Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1280-1290 |
| Number of pages | 11 |
| Journal | Clinical pharmacology and therapeutics |
| Volume | 112 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2022 |
Funding
This study, Optimizing Medication Management for Mothers with Depression (OPTIMOM, NICHD 1U54HD085601-01, Clinical Trials.gov ID NCT02519790, PIs: KL Wisner, C Stika, A George), was supported by The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; U54HD047891, U54HD047905, and U54HD085601), UL1TR001439 from the National Institute of Health (NIH), the Obstetric-Fetal Pharmacology Research Center (OPRC), the Asher Center for the Study and Treatment of Depressive Disorders, the Center for Pharmacogenomics, and the Northwestern University Feinberg School of Medicine. The research reported in this publication was supported, in part, by the NIH's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. This work was also supported by the Mary Beth Donnelley Clinical Pharmacology Core Facility at Northwestern University and NIH S10 OD021786. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All study data presented in this paper were collected and processed with the support of this funding. The study team acknowledges the contributions of our participants and research team who conducted this study. We acknowledge the support of our program officer, Zhaoxia Ren, MD, PhD; research coordinators, Emily Pinheiro, Kelly O'Shea, MPH, Minaz Cattan, MD, Elizabeth Torres, BS, and Syeda Fatima (Northwestern University); Dawn Fischer, BSN (University of Pittsburgh), Elizabeth Welch, RN (University of Texas Medical Branch); statistical analyst Amy Yang, MS; clinical evaluators Dorothy Sit, MD, and Crystal Clark, MD, MSc; pharmacogenetic analyst Tatiana Abramova, MS; Mary Beth Donnelley Clinical Pharmacology Core Facility director, Ben Owen, PhD, and mass spectrometry specialist, Arsen Gaisin. We also acknowledge the contributions of Alpa Shah, MD, Veera Kommisetti, MD, Trista Barlow, RN, Sandra Freeman, Tammy Gault, and Hope Florence at Marshfield Clinic Health System, Wisconsin. A.L.G. Jr. receives grant support from Tevard Biosciences, Praxis Precision Medicines, and Neurocrine Biosciences for unrelated work. A.L.G. consults for Merck, Tevard Biosciences, Praxis Precision Medicines, and Neurocrine Biosciences for unrelated work. All other authors declared no competing interests for this work. This study, (OPTIMOM, NICHD 1U54HD085601‐01, Clinical Trials.gov ID NCT02519790, PIs: KL Wisner, C Stika, A George), was supported by The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; U54HD047891, U54HD047905, and U54HD085601), UL1TR001439 from the National Institute of Health (NIH), the Obstetric‐Fetal Pharmacology Research Center (OPRC), the Asher Center for the Study and Treatment of Depressive Disorders, the Center for Pharmacogenomics, and the Northwestern University Feinberg School of Medicine. The research reported in this publication was supported, in part, by the NIH's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. This work was also supported by the Mary Beth Donnelley Clinical Pharmacology Core Facility at Northwestern University and NIH S10 OD021786. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All study data presented in this paper were collected and processed with the support of this funding. Optimizing Medication Management for Mothers with Depression
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
