Selective Serotonin Reuptake Inhibitor Use during Pregnancy and Major Malformations: The Importance of Serotonin for Embryonic Development and the Effect of Serotonin Inhibition on the Occurrence of Malformations

Abstract

Bioelectric signaling is transduced by neurotransmitter pathways in many cell types. One of the key mediators of bioelectric control mechanisms is serotonin, and its transporter SERT, which is targeted by a broad class of blocker drugs (selective serotonin reuptake inhibitors [SSRIs]). Studies showing an increased risk of multiple malformations associated with gestational use of SSRI have been accumulating but debate remains on whether SSRI as a class has the potential to generate these malformations. This review highlights the importance of serotonin for embryonic development; the effect of serotonin inhibition during early pregnancy on the occurrence of multiple diverse malformations that have been shown to occur in human pregnancies; that the risks outweigh the benefits of SSRI use during gestation in populations of mild to moderately depressed pregnant women, which encompass the majority of pregnant depressed women; and that the malformations seen in human pregnancies constitute a pattern of malformations consistent with the known mechanisms of action of SSRIs. We present at least three mechanisms by which SSRI can affect development. These studies highlight the relevance of basic bioelectric and neurotransmitter mechanism for biomedicine.