Hypertension in pregnancy is usually defined as a diastolic blood pressure of 90 mmHg or more or a systolic blood pressure of more than 140 mmHg. Preeclampsia is defined as the development of hypertension with proteinuria or edema during pregnancy, mostly in the second half of pregnancy. Preeclampsia is more common in women who have not had a previous pregnancy for more than 20 weeks, as well as in women of childbearing age.
What exactly causes preeclampsia is not entirely clear. Because serotonin plays a role in blood vessel function and blood pressure regulation, some have questioned whether the use of serotonin reuptake inhibitor (SRI) antidepressants may affect the risk of hypertension or preeclampsia. Although several observational studies have shown an increased risk of hypertension and/or preeclampsia in women taking SRF during pregnancy, this finding is inconsistent, and most of these studies were small and failed to account for potential confounding factors.
Meta-analysis. SSRIs and risk of hypertension and preeclampsia
To better assess the risk of gestational hypertension and preeclampsia in women taking SSRI antidepressants during pregnancy, Gumushoglu and colleagues conducted a meta-analysis observational cohort or population studies of women using SSRIs during pregnancy, selecting studies that specifically addressed whether SSRI use during pregnancy modulates the risk of preeclampsia and/or gestational hypertension. The final analysis included nine studies published between 2009 and 2020, inclusive approximately 40,000 SSRI-exposed pregnancies.
Of the nine included studies, two assessed the risk of gestational hypertension and seven assessed the risk of preeclampsia. Three of the nine studies evaluated reported a statistically significant increased risk of gestational hypertension or preeclampsia in SSRI-exposed pregnancies. Four studies reported a nonsignificant increased risk of preeclampsia or gestational hypertension with SSRI use during pregnancy. The pooled relative risk (RR) of gestational hypertension or preeclampsia was 1.43 (95 % CI: 1.15–1.78, P < 0.001).
Although this meta-analysis shows a small, statistically significant association between prenatal SSRI exposure and the risk of gestational hypertension or preeclampsia, the authors note some important limitations of this meta-analysis. The most important thing is Most studies included in the meta-analysis failed to account for severity of anxiety/depression, SSRI dose, and/or other well-defined risk factors for preeclampsia (eg, obesity, diabetes, smoking, race). The most common limitation of the included studies was the failure to measure the severity of maternal anxiety/depression, which may independently increase the risk of gestational hypertension and/or preeclampsia.
The relationship between depression and preeclampsia
Gumushoglu and colleagues note that women who use SSRIs during pregnancy may be at risk for preeclampsia simply because they also have more severe depressive illness, which has been identified as an independent risk factor for preeclampsia in other studies (Qiu et al. al, 2007). In fact, they note that when specific measures of maternal mental health were taken into account, the relative risk of preeclampsia among SSRI users was not significant, as observed in the study by Palmsten and colleagues (RR 1.16, 95% CI 0.92–1.45). Similarly, after accounting for lifetime major depressive episodes, SSRI use in early and mid-pregnancy did not significantly increase the risk of preeclampsia (Lupatelli et al., 2017). Further complicating the analysis of this association is the fact that several preeclampsia risk factors (including obesity, metabolic syndrome, and cardiovascular disease) are more common in women with depression.
Is it possible that SSRIs may actually reduce the risk of pre-eclampsia?
Although this meta-analysis shows a small, statistically significant association between prenatal SSRI exposure and risk of gestational hypertension or preeclampsia, there are important limitations to consider. Majority studies fail to account for well-defined risk factors for preeclampsia (eg, obesity, diabetes, smoking, race). Furthermore, there is increasing evidence that maternal anxiety and/or depression may independently increase the risk of gestational hypertension and/or preeclampsia.
It is biologically plausible that SRIs may actually reduce the risk of preeclampsia. Both depression and preeclampsia are associated with dysregulation of serotonergic neurotransmitter systems; Thus, it is likely that drugs such as SRI antidepressants that improve serotonergic regulation may also help reduce depressive symptoms as well as reduce vulnerability to preeclampsia. In an upcoming post, we’ll discuss a preliminary study supporting this hypothesis. Stay with us.
Although future studies will help clarify the complex interaction between depression, SSRI treatment, and preeclampsia, the information we have so far is encouraging. If there is a risk of preeclampsia associated with SSRI treatment, the risk appears to be relatively small. However, there is considerable evidence that the risk of preeclampsia is higher in women with depressive illness (even in the absence of SSRI treatment) and may be influenced by other risk factors such as obesity, chronic hypertension, diabetes. mellitus, and smoking.
Ruta Nonacs, MD PhD
Lupattelli A, Wood M, Lapane K, Spigset O, Nordeng H. Risk of preeclampsia after exposure to selective serotonin reuptake inhibitors and other antidepressants during pregnancy. Pharmacoepidemiol Drug Saf. October 2017 26 (10). 1266-1276
Palmsten K, Setoguchi S, Margulies AV, Patrick AR, Hernandez-Diaz S. Increased risk of preeclampsia in pregnant women with depression. depression or antidepressants? Am J Epidemiol. May 15, 2012; 175 (10). 988-97.
Qiu C, Sanchez SE, Lam N, Garcia P, Williams MA. Associations of depression and depressive symptoms with preeclampsia. results from a Peruvian case-control study. BMC Women’s Health 2007; 7:15