Impact of combined CYP2C19/CYP2B6 phenotypes on sertraline dose-normalized concentration and antidepressant switching incidence: A retrospective cohort study in Chinese Han population.

CYP2C19

Sertraline is metabolised mainly by the polymorphic cytochromes CYP2C19 and CYP2B6; the combination of both metabolizer phenotypes modulates dose-normalized serum concentration.

This retrospective Chinese Han cohort analysed 1,070 patients and 1,414 sertraline serum measurements, classified by CYP2C19 and CYP2B6 metabolizer phenotypes into 16 combined groups, with normal metabolizers for both genes as the reference. Eight groups had significantly higher dose-normalized concentrations than the reference, the largest difference in CYP2C19 poor / CYP2B6 intermediate metabolizers (fold change 2.11; 95% CI 1.84-2.42; adjusted P < 0.001) and the smallest in CYP2C19 normal / CYP2B6 intermediate metabolizers (fold change 1.15; 95% CI 1.06-1.26). The combined model fitted better than the CYP2C19-only model (likelihood ratio test, χ² = 28.6; P < 0.001). Antidepressant switching within one year of the last monitoring assessment occurred in 19.9% of patients overall, and in up to 34.3% of CYP2C19 poor / CYP2B6 intermediate metabolizers (OR 3.33; 95% CI 1.50-7.41).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value of this work is that it goes beyond concentration by linking the combined phenotype to a pragmatic endpoint, antidepressant switching within one year. The improvement in model fit from adding CYP2B6 is statistically clear, but the smallest concentration differences (fold change 1.15) carry no obvious dosing implication. The retrospective design and single-ethnicity setting call for prospective validation before any recommendation for combined genotyping.

Analysis by Dr Thibaut Benquey