Neurodevelopment of Children Exposed in Utero to Antidepressant Drugs


Synopsis: The present study did not document any untoward effects of in utero exposure to either tricyclic or fluoxetine antidepressants upon global intelligence, language development, or behavioral development.

Source: Nulman I, et al. N Engl J Med 1997;336:258-262.

Both tricyclic antidepressants and fluoxetine cross the placental barrier. As discussed in a previous issue of OB/GYN Clinical Alert (1996;13:61-62), Chambers et al (N Engl J Med 1996;335:1010-1015) reported on the outcome of 228 mothers who took fluoxetine during pregnancy. They found that women who took fluoxetine in the third trimester were at increased risk for perinatal complications. On the basis on their data, they recommended that women discontinue antidepressant therapy in the third trimester. However, Nulman et al note that discontinuation of antidepressants during pregnancy is associated with high relapse rates and that when maternal depression is not adequately controlled, there is ample evidence of adverse developmental outcomes and higher perinatal risks. These sequelae could well be due to the neuroendocrinological aberrations induced by depression. On the other hand, fetal brain development continues beyond the first trimester, and exposure to antidepressants is cumulative. Given that an estimated 10-20% of women of childbearing potential are depressed, the need to delineate the optimal clinical strategy for the treatment of depressed, pregnant women is high. The investigators found no evidence that in utero exposure to tricyclic antidepressants or fluoxetine compromised global intelligence, language development, or behavioral development in the 135 children so exposed who were evaluated at 24 and 30 months of age.


This is an important study, but it does have its limitations. First, the sample size is small. Second, the length of follow-up is short. While the data are indeed reassuring, what one really wants to know is how these children will fare when they go to school. I hope that there is sufficient funding available in Canada to permit these investigators to follow this cohort and to add to it. Everyone knows that drug exposure during pregnancy is to be avoided. What few appreciate is that depression is a biochemical state that in and of itself may compromise fetal well-being. It is entirely possible, therefore, that antidepressant exposure is the lesser of two evils in this regard. Women who are depressed often seek a second opinion and reassurance from their obstetrician. Thus, it is important for us to have more than a passing familiarity with this therapeutic dilemma. On the basis of these recent studies, I believe it is most appropriate to tell patients that the benefits of antidepressant therapy during pregnancy outweigh the risks of discontinuation, even during the third trimester.