Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder

• Published in: Canadian journal of physiology and pharmacology Vol. 97; no. 8; pp. 781 - 785
• Main Authors: Zastrozhin, M.S, Skryabin, V.Y, Smirnov, V.V, Grishina, E.A, Ryzhikova, K.A, Chumakov, E.M, Bryun, E.A, Sychev, D.A
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.08.2019; Canadian Science Publishing NRC Research Press
• Subjects: Adult; Alcohol use; Alcoholic beverages; Alcoholism - drug therapy; Alcoholism - enzymology; Alcoholism - epidemiology; Alcoholism - genetics; Analysis; Antianxiety agents; Care and treatment; Comorbidity; Correlation coefficients; CYP2D6; CYP2D6 protein; Cytochrome P-450; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 - metabolism; Cytochrome P450; Depression, Mental; Depressive Disorder - drug therapy; Depressive Disorder - enzymology; Depressive Disorder - epidemiology; Depressive Disorder - genetics; Drinking of alcoholic beverages; Enzymes; Female; Genotype; Genotypes; Genotyping; High performance liquid chromatography; Humans; Hybridization; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Medical research; Medicine, Experimental; Mental depression; Metabolic rate; Metabolites; mirtazapine; Mirtazapine - adverse effects; Mirtazapine - pharmacology; Mirtazapine - therapeutic use; médecine personnalisée; personalized medicine; Pharmacogenetics; pharmacogenomics; pharmacogénomique; Pharmacology; Physiology; Pinoline; Polymerase chain reaction; Polymorphism, Genetic; Precision medicine; Psychological aspects; Safety; Statistical analysis; Russia; mirtazapine; pharmacogenomics; CYP2D6; pharmacogénomique; pinoline; médecine personnalisée; personalized medicine
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2019-0177

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite — pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography – mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = −0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.