Abstract
ObjectiveThe association between antidepressants and preeclampsia has been inconsistently reported. Given the compound-specific variable affinity for different transporters/receptors, their effect on preeclampsia risk could differ. Our study examined the risk of preeclampsia (and its subtypes) following exposure to different classes of antidepressants, also accounting for specific transporters/receptors targeted by antidepressants. MethodsWe conducted a cohort study, combining data from the Netherlands Perinatal Registry and the PHARMO Database Network. Exposure to antidepressants was examined from conception to week 20 of gestation; extended use thereafter was also studied. Antidepressants were categorized according to classes [selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and other antidepressants] and according to target transporters/receptors. Women not using any antidepressants during 15 months before delivery were included as reference. ResultsWe included 2,103 exposed and 95,376 reference women. Preeclampsia occurred in 70 exposed women (15 early-onset, 55 late-onset) and in 2,582 reference women (387 early-onset, 2,195 late-onset). TCA monotherapy (214 women) was associated with an increased risk of preeclampsia (n = 15, RR 2.46, 95% CI 1.51–4.02) and late-onset preeclampsia (n = 12, RR 2.41, 95% CI 1.39–4.17, early-onset could not be evaluated). No association was detected with SSRIs, SNRIs and MAOIs. We did observe an increased risk of early-onset preeclampsia following exposure to 5-HT2A antagonizing antidepressants (6/405 women, excluding TCA users, RR 3.56, 95% CI 1.60–7.94). ConclusionsOur results support an increased risk of preeclampsia and the late-onset subtype among TCA users. The association between 5-HT2A antagonists and the early-onset subtype needs to be interpreted with caution based on the relatively small number of exposed cases.
Highlights
Preeclampsia is one of the leading causes of maternal mortality and morbidity (Melamed et al, 2014)
Triptans were the only vasoconstrictors used in the exposed, whereas triptans and ergot alkaloids respectively accounted for 94% and 1.4% of vasoconstrictors used in the reference
We examined a wide range of transporters/receptors involved in the pathophysiology of preeclampsia
Summary
Preeclampsia is one of the leading causes of maternal mortality and morbidity (Melamed et al, 2014) It can be categorized into early-onset (before week 34 of gestation) and late-onset subtypes, involving the placenta as the central role. The former is associated with shallow in vasion of extravillous trophoblasts, reduced transformation of uterine spiral arteries, and/or fluctuations in placental perfusion. The latter may occur in mothers who are highly susceptible to a normal release of apoptotic trophoblast material or who encounter an increased release of factors from an enlarged placental surface (i.e. in multiple pregnancies, high altitude, anemia or diabetes mellitus).
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