Effect of Genetic Polymorphism of the CYP2D6 Gene on the Efficacy and Safety of Fluvoxamine in Major Depressive Disorder.

American Journal of Therapeutics
Michael ZastrozhinDmitry Sychev

Abstract

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. Efficacy and safety of fluvoxamine depend on the polymorphism of CYP2D6 gene in patients with major depressive disorder. 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. 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-carbolin...Continue Reading

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