Prenatal antidepressant exposure: clinical and preclinical findings

Pharmacological treatment of any maternal illness during pregnancy warrants consideration of the consequences of the illness and/or medication for both the mother and unborn child. In the case of major depressive disorder, which affects up to 10-20% of pregnant women, the deleterious effects of untreated depression on the offspring can be profound and long lasting. Progress has been made in our understanding of the mechanism(s) of action of antidepressants, fetal exposure to these medications, and serotonin's role in development. New technologies and careful study designs have enabled the accurate sampling of maternal serum, breast milk, umbilical cord serum, and infant serum psychotropic medication concentrations to characterize the magnitude of placental transfer and exposure through human breast milk. Despite this progress, the extant clinical literature is largely composed of case series, population-based patient registry data that are reliant on nonobjective means and retrospective recall to determine both medication and maternal depression exposure, and limited inclusion of suitable control groups for maternal depression. Conclusions drawn from such studies often fail to incorporate embryology/neurotransmitter ontogeny, appropriate gestational windows, or a critical discussion of statistically versus clinically significant. Similarly, preclinical studies have predominantly relied on dosing models, leading to exposures that may not be clinically relevant. The elucidation of a defined teratological effect or mechanism, if any, has yet to be conclusively demonstrated. The extant literature indicates that, in many cases, the benefits of antidepressant use during pregnancy for a depressed pregnant woman may outweigh potential risks.