Preview

Journal of Siberian Medical Sciences

Advanced search

The estimation of influence of CYP3A activity on the efficacy and safety of fluvoxamine in patients with depressive disorders comorbid with alcohol use disorder

https://doi.org/10.31549/2542-1174-2020-1-65-75

Abstract

Introduction. Fluvoxamine is used for treatment of patients with depressive disorders comorbid with alcohol use disorder while a considerable part of this group does not properly respond to therapy, the development of dose-dependent adverse drug effects is noted in many patients. In early studies it was shown that CYP3A is involved in biotransformation of fluvoxamine the activity of which depends in large part on the encoding gene polymorphism.
Aim of the Research. To study CYP3A activity influence on the efficacy and safety profile of fluvoxamine in patients with comorbid depressive disorders and alcohol addiction.
Materials and Methods. 96 males with depressive disorders comorbid with alcohol use disorder took part in the study (average age — 39.9 ± 15.4 years). Fluvoxamine at a dose of 125.0 ± 50.3 mg a day was used for treatment. The efficacy profile was estimated by means of the validated psychometric scales, and the therapy safety profile — by means of the UKU side effects rating scale. Genetic typing was performed by the method of real time PCR . CYP3A activity was estimated by high performance liquid chromatography based on the ratio of endogenous substrate and its metabolite concentrations in urine (6β-hydroxycortisol/cortisol).
Results and Discussion. In the course of the analysis no statistically significant results were obtained in terms of the effectiveness assessment (scores on the HAMD scale by the end of therapy: genotype GG — 4.0 scores [2.0; 8.0], genotype GA — 3.0 scores [1.0; 5.0], p > 0.999) and safety assessment (scores on the UKU scale: genotype GG — 3.0 scores [1.0; 5.0], genotype GA — 4.0 scores [3.0; 4.0], p > 0.999).
Conclusion. In a study conducted in a group of 96 patients with depressive disorders comorbid with alcohol addiction the absence of influence of CYP3A activity on the parameters of clinical efficacy and safety of fluvoxamine was demonstrated.

About the Authors

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

Zastrozhin Mikhail Sergeyevich — Cand. Sci. (Med.), Head, Laboratory of Genetics and Basic Research, Moscow Research and Practical Centre for Narcology; Associate Professor, Drug Addiction Department, Russian Medical Academy of Continuous Professional Education

37/1, Lublinskaya Str., Moscow, 109390



V. V. Smirnov
I.M. Sechenov First Moscow State Medical University; National Research Center — Institute of Immunology
Russian Federation
Smirnov Valeriy Valeryevich — Cand. Sci. (Pharmaceut.), Associate Professor, Pharmaceutical and Toxicological Chemistry Department, I.M. Sechenov First Moscow State Medical University; Head, Laboratory of Pharmacokinetics, National Research Center — Institute of Immunology


A. K. Zastrozhina
Russian Medical Academy of Continuous Professional Education
Russian Federation
Zastrozhina Anastasiya Konstantinovna — Assistant, Pediatrics Department


E. A. Grishina
Russian Medical Academy of Continuous Professional Education
Russian Federation
Grishina Elena Anatolyevna — Dr. Sci. (Biol.), Lead Researcher, Molecular Medicine Division


K. A. Ryzhikova
Russian Medical Academy of Continuous Professional Education
Russian Federation
Ryzhikova Kristina Anatolyevna — Researcher, Molecular Medicine Division


V. Yu. Skryabin
Moscow Research and Practical Centre for Narcology
Russian Federation
Skryabin Valentin Yuryevich — Head, 16 th Drug Addiction Unit


V. V. Shipitsyn
Moscow Research and Practical Centre for Narcology
Russian Federation
Shipitsyn Valeriy Valeryevich — Deputy Medical Director


E. A. Bryun
Moscow Research and Practical Centre for Narcology; Russian Medical Academy of Continuous Professional Education
Russian Federation
Bryun Evgeniy Alekseyevich — Dr. Sci. (Med.), Professor, President, Moscow Research and Practical Centre for Narcology; Head, Drug Addiction Department, Russian Medical Academy of Continuous Professional Education


D. A. Sychev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Sychev Dmitriy Alekseyevich — Corresponding Member (Russian Academy of Sciences), Dr. Sci. (Med.), Professor (Russian Academy of Sciences), Professor, Head, Clinical Pharmacology and Therapy Department, Rector



References

1. Boschloo L., Vogelzangs N., Smit J.H. et al. (2011). 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., 131 (1–3), 233–242.

2. Gautam S., Jain A., Gautam M., Vahia VN., Grover S. (2017). Clinical practice guidelines for the management of depression. Ind. J. Psychiatry, 59 (1), 34–50. doi: 10.4103/0019-5545.196973.

3. Spear B.B., Heath-Chiozzi M., Huff J. (2001). Clinical application of pharmacogenetics. Trends Mol. Med., 7 (5), 201–204. PMID: 11325631.

4. Williams P.A., Cosme J., Vinkovic D.M. et al. (2004). Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science, 305 (5684), 683–686.

5. Klein K., Zanger U.M. (2013). Pharmacogenomics of cytochrome P450 3A4: recent progress toward the “missing heritability” problem. Front. Genet., 4, 12. doi: 10.3389/fgene.2013.00012.

6. Lee J.S., Cheong H.S., Kim L.H. et al. (2013). Screening of genetic polymorphisms of CYP3A4 and CYP3A5 genes. Korean J. Physiol. Pharmacol., 17 (6), 479–484. doi: 10.4196/kjpp.2013.17.6.479.

7. Van Schaik R.H. (2008, Apr). Dose adjustments based on pharmacogenetics of CYP450 enzymes. EJIFCC, 19 (1), 42–47.

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

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

10. Zigmond A.S., Snaith R.P. (1983, Jun). The hospital anxiety and depression scale. Acta Psychiatr. Scand., 67 (6), 361–370.

11. Hamilton M. (1960). A rating scale for depression. J. Neurol. Neurosurg. Psychiatry, 23, 56–62.

12. Lingjaerde O., Ahlfors U.G., Bech P., Dencker S.J., Elgen K. (1987). 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., 334, 76, 1–100.

13. Lutz U., Bittner N., Ufer M., Lutz W.K. (2010, Jan 1). Quantification of cortisol and 6 beta-hydroxycortisol in human urine by LC-MS/MS, and gender-specific evaluation of the metabolic ratio as biomarker of CYP3A activity. J. Chromatogr. B., 878 (1), 97–101. doi: 10.1016/j.jchromb.2009.11.023.

14. Zastrozhin M.S., Grishina E.A., Ryzhikova K.A. et al. (2017, Dec 28). The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction. Pharmgenomics Pers. Med., 11, 1–5. doi: 10.2147/PGPM.S144503.

15. Sychev D.A., Zastrozhin M.S., Miroshnichenko I.I et al. (2017, Sep 26). Genotyping and phenotyping of CYP2D6 and CYP3A isoenzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration. Drug Metab. Pers. Ther., 32(3), 129–136. doi: 10.1515/dmpt-2017-0021.

16. Zastrozhin M.S., Grishina E.A., Denisenko N.P. et al. (2018, Jun 29). Effects of CYP2D6 genetic polymorphisms on the efficacy and safety of fluvoxamine in patients with depressive disorder and comorbid alcohol use disorder. Pharmgenomics Pers. Med., 11, 113–119. doi: 10.2147/PGPM.S160763.

17. Zastrozhin M.S., Sorokin A.S., Agibalova T.V. et al. (2018, Nov). Using a personalized clinical decision support system for bromdihydrochlorphenylbenzodiazepine dosing in patients with anxiety disorders based on the pharmacogenomic markers. Hum. Psychopharmacol., 33 (6), e2677. doi: 10.1002/hup.2677.


Review

For citations:


Zastrozhin M.S., Smirnov V.V., Zastrozhina A.K., Grishina E.A., Ryzhikova K.A., Skryabin V.Yu., Shipitsyn V.V., Bryun E.A., Sychev D.A. The estimation of influence of CYP3A activity on the efficacy and safety of fluvoxamine in patients with depressive disorders comorbid with alcohol use disorder. Journal of Siberian Medical Sciences. 2020;(1):65-75. https://doi.org/10.31549/2542-1174-2020-1-65-75

Views: 206


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2542-1174 (Print)