genotype-dependent effects of smoking on mirtazapine serum concentrations.

INTRODUCTION

Psychopharmacotherapy with mirtazapine is commonplace. Lower serum concentrations of mirtazapine were reported in smokers due to induction. However, no previous study that investigated genetics and mirtazapine treatment considered inducing parameters.

AIM

We aimed to investigate the association of variants, mirtazapine serum concentration, and treatment outcome, considering the smoking status of the patients.

METHODS

Two depression cohorts were investigated for the association between serum concentration and treatment response of mirtazapine and -163C>A (rs762551) and -3860G>A (rs2069514) genotype groups, also considering smoking status, sex, and age of the patients. In total, 124 patients (82 non-smokers and 42 smokers) were eligible for the analyses.

RESULTS

Dose-corrected serum concentration (CD) of mirtazapine was associated with smoking status, sex, and age, with lower CD in smokers, females, and older patients. Considering non-smokers and genotype-grouped smokers, CD of mirtazapine in normal metabolizer smokers ( = 6) did not differ from CD of non-smokers. By contrast, smokers carrying the *1A/*1F and *1F/*1F genotype groups showed 34.4% and 33.4% lower mirtazapine CD compared to non-smokers.

DISCUSSION

As yet, for clinical practice, it may be more relevant to focus on smoking status than on the gene variants. Considering the relevant impact of smoking on the mirtazapine CD, physicians should monitor an increase in side effects due to the expected increase in mirtazapine serum concentrations. In these cases, measurement of mirtazapine CD and/or subsequent dosage reduction is recommended. The clinical relevance of genotyping prior to treatment with drugs metabolized by needs further investigation.