Abstract
Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb serotonin homeostasis in the fetoplacental unit by inhibiting serotonin transporter (SERT) and organic cation transporter 3 (OCT3) in the maternal- and fetal-facing placental membranes, respectively. Paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and venlafaxine were tested in situ (rat term placenta perfusion) and ex vivo (uptake studies in membrane vesicles isolated from healthy human term placenta). All tested antidepressants significantly inhibited SERT- and OCT3-mediated serotonin uptake in a dose-dependent manner. Calculated half-maximal inhibitory concentrations (IC50) were in the range of therapeutic plasma concentrations. Using in vitro and in situ models, we further showed that the placental efflux transporters did not compromise mother-to-fetus transport of antidepressants. Collectively, we suggest that antidepressants have the potential to affect serotonin levels in the placenta or fetus when administered at therapeutic doses. Interestingly, the effect of antidepressants on serotonin homeostasis in rat placenta was sex dependent. As accurate fetal programming requires optimal serotonin levels in the fetoplacental unit throughout gestation, inhibition of SERT-/OCT3-mediated serotonin uptake may help explain the poor outcomes of antidepressant use in pregnancy.
Highlights
Depression is one of the most frequent complications during pregnancy
MVM and BM vesicles were used to evaluate the effects of antidepressants on serotonin transporter (SERT)- and organic cation transporter 3 (OCT3)-mediated uptake of 5-HT, respectively. (b) To confirm our ex vivo findings on organ level, in situ perfused rat term placenta was employed to explore the effect of antidepressants on OCT3-mediated
Membrane vesicles isolated from human term placenta were used to study the tested antidepressants’ inhibitory effects on 5-HT transport across the MVM and BM
Summary
Depression is one of the most frequent complications during pregnancy. Estimates of its prevalence vary significantly, but recent data indicate that up to 20% of pregnant women experience depression and/or anxiety [1]. Currently up to 13% of pregnant women are prescribed one or more antidepressants, most commonly selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs) [3,4]. These drugs inhibit reuptake of serotonin (5-hydroxytryptamine, 5-HT) in neuronal cells by blocking its specific transporters in the presynaptic membrane, increasing extra-neuronal 5-HT concentrations in the brain.
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