INTRODUCTION
Numerous psychotropic medications are metabolized by the polymorphic CYP2D6 enzyme. The CYP2D6 gene encoding the enzyme is highly polymorphic, which in turn causes substantial interindividual variability in enzyme activity. Based on their CYP2D6 genotype, patients are commonly categorized into four phenotype groups: (1) poor metabolizer (PM) exhibit complete absence of active CYP2D6 enzyme, (2) intermediate metabolizer (IM) exhibit reduced CYP2D6 metabolic capacity, (3) normal metabolizer (NM) exhibit normal CYP2D6 metabolic and (4) ultra-rapid metabolizer (UM) exhibit increased CYP2D6 metabolic capacity. The frequency of phenotypes in the population varies across ethnicities with 3-10% being categorized as PMs, 15-40% as IMs, 1-9% as UMs and the remaining as NMs (40-85%) [1].
Vortioxetine is a novel antidepressant, indicated for the treatment of major depressive disorder (MDD). Clinical studies have demonstrated antidepressant efficacy and a favourable tolerability profile of vortioxetine in the dose range 5-20 mg/day. However, as for other antidepressants, there is substantial interindividual variability in clinical response [2]. Vortioxetine is metabolized by several CYP isoforms, with CYP2D6 accounting for approximately half of the total clearance [3]. The objective of this study was to investigate the effect of CYP2D6 genotype on systemic vortioxetine exposure and therapeutic failure of vortioxetine in a naturalistic setting using data from therapeutic drug monitoring (TDM).