Association Between CYP2D6 Genotypes and Serum Concentrations of Mirtazapine and Mianserin

Abstract

The aim of the present study was to investigate the effect of CYP2D6 genotypes on mirtazapine and mianserin serum concentrations. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of CYP2D6 genotype, age and sex on mirtazapine and mianserin concentration-to-dose (C/D) ratio. The study included 2315 mirtazapine patients and 474 mianserin patients who were assigned to the genotype-predicted phenotype groups of CYP2D6 poor metabolizers (PMs), intermediate metabolizers (IMs), normal metabolizers (NMs) and ultrarapid metabolizers (UMs). Multiple linear regression analysis revealed 18% and 14% higher mirtazapine C/D ratio in CYP2D6 PMs and IMs, respectively, compared with NMs (p ≤ 0.004). For mianserin, the C/D ratio was 80% and 45% higher in PMs and IMs, respectively, compared with NMs (p < 0.001). The C/D ratio in UMs did not differ from NMs for either drug (p ≥ 0.3). In conclusion, CYP2D6 genotype was only associated with a minor change in mirtazapine serum concentration. The association between CYP2D6 genotype and mianserin serum concentration was greater, with 80% higher mianserin C/D ratio in CYP2D6 PMs compared with NMs.

Keywords: CYP2D6; genotype; mianserin; mirtazapine; pharmacogenetics.