Hypertension in pregnancy is mostly defined as a diastolic blood pressure of 90 mm Hg or greater or a systolic pressure at or above 140 mm Hg.  Preeclampsia is defined as the event of hypertension together with proteinuria or edema while pregnant, generally within the second half of gestation.  Preeclampsia is more common in women who haven’t carried a previous pregnancy beyond 20 weeks and in women at either extreme of their reproductive years.

Exactly what causes preeclampsia isn’t fully understood. Because serotonin plays a job in vascular function and the regulation of blood pressure, some have questioned whether using serotonin reuptake inhibitor (SRI) antidepressants may affect a girl’s risk for hypertension or preeclampsia.  While several observational studies have indicated an increased risk of hypertension and/or preeclampsia in women taking SRIs while pregnant, this finding isn’t consistent, and most of those studies have been small and haven’t been in a position to account for potential confounding aspects.   

Meta-Evaluation: SSRIs and Risk for Hypertension and Preeclampsia

To raised estimate the chance of gestational hypertension and preeclampsia in women taking SSRI antidepressants while pregnant, Gumusoglu and colleagues conducted a meta-analysis of observational cohort or population studies of girls who used SSRIs while pregnant, choosing studies that specifically addressed the query of whether gestational SSRI use modulates risk of preeclampsia and/or gestational hypertension.  The ultimate evaluation included nine studies published between 2009 and 2020, including roughly 40,000 SSRI-exposed pregnancies.

Among the many nine included studies, two evaluated risk of gestational hypertension and 7 evaluated risk of preeclampsia.  Of the nine studies assessed, three reported a statistically significant increase in risk of gestational hypertension or preeclampsia in SSRI-exposed pregnancies. 4 studies reported a non-significant increase in risk of preeclampsia or gestational hypertension with SSRI use while pregnant. The pooled relative risk (RR) of gestational hypertension or preeclampsia was 1.43 (95 % CI: 1.15–1.78, P < 0.001).

While this meta-analysis does show a small, statistically significant association between prenatal SSRI exposure and risk of gestational hypertension or preeclampsia, the authors note some vital limitations of this meta-analysis.  Most significantly, a lot of the studies included within the meta-analysis did not account for anxiety/depression severity, SSRI dose, and/or other well-defined preeclampsia risk aspects (e.g., obesity, diabetes, smoking, race).  Essentially the most common limitation of the included studies was the failure to account for anxiety/depression severity within the mother, which can independently drive risk for gestational hypertension and/or preeclampsia.

The Link Between Depression and Preeclampsia

Gumusoglu and colleagues note that girls who use SSRIs in pregnancy can have increased risk for preeclampsia just because additionally they have more severe depressive illness, which has been identified as an independent preeclampsia risk think about other studies (Qiu et al, 2007).  Actually, they note that when specific dimensions of maternal mental health are accounted for, the relative risk for preeclampsia amongst SSRI users isn’t significant, as observed within the study from 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 doesn’t significantly increase preeclampsia risk (Lupattelli et al, 2017).  Making the evaluation of this association much more complicated is the proven fact that several preeclampsia risk aspects (including obesity, metabolic syndrome, and heart problems) are more common in women with depression.  

Is it Possible that SSRIs May Actually Decrease Risk for Preeclampsia

While this meta-analysis does show a small, statistically significant association between prenatal SSRI exposure and risk of gestational hypertension or preeclampsia, there are vital limitations to contemplate.  Most studies fail to account for well-defined preeclampsia risk aspects (e.g., obesity, diabetes, smoking, race).  Moreover, there’s increasing evidence to point that anxiety and/or depression within the mother may independently drive risk for gestational hypertension and/or preeclampsia.

It’s biologically plausible that SRIs may very well decrease risk for preeclampsia.  Each depression and preeclampsia are related to dysregulation of serotonergic neurotransmitter systems; thus, it’s plausible that medications, resembling SRI antidepressants, that improve serotonergic regulation can also help to diminish depressive symptoms, in addition to decrease vulnerability to preeclampsia.  In an upcoming post, we’ll discuss a preliminary study that supports this hypothesis.  Stay tuned. 

While future studies will help to make clear the complex interaction between depression, SSRI treatment and pre-eclampsia, the data we’ve got so far is reassuring.  If there’s a risk of preeclampsia related to SSRI treatment, the chance appears to be relatively small.  Nevertheless, there’s considerable data to point that risk of preeclampsia is higher in women with depressive illness (even within the absence of treatment with an SSRI) and should be affected by other co-occurring risk aspects, resembling obesity, chronic hypertension, diabetes mellitus, and smoking.

Ruta Nonacs, MD PhD

References

Lupattelli A, Wood M, Lapane K, Spigset O, Nordeng H. Risk of preeclampsia after gestational exposure to selective serotonin reuptake inhibitors and other antidepressants: A study from The Norwegian Mother and Child Cohort Study. Pharmacoepidemiol Drug Saf. 2017 Oct; 26(10):1266-1276. 

Palmsten K, Setoguchi S, Margulis AV, Patrick AR, Hernández-Díaz S. Elevated risk of preeclampsia in pregnant women with depression: depression or antidepressants? Am J Epidemiol. 2012 May 15;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 Womens Health 2007; 7:15.