Antidepressant use during pregnancy and development of preeclampsia: A focus on classes of action and specific transporters/receptors targeted by antidepressants

Objective: The 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. Methods: We 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. Results: We 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). Conclusions: Our 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.

Automated summary

The study found that users of tricyclic antidepressants (TCAs) have an increased risk of developing preeclampsia and the late-onset subtype, while 5-HT2A antagonizing antidepressants may increase the risk of early-onset preeclampsia.