|
PM |
IM |
NM |
UM |
Males/Females (N) |
14/21 |
65/108 |
90/152 |
4/4 |
Age (years) (median (IQR)) |
47.0 (38.0-59.0) |
47.0 (33.0-57.0) |
44.5
(33.0-55.75) |
53.5 (46.0-63.0) |
Time from last dose to blood sample (h) (median (IQR)) |
21.3
(15.2-25.1) |
22.0 (13.2-24.5) |
24.0 (14.0-25.5) |
21.5
(20.9-24.1) |
Vortioxetine dose (mg) (median (IQR)) |
10.0 (10.0-20.0) |
10.0
(10.0-20.0) |
13.5 (10.0-20.0) |
15.0 (10.0-16.25) |
Vortioxetine exposure |
Vortioxetine exposure |
Vortioxetine exposure |
Vortioxetine exposure |
Vortioxetine exposure |
Concentration (ng/mL) (median (95% CI)) |
31.6 (15.8-37.9) |
15.5
(13.4-17.6) |
11.2 (10.1-12.1) |
8.1 (4.5-11.3) |
Ratio of medians |
2.8 |
1.4 |
Reference |
0.7 |
Vortioxetine exposure (dose-harmonized to 10 mg/day) |
Vortioxetine exposure (dose-harmonized to 10 mg/day) |
Vortioxetine exposure (dose-harmonized to 10 mg/day) |
Vortioxetine exposure (dose-harmonized to 10 mg/day) |
Vortioxetine exposure (dose-harmonized to 10
mg/day) |
Concentration (ng/mL) (median (95% CI)) |
23.9 (16.9-31.6) |
12.5
(11.3-13.5) |
8.1 (7.6-9.0) |
5.9 (4.0-8.1) |
Ratio of medians |
3.0 |
1.5 |
Reference |
0.7 |
Ln-transformed concentration (mean (95%CI)) |
3.1 (2.9-3.3) |
2.5
(2.4-2.6) |
2.1 (2.1-2.2) |
1.7 (1.5-2.0) |
P valueb
|
<0.001 |
<0.001 |
Reference |
0.21 |
95% confidence interval |
0.65-1.22 |
0.20-0.51 |
Reference |
-0.14-0.99 |
Patients switching to alternative antidepressant treatment
within 3 months |
Patients switching to alternative
antidepressant treatment within 3 months |
Patients switching
to alternative antidepressant treatment within 3 months |
Patients switching to alternative antidepressant treatment
within 3 months |
Patients switching to alternative
antidepressant treatment within 3 months |
Switch / No switch (N) |
6/29 |
8/165 |
6/236 |
2/6 |
P valuec
|
0.001 |
0.28 |
Reference |
0.02 |
Odds-ratio (95% CI) |
8.0 (2.0-32.3) |
1.9 (0.6 – 6.8) |
Reference |
12.7 (1.1-94.9) |
a CYP2D6 phenotype was assigned based on CYP2D6
genotype according to recommendation from the Clinical Pharmacogenomics
Implementation Consortium (CPIC)[4]
b Tukey test (corrected for multiple testing)
comparing the ln-transformed concentrations for each CYP2D6 phenotype
group to the NMs. For the purpose
of statistical comparison, vortioxetine exposure levels were dose
normalized and ln-transformed to restore normal distribution in
accordance with the formula Δln(c)=Ke × t; where c is
concentration, Ke is the elimination rate constant and t
is time.
c Fisher’s exact test comparing the frequency of
switching to an alternative antidepressant for each CYP2D6 phenotype
group to the NMs
|
a CYP2D6 phenotype was assigned based on CYP2D6
genotype according to recommendation from the Clinical Pharmacogenomics
Implementation Consortium (CPIC)[4]
b Tukey test (corrected for multiple testing)
comparing the ln-transformed concentrations for each CYP2D6 phenotype
group to the NMs. For the purpose
of statistical comparison, vortioxetine exposure levels were dose
normalized and ln-transformed to restore normal distribution in
accordance with the formula Δln(c)=Ke × t; where c is
concentration, Ke is the elimination rate constant and t
is time.
c Fisher’s exact test comparing the frequency of
switching to an alternative antidepressant for each CYP2D6 phenotype
group to the NMs
|
a CYP2D6 phenotype was assigned based on CYP2D6
genotype according to recommendation from the Clinical Pharmacogenomics
Implementation Consortium (CPIC)[4]
b Tukey test (corrected for multiple testing)
comparing the ln-transformed concentrations for each CYP2D6 phenotype
group to the NMs. For the purpose
of statistical comparison, vortioxetine exposure levels were dose
normalized and ln-transformed to restore normal distribution in
accordance with the formula Δln(c)=Ke × t; where c is
concentration, Ke is the elimination rate constant and t
is time.
c Fisher’s exact test comparing the frequency of
switching to an alternative antidepressant for each CYP2D6 phenotype
group to the NMs
|
a CYP2D6 phenotype was assigned based on CYP2D6
genotype according to recommendation from the Clinical Pharmacogenomics
Implementation Consortium (CPIC)[4]
b Tukey test (corrected for multiple testing)
comparing the ln-transformed concentrations for each CYP2D6 phenotype
group to the NMs. For the purpose
of statistical comparison, vortioxetine exposure levels were dose
normalized and ln-transformed to restore normal distribution in
accordance with the formula Δln(c)=Ke × t; where c is
concentration, Ke is the elimination rate constant and t
is time.
c Fisher’s exact test comparing the frequency of
switching to an alternative antidepressant for each CYP2D6 phenotype
group to the NMs
|
a CYP2D6 phenotype was assigned based on CYP2D6
genotype according to recommendation from the Clinical Pharmacogenomics
Implementation Consortium (CPIC)[4]
b Tukey test (corrected for multiple testing)
comparing the ln-transformed concentrations for each CYP2D6 phenotype
group to the NMs. For the purpose
of statistical comparison, vortioxetine exposure levels were dose
normalized and ln-transformed to restore normal distribution in
accordance with the formula Δln(c)=Ke × t; where c is
concentration, Ke is the elimination rate constant and t
is time.
c Fisher’s exact test comparing the frequency of
switching to an alternative antidepressant for each CYP2D6 phenotype
group to the NMs
|