Impact of <i>CYP2C19</i> Genotype on Sertraline and Escitalopram Exposure and Antidepressant Switching Rate: A Retrospective Cohort Study of Chinese Han Patients

Sertraline and escitalopram, commonly used antidepressants in clinical practice, are metabolized by the polymorphic CYP2C19 enzyme. In a large-scale Chinese Han cohort, this study comprehensively examines the influence of CYP2C19 genotype on sertraline and escitalopram exposure, while also evaluating genotype-associated antidepressant switching rates. A total of 525 serum concentration measurements of sertraline in 415 patients and 355 serum concentration measurements of escitalopram in 294 patients were retrospectively included from the therapeutic drug monitoring database of the First Hospital of Hebei Medical University. Patients were categorized into four subgroups based on CYP2C19 genotype: Normal metabolizers (NMs), Rapid metabolizers (RMs), Intermediate metabolizers (IMs), and Poor metabolizers (PMs). Differences in sertraline and escitalopram exposure and antidepressant switching rates were compared between the subgroups, with CYP2C19 NMs set as reference. Compared with the CYP2C19 NMs group, sertraline serum concentrations were significantly increased 2-fold and 1.3-fold in the CYP2C19 PMs and CYP2C19 IMs groups, respectively, and escitalopram serum concentrations were significantly increased 2-fold and 1.2-fold in the CYP2C19 PMs and CYP2C19 IMs groups, respectively. Compared to the CYP2C19 NMs group, the antidepressant switching rate of sertraline in the CYP2C19 PMs and CYP2C19 IMs groups was significantly increased 5.8-fold and 2.8-fold; the antidepressant switching rate of escitalopram in the CYP2C19 RMs, CYP2C19 PMs, and CYP2C19 IMs groups was increased 13.1-fold, 3.7-fold, and 2.4-fold, respectively. The CYP2C19 genotype exerts a substantial influence on the exposure and the antidepressant switching rate of sertraline and escitalopram. CYP2C19 genotyping prior to administering drugs is clinically beneficial.