Changes in Sertraline Plasma Concentrations Across Pregnancy and Postpartum

Major depressive disorder (MDD) is a common disorder in pregnancy. Although sertraline is the most frequently prescribed antidepressant for pregnant people in the United States, limited information about its pharmacokinetics in pregnancy is available. Our objectives were to characterize plasma sertraline concentration to dose (C/D) ratios across pregnancy and postpartum and investigate the effect of pharmacogenetic variability on sertraline elimination. We performed a prospective observational cohort study in people with a singleton pregnancy ≤ 18 weeks gestation and a lifetime diagnosis of MDD at the 3 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)-funded Obstetrical-Fetal Pharmacology Research Center sites. Subjects (N = 47) were receiving maintenance sertraline therapy and chose to continue it during pregnancy. Blood samples were obtained 24-hours postdose every 4 weeks across pregnancy and twice postpartum for measurement of plasma concentrations of sertraline and desmethylsertraline. Overall mean sertraline C/D ratios were decreased at study onset and remained consistently low until after delivery. During the last 4 weeks of pregnancy the mean sertraline C/D ratio (95% confidence interval (CI)), 0.25 (95% CI, 0.19, 0.3) ng/mL/dose (mg/day), was smaller than the mean ratio at ≥ 8 weeks after delivery, 0.32 (95% CI, 0.27, 0.37) ng/mL/dose (mg/day), a 22% difference. Mean sertraline/desmethylsertraline ratios were highest after birth, which confirmed increased sertraline elimination during pregnancy. Sertraline C/D ratios in participants with functional CYP2C19 activity did not change significantly during pregnancy, whereas ratios in participants with poor or intermediate CYP2C19 activity decreased by 51%. Exploratory pharmacogenomic analysis indicated that pregnant people with poor or intermediate CYP2C19 activity are at risk for subtherapeutic sertraline concentrations during pregnancy.