RESULTS
516 CYP2D6 -genotyped patients on vortioxetine treatment were
identified in the TDM database. Among these, 29 were excluded due to
concomitant use of CYP inhibitors/inducers, 8 due to serum concentration
measurements of vortioxetine being below the lower limit of
quantification, and 21 patients lacking information about the prescribed
vortioxetine dose. Thus, a total of 458 patients were included in the
analysis.
The frequencies of CYP2D6 genotype-predicted PMs, IMs, NMs and
UMs in the population were 7.6%, 37.8%, 52.8% and 1.7%,
respectively, and all the CYP2D6 variant alleles were in
Hardy-Weinberg equilibrium. There were no significant differences in
patient demographics or time intervals between the last vortioxetine
dose and TDM blood sampling between the CYP2D6 phenotype groups (seeTable 1 ). The median vortioxetine dose administered in the PM
and IM groups were lower than those in the NM and UM groups, but the
differences were not statistically significant.
The median vortioxetine exposure, measured by dose-harmonized
concentration, was highest among the CYP2D6 PMs (23.9 ng/mL), followed
by the IMs (12.5 ng/mL), NMs (8.1 ng/mL), and lowest for the UMs (5.9
ng/mL) (see Figure 1 ). The CYP2D6 PMs and IMs exhibited
significantly higher vortioxetine exposures (P<0.001) compared
to NMs with ratios of medians being 3.0 and 1.5, respectively. No
significant difference in vortioxetine exposure was found between the
CYP2D6 UMs and NMs (P=0.21).
In addition to the exposure differences, the frequency of patients
switching from vortioxetine to an alternative antidepressant during the
course of three-month follow-up was significantly higher among PMs
compared to NMs (P=0.001, odds ratio (OR) 8.0, 95% CI=2.0-32.2). CYP2D6
UMs also showed a significantly higher frequency of treatment switch
compared to NMs (P=0.02, OR 12.7, 95% CI=1.1-94.9), while no
significant difference was found between the IMs and NMs (P=0.28, OR
1.9, 95% CI=0.6-6.8).