Selective serotonin reuptake inhibitors in human pregnancy: on the way to resolving the controversy

There has been an increase in the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. However, in the last 10 years, in spite of a vast literature regarding use in pregnancy there seems to be some confusion as to the possible risk of these drugs, especially related to cardiovascular anomalies. In addition, there are data on developmental follow-up studies that raise the question of possible slight developmental and neurobehavioral problems. The purpose of the present review is therefore to critically summarize the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. Although most studies have not shown an increase in the overall risk of major malformations, several have suggested that the use of SSRIs may be associated with a small increased risk for cardiovascular malformations. However, new compelling evidence shows that this apparent increased risk occurs also in women with untreated depression, highlighting the probable ascertainment bias involved in many of these studies. Persistent pulmonary hypertension of the newborn (PPHN) has also been described with an absolute risk of <1%; however, here too, higher rates were described among offspring of women with untreated depression. Poor neonatal adaptation has been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Of the few postnatal developmental follow-up studies, there are no significant developmental problems. The literature on SSRIs in pregnancy is somewhat confusing but when analysing all prospective cohort data there seems to be no demonstrable increase in the rate of major anomalies or developmental disorders. When evaluating the risk/benefit ratio of SSRI treatment in pregnancy, the risk associated with treatment discontinuation - e.g. higher frequency of relapse, increased risk of preterm delivery and postpartum depression - appear to outweigh the potential, unproven risks of treatment. Moreover, maternal depression may negatively affect the child's development, emphasizing the importance of prevention by appropriate treatment during pregnancy with the least minimal effective dose.