دورية أكاديمية
Effect of Genetic Polymorphism of the CYP2D6 Gene on the Efficacy and Safety of Fluvoxamine in Major Depressive Disorder.
| العنوان: | Effect of Genetic Polymorphism of the CYP2D6 Gene on the Efficacy and Safety of Fluvoxamine in Major Depressive Disorder. |
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| المؤلفون: | Zastrozhin M; Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation., Skryabin V; Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia., Smirnov V; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia; and.; NRC Institute of Immunology FMBA of Russia, Moscow, Russia., Zastrozhina A; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation., Grishina E; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation., Ryzhikova K; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation., Bure I; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation., Golovinskii P; Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia., Koporov S; Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia., Bryun E; Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation., Sychev D; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. |
| المصدر: | American journal of therapeutics [Am J Ther] 2021 Jun 03; Vol. 29 (1), pp. e26-e33. Date of Electronic Publication: 2021 Jun 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9441347 Publication Model: Electronic Cited Medium: Internet ISSN: 1536-3686 (Electronic) Linking ISSN: 10752765 NLM ISO Abbreviation: Am J Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Philadelphia, PA : Lippincott Williams & Wilkins Original Publication: New York, NY : Chapman & Hall, c1994- |
| مواضيع طبية MeSH: | Depressive Disorder, Major*/drug therapy , Depressive Disorder, Major*/genetics , MicroRNAs*, Cytochrome P-450 CYP2D6/genetics ; Fluvoxamine/adverse effects ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Tandem Mass Spectrometry |
| مستخلص: | Background: Previous studies have shown that cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of fluvoxamine, the activity of which is highly dependent, inter alia, on the polymorphism of the gene encoding it. The objective of our study was to investigate the effect of 1846G>A polymorphism of the CYP2D6 gene on the efficacy and safety of fluvoxamine, using findings on CYP2D6 enzymatic activity and on CYP2D6 expression level in patients with depressive disorders comorbid with alcohol use disorder. Study Question: Efficacy and safety of fluvoxamine depend on the polymorphism of CYP2D6 gene in patients with major depressive disorder. Study Design: Our study enrolled 96 male patients with depressive disorders comorbid with alcohol use disorder. Patients were examined on days 1, 9, and 16 of fluvoxamine therapy. Measures and Outcomes: Treatment efficacy was evaluated using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6-hydroxy-1,2,3,4-tetrahydro-β-carboline/pinoline ratio). Results: Our study revealed the statistically significant results for the treatment efficacy evaluation [the Hamilton Depression Rating Scale scores at the end of the treatment course: (GG) 2.0 (1.0-4.0) and (GA) 5.0 (4.0-7.0), P < 0.001]. Analysis of the results of the pharmacotranscriptomic part of the study did not show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 26.9 (15.0-32.2), (GA) 31.8 (22.7-33.7), P = 0.247. In addition, we evaluated the relationship between the CYP2D6 enzymatic activity (as evaluated by 6-hydroxy-1,2,3,4-tetrahydro-β-carboline/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = -0.243, P = 0.017. Conclusions: The effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of fluvoxamine was demonstrated in a group of 96 patients with depressive disorders comorbid with alcohol use disorder. Competing Interests: The authors have no conflicts of interest to declare. (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.) |
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| المشرفين على المادة: | 0 (MIRN370 microRNA, human) 0 (MicroRNAs) EC 1.14.14.1 (Cytochrome P-450 CYP2D6) O4L1XPO44W (Fluvoxamine) |
| تواريخ الأحداث: | Date Created: 20210612 Date Completed: 20220110 Latest Revision: 20220429 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1097/MJT.0000000000001388 |
| PMID: | 34117140 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1536-3686 |
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| DOI: | 10.1097/MJT.0000000000001388 |