DOI: 10.1002/hup.2677.

16. Zastrozhin M.S., Skryabin V.Y., Miroshkin S.S., Bryun E.A., Sychev D.A. Pharmacogenetics of alcohol addiction: current perspectives. Appl. Clin. Genet. 2019; 12: 131–140. DOI: 10.2147/TACG.S206745.


Review

For citations:


Zastrozhin M.S., Grishina E.A., Ryzhikova K.A., Skryabin V.Yu., Koporov S.G., Bryun E.A., Sychev D.A. Polymorphism 3435c> t of the ABCB1 gene (rs1045642) does not affect the mirtazapine efficiency and safety profile in patients with depressive disorders comorbid with alcohol use disorder. Bulletin of Siberian Medicine. 2020;19(4):73-79. https://doi.org/10.20538/1682-0363-2020-4-73-79

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ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)