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Prenatal antidepressants: time to concentrate on risk‐benefit ratio

In this month’s BJOG, authors from Australia and Denmark report perinatal and childhood outcomes associated with prenatal antidepressant exposure. Given the increasing use of antidepressants in pregnancy, this is a particularly timely and relevant topic. Studies evaluating the neurodevelopmental effects of antidepressant exposure during pregnancy have been conflicting, and few studies have reported long-term neurodevelopmental outcomes. Even fewer studies have adequately controlled for the effect of underlying mood disorders, independent of antidepressant use. Using the Danish National Birth Cohort, Grzeskowiak and colleagues report results of a population-based study of prenatal antidepressant exposure and childhood behavioral outcomes at age 7. After controlling for antenatal mood status and other confounders, there was no association between prenatal antidepressant exposure and increased risk of behavioral problems. Grzeskowiak et al. also report outcomes of a retrospective cohort study evaluating antidepressant use in late gestation with the risk of postpartum hemorrhage in Australia. Literature to date suggests prenatal antidepressants are associated with an increased risk for several adverse perinatal outcomes, including preterm birth, poor neonatal adaptation, and persistent pulmonary hypertension of the newborn. This paper contributes additional information regarding an association with postpartum hemorrhage, independent of maternal mental illness. Although the studies by Grzeskowiak et al. contribute important information to the literature, precise risk estimates that adequately account for confounders are difficult to derive. Studies evaluating the risk of antidepressants in pregnancy have generally lacked sufficient detail regarding the effects of specific medications and medication classes. There is insufficient data regarding the effects of timing of exposure and cumulative exposure. There is also a paucity of information regarding pharmacogenomics and whether a subset of the population may be particularly susceptible to adverse perinatal and long-term childhood outcomes related to antidepressant exposure. Because neurodevelopmental processes and outcomes may be distinct between sexes, studies powered for stratification of outcomes by sex are also needed. Separating the effects of antidepressant use from underlying maternal mental illness remains a substantial challenge worthy of additional focus. When it comes to prescribing antidepressant therapy during pregnancy, the challenge for clinicians remains the careful evaluation of risk–benefit ratio in individual patients. While determination of the risk-benefit ratio is critical, convincing a pregnant mother that continuation of depression medication may be lower risk than discontinuing medication can be very challenging. The knee jerk reaction of patients, and perhaps also physicians, tends to be discontinuation of maternal antidepressants during pregnancy due to real or perceived medication risks. There must be a thoughtful conversation about potential risks of therapy and about the very real risks of untreated maternal mental disease. With regard to pregnancy outcomes and subsequent neurodevelopmental outcomes of offspring, the accumulating body of research is largely reassuring regarding the safety of antidepressants during pregnancy. We need to keep risk–benefit ratio at the core of clinical decision-making. Additional prospective studies of the perinatal and neurodevelopmental consequences of antidepressant use in pregnancy, as well as the consequences of undertreating maternal mental illness, will inform risk–benefit discussions.