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).