Effect of Genetic Polymorphism of the CYP2D6 Gene on the Efficacy and Safety of Fluvoxamine in Major Depressive Disorder.
Am J Ther
; 29(1): e26-e33, 2021 Jun 03.
Article
en En
| MEDLINE
| ID: mdl-34117140
ABSTRACT
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. STUDYDESIGN:
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 ANDOUTCOMES:
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-ß-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-ß-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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Trastorno Depresivo Mayor
Límite:
Humans
/
Male
Idioma:
En
Revista:
Am J Ther
Asunto de la revista:
TERAPEUTICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Rusia