Association between CYP2D6 genotype and vortioxetine exposure and
therapeutic failure - a retrospective, cohort study
Abstract
The antidepressant vortioxetine is primarily metabolised by the
polymorphic enzyme CYP2D6. The objective of this study was to
investigate the effect of CYP2D6 genotype on exposure and therapeutic
failure of vortioxetine. The analysis included data from
CYP2D6-genotyped patients (N=458) on vortioxetine treatment from a
Norwegian therapeutic drug monitoring database. Compared with CYP2D6
normal metabolizers (NMs; N=242), vortioxetine exposure was 3.0-fold
(p<0.001) increased in poor metabolizers (PMs; N=35), 1.5-fold
(p<0.001) increased in intermediate metabolizers (IMs; N=173),
and not significantly changed (p=0.21) in ultra-rapid metabolizers (UMs;
N=8). Compared with NMs, treatment switch from vortioxetine to
alternative antidepressants was 8.0-fold (95%CI: 2.0-32.3, p=0.001)
more frequent among PMs and 12.7-fold (95%CI: 1.1-94.9, p=0.02) more
frequent among the CYP2D6 UMs. In conclusion, CYP2D6 genotype was
associated with significant changes in vortioxetine exposure and may
also be associated with risk of therapeutic failure.