Obstetricians often see pregnant patients with psychiatric disorders, the most common being depression. Treatment includes both nonpharmacologic and pharmacologic options. This article focuses on use of selective serotonin reputake inhibitors (SSRIs), the drugs most often used to treat depression in pregnancy.1
Scope of the issue
A woman has a 10% to 25% risk of being diagnosed with major depressive disorder at some point in her life, with the greatest risk occurring during the childbearing years.2 It is estimated that 14% to 23% of pregnant women will experience a depressive episode while pregnant.3
The number of pregnant women in the United States using antidepressants during pregnancy ranges from 7% to 13%.4 As the number of pregnant women taking antidepressants has increased over the past 10 to 15 years, so has the body of literature investigating the safety and effects of these medications during pregnancy. Most of the studies are nonrandomized, increasing the risk of confounding and ascertainment bias. Results from many studies are conflicting, in part because past studies did not take into account the effect of depression or its severity.5 More recent studies, however, have incorporated propensity score matching, which attempts to equalize the variables among treated and untreated depressed women.3
The potential effects of SSRI exposure on the newborn are discussed here.
Poor neonatal adaptation
If SSRIs are abruptly stopped, neonates may demonstrate a constellation of symptoms similar to the withdrawal-type phenomenon seen in adults. Exposure in late pregnancy to SSRIs confers a 10% to 30% risk of poor neonatal adaptation (PNA) syndrome, although the true risk is not known.6 In most cases symptoms are mild and self-limiting. Some infants will require observation for a few days postnatally. It should also be noted that PNA may not be related to medication withdrawal at all. It could also reflect medication side effects (toxicity), nicotine withdrawal, or other factors common to women who take antidepressants.
To reduce the risk of PNA, or to possibly ameliorate neonatal symptoms, some researchers have suggested stopping SSRIs near term. This can have deleterious consequences for the mother and neonate, particularly in the vulnerable postpartum period. One recent study looked at the neonatal effects of continuing SSRIs until delivery compared to stopping them 14 days prior to delivery.7 Stopping SSRIs prior to term did not appear to improve neonatal outcomes. Importantly, these researchers used propensity score matching in an attempt to control for disease severity, although they did acknowledge limitations such as not controlling for maternal race and alcohol or tobacco use. Most studies in the past did not take into account the possible effects of depression or control for the severity of it. Thus establishing causal relationships between medication use and adverse outcomes proved difficult. Only recently has the focus shifted to also taking into account the effects of the disease itself.
Table 1 lists some of the features suggestive of PNA. This cluster of findings has also been called neonatal withdrawal or neonatal abstinence syndrome. It is unclear whether PNA is a withdrawal phenomenon or possibly reflects serotonin toxicity. It is important to alert a patient's pediatrician about maternal SSRI use and to counsel the patient about the possibility of PNA. As noted in a recent review examining risks versus benefits, if pharmacotherapy is indicated the potential benefits outweigh the possible risks of PNA.8