Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia

Julie A. Vignato, S. Banu Gumusoglu, Heather A. Davis, Sabrina M. Scroggins, Wendy S. Hamilton, Debra S. Brandt, Gary L. Pierce, Boyd A. Knosp, Donna A. Santillan, Mark K. Santillan

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential. This retrospective cohort study included clinical data from 9558 SSRI-untreated and 9046 SSRI-treated pregnancies. In a subcohort of 233 pregnancies, early pregnancy (< 20 weeks) maternal plasma copeptin, an inert and stable AVP prosegment secreted 1:1 with AVP, was measured by enzyme-linked immunosorbent assay. Diagnoses and depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) were identified via medical records review. Descriptive, univariate, and multivariate regression analyses were conducted (α = 0.05). SSRI use was associated with decreased preeclampsia after controlling for clinical confounders (depression severity, chronic hypertension, diabetes, body mass index, age) (OR = 0.9 [0.7–1.0], p = 0.05). Moderate-to-severe depression symptoms were associated with significantly higher copeptin secretion than mild-to-no depression symptoms (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001). SSRIs significantly attenuated first trimester plasma copeptin (78 ± 22 users vs. 240 ± 29 ng/ml non-users, p < 0.001). In preeclampsia, SSRI treatment was associated with significantly lower copeptin levels (657 ± 164 vs. 175 ± 134 ng/mL, p = 0.04). Interaction between SSRI treatment and preeclampsia was also significant (p = 0.04). SSRIs may modulate preeclampsia risk and mechanisms, although further studies are needed to investigate the relationships between 5-HT and AVP in depression and preeclampsia. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)701-712
Number of pages12
JournalReproductive Sciences
Issue number2
StatePublished - Feb 2023

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health (T32NR11147, R01HD089940, T32MH01911328), the American Heart Association (18SCG34350001, 15SFRN 23730000, 15 SFRN 23480000, 908921), and an STTI National Research Grant. Data reported in this publication received research support and financial support from the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002537, UL1TR002537-S1). The funders play no role in study design, collection/analysis/interpretation of data, writing of this manuscript, and the decision to submit the manuscript.

Publisher Copyright:
© 2022, The Author(s).


  • Copeptin
  • Depression
  • Preeclampsia
  • Pregnancy
  • Selective serotonin reuptake inhibitors
  • Symptoms


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