Patient characteristics (N = 516) CYP2D6 Phenotypea CYP2D6 Phenotypea CYP2D6 Phenotypea CYP2D6 Phenotypea
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