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

Abstract

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.

Polymorphism 3435c> t of the ABCB1 gene (rs1045642) does not affect the mirtazapine efficiency and safety profile in patients with depressive disorders comorbid with alcohol use disorder

“…Таким образом, исходя из полученных результатов о том, что полиморфизм гена не оказывает влияния на эффективность и безопасность терапии миртазапином у пациентов с депрессивными расстройствами, коморбидными с алкогольной зависимостью, возможно предположить, что перед назначением миртазапина пациентам данной категории учитывать результаты генотипирования по локусам данного гена не нужно. В то же время при назначении миртазапина необходимо принимать во внимание полиморфизм гена CYP2D6, так как показано, что его полиморфизм может оказывать влияние на профиль эффективности и безопасности миртазапина у пациентов данной категории [14][15][16].…”

Pharmacogenomics for the efficacy and side effects of antihistamines

“…72 The most common allelic variants associated with the poor metabolizer phenotype are CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*6. 72 People who are poor metabolizers are more likely to be affected by poor substrate metabolism. CYP2D6 is involved in the main metabolic pathway for many sedative drugs in the central nervous system.…”

Pharmacogenomics for Primary Care: An Overview

“…In the case of both fluvoxamine and paroxetine, the CPIC guideline highlights the possibility of ADRs potentiated by higher plasma concentrations in CYP2D6 PMs [ 33 ]. Some evidence exists to correlate increased ADRs with mirtazapine in CYP2D6 IM and PM patients [ 34 , 35 ]. However, at this time, no clinically actionable PGx recommendation exists for mirtazapine.…”