Preeclampsia is a complication of pregnancy characterized by high blood pressure and liver and kidney function abnormalities.  Preeclampsia occurs in approximately 5-8% of pregnancies and is a leading cause of maternal and fetal morbidity and mortality. Risk factors for preeclampsia include preeclampsia during a previous pregnancy, first pregnancy, multiple gestation, maternal age over 40, obesity, and certain underlying medical conditions including chronic hypertension, diabetes, and kidney disease.

Exactly what causes preeclampsia is not fully understood. Because serotonin plays a role in vascular function and the regulation of blood pressure, some have questioned whether the use of serotonin reuptake inhibitor (SRI) antidepressants may affect a woman’s risk for preeclampsia.  While several studies have indicated an increased risk of preeclampsia in women taking SRIs during pregnancy, this finding is not consistent, and most of these studies have been small and have not been able to account for potential confounding factors.   

A recent meta-analysis including 400,000 SSRI-exposed women did show a small, statistically significant association between prenatal SSRI exposure and risk of preeclampsia.  However, the authors noted some important limitations of this meta-analysis.  Most importantly, most of the studies included in the meta-analysis failed to account for anxiety/depression severity, SSRI dose, and/or other well-defined preeclampsia risk factors (e.g., obesity, diabetes, smoking, race).  The most common limitation of the included studies was the failure to account for anxiety/depression severity in the mother, which may independently drive risk for preeclampsia.

Taking a Closer Look at SRIs and Preeclampsia

It is biologically plausible that SRIs may actually decrease risk for preeclampsia.  Both depression and preeclampsia are associated with dysregulation of serotonergic neurotransmitter systems; thus, it is plausible that medications, such as SRI antidepressants, that improve serotonergic regulation may also help to decrease depressive symptoms, as well as decrease vulnerability to preeclampsia.  

To further explore this possibility,  Vignato and colleagues assessed clinical data from a retrospective study of 9558 SSRI-untreated and 9046 SSRI-treated pregnancies.  Psychiatric diagnoses were identified using a review of medical records, and depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9).  They observed that SSRI use during pregnancy was associated with decreased risk of preeclampsia after controlling for clinical confounders, including depression severity, history of chronic hypertension, diabetes, body mass index, and age (odds ratio, OR = 0.9 [95% CI 0.7-1.0], p = 0.05).

Going one step further, this study also examined how depression and SSRI treatment may affect risk for preeclampsia by examining copeptin levels.  Copeptin is a peptide co-secreted (at a 1:1 ratio) with arginine vasopressin (AVP) in response to hemodynamic or osmotic stimuli.  In patients with preeclampsia, increased AVP secretion stimulates an increase in blood pressure.  Copeptin is easier to measure than AVP, and previous studies have demonstrated that copeptin levels are a reliable predictor of preeclampsia risk.  

In a subset of 233 pregnancies, early pregnancy (< 20 weeks) levels of copeptin were measured.  Compared to women with mild or no depression, women with moderate to severe depressive symptoms produced significantly higher levels of copeptin (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001).  Treatment with SSRIs significantly reduced first trimester copeptin levels (78 ± 22 in users vs. 240 ± 29 ng/ml in non-users, p < 0.001). 

Looking specifically at women with moderate-to-severe depressive symptoms who were taking SSRIs, copeptin levels were much lower in SSRI-treated women than in women with moderate-to-severe depressive symptoms who were untreated (181?±?64 ng/mL [n?=?10] vs. 657?±?164 [n?=?10], p?=?0.02). 

Clinical Implications

Based on the findings of this study, it is possible that SSRIs may actually decrease preeclampsia risk, whereas depressive symptoms, especially when more severe, may actually increase risk for preeclampsia.  

While future studies will help to clarify the complex interaction between depression, SSRI treatment and pre-eclampsia, the information we have thus far is reassuring.  If there is a risk of preeclampsia associated with SSRI treatment, the risk appears to be relatively small.  However, there is considerable data to indicate that risk of preeclampsia is higher in women with depressive illness (even in the absence of treatment with an SSRI) and may be affected by other co-occurring risk factors, such as obesity, chronic hypertension, diabetes mellitus, and smoking.

Ruta Nonacs, MD PhD



Gumusoglu SB, Schickling BM, Vignato JA, Santillan DA, Santillan MK. Selective serotonin reuptake inhibitors and preeclampsia: A quality assessment and meta-analysis. Pregnancy Hypertens. 2022 Dec; 30:36-43. 

Vignato JA, Gumusoglu SB, Davis HA, Scroggins SM, Hamilton WS, Brandt DS, Pierce GL, Knosp BA, Santillan DA, Santillan MK. Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia. Reprod Sci. 2022 Aug 19. 


Related Posts