The prevalence of major depressive disorders during pregnancy or the postpartum period is estimated to be between 10% and 15%.1,2
For the treatment of depression, SSRIs are the first-line pharmacotherapy. Antenatal and postpartum depression is a major concern for the health of both the mother and the newborn.
have shown an increased risk of VSDs in neonates exposed to paroxetine during the first trimester. This finding led the US Food and Drug Administration to advise women to avoid paroxetine during pregnancy if possible and to change pregnancy labeling from a category C to D. Paroxetine is the only SSRI whose pregnancy category labeling has changed. However, a recent meta-analysis23
that reviewed both previously published and unpublished data noted no association between paroxetine and cardiovascular defects.
In our study, 134 of the SSRI-treated mothers took paroxetine. None of the paroxetine-exposed newborns were diagnosed as having VSDs. In reviewing the 119 cases of paroxetine use during pregnancy for which all data were available, the average dose was 31.55 mg, with most exposures (76.47%) occurring at conception and continuing throughout pregnancy.
We found that SSRI use during the prenatal period is relatively low, occuring in 3.2% of our study population. We noted that doses of prescribed SSRIs are significantly lower if initiated during the second and third trimesters of pregnancy compared with those prescribed at the time of conception. This finding may demonstrate that some physicians may be hesitant to prescribe higher doses of SSRIs to pregnant women. It also raises the
question of whether the doses prescribed later in pregnancy are clinically useful.
In light of this and other research, important clinical questions include whom to treat and how to formulate an informed consent discussion. An informed consent discussion should include the risks of depression during pregnancy, nonpharmacological treatment options for depression, possible risks of SSRI exposure to the fetus, potential adverse effects to the mother, and benefits of SSRI use for treatment of depression. The patient's ultimate decision and the reason for her decision should also be discussed. Treatment is a personal decision between the patient and physician, with the balance weighing toward the patient's decision. Furthermore, physicians should have a similar discussion with all women of reproductive age when considering treatment with an SSRI because most of our patients were taking SSRIs at the time of conception. Accumulating data demonstrate the safety of SSRI use during pregnancy in terms of congenital defects; SSRIs should be considered for use during pregnancy when the benefit of treatment outweighs the estimated risk posed by medication exposure.
Our study has several strengths. We reviewed data throughout several years at a single medical center. In addition, the obstetrics database used is prospectively maintained. Although this is a tertiary medical facility, most of the obstetrics population is community based. We reviewed all pregnancies during this period, which certainly decreased our selection bias and allowed us to look at prescription practices. Because drug exposure information in our data was not based on a patient's memory, there is no possibility of recall bias.
Limitations of our study should not be overlooked. We did not review demographic or clinical information, including use of other prescription or nonprescription drugs, tobacco use, or alcohol use, that may affect fetal outcomes. Determining adherence to prescribed SSRI therapy during pregnancy is problematic. A patient who had SSRI use documented or prescribed during pregnancy but who did not ingest the SSRI would be misclassified as an exposure. Our data were taken from physician prescriptions rather than pharmacy records; the former may document an increased risk of nonadherence. Furthermore, we did not review the actual amount of time the fetus was exposed to an SSRI.
The ability to diagnose these disorders is also a concern; although PPHN would be diagnosed soon after birth, a small VSD may be undetected. Therefore, we may have underestimated the total number of heart defects. However, our overall rate of 0.8% is similar to previous CHD estimates of 0.4% to 1.0%,15-17
suggesting that we did not miss large numbers of outcomes.
Finally, we were attempting to study an association between a rare exposure (SSRI use during pregnancy) and a rare outcome (CHD in newborns), and, despite the large sample size, the study was underpowered to detect small associations. However, assuming an overall exposure rate to SSRIs of 3.2%, we had 80% power to detect an odds ratio of 2.4 with this sample size. An odds ratio of 2.4 would have represented an increased rate of CHD of 1.9% in SSRI-exposed newborns compared with a baseline rate of 0.8% in infants not exposed to SSRIs. We cannot rule out the possibility that the risk may have been lower, but our data suggest no increased risk in SSRI-exposed newborns.