Optimizing Medication Management for Mothers With Depression

The overarching goal of this The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) funded U54 Obstetric-Fetal Pharmacology Research Center study is to develop evidence to construct guidelines for the optimal use of selective serotonin reuptake inhibitor (SSRI) antidepressants in pregnant women. The progressive changes in plasma SSRI and metabolite concentrations across pregnancy and after birth will be determined in an observational study. Serial evaluations of depressive and anxiety symptoms and side effects will be obtained to evaluate their association with plasma concentrations at monthly intervals during pregnancy and twice post-birth. To assess the subjects' metabolic phenotypes, subjects have the option to receive a probe drug cocktail, which will be given to evaluate the activities of enzymes involved in antidepressant metabolism during the third trimester (when activity change is maximal) compared to the non-pregnant state after birth. Additionally, the study team will investigate the impact of genomic variability on inter-individual differences in SSRI dosing, plasma concentrations and pharmacodynamics during pregnancy, with a focus on genes involved in the metabolism and elimination of SSRIs, drug transporters responsible for SSRI access to the central nervous system, and genes encoding critical SSRI targets involved in therapeutic efficacy. Finally, the study team will determine the maternal-fetal plasma concentrations and pharmacogenetic characteristics associated with neonatal SSRI abstinence syndrome. Maternal and fetal genotypes will be assessed for their relationship to SSRI drug concentrations and neonatal abstinence syndrome.