TCPR: Dr. Hendrick, earlier this decade, most experts felt that SSRIs were relatively safe in pregnancy, but lately the pendulum seems to be swinging in the other direction. What do you consider to be the major risks of SSRIs in pregnancy?

Dr. Hendrick: The adverse outcomes can be broken into four general categories: first, a greater risk of perinatal complications in the newborn right at birth; second, birth defects, especially cardiovascular anomalies like atrial septal defects; third, persistent pulmonary hypertension of the newborn; and finally, miscarriage. But it is important to realize that while SSRIs have some adverse effects, untreated depression during pregnancy has been found to have higher rates of some of these outcomes as well.

TCPR: Can you describe some of this research?

Dr. Hendrick: One good study, with nearly 120,000 participants (Oberlander et al., Arch Gen Psychiatry 2006;63:898-906), compared three groups of pregnant women born in British Columbia: depressed women who took SSRIs, depressed women who did not take SSRIs, and a control group of non-depressed women who were not on medication. What they found was that depressed women who were not on medication had worse outcomes than non-depressed women (also on no medication). Specifically, their babies were more likely to be preterm, have low birth weight, and have respiratory distress. Nevertheless, the greatest risk of poor outcome was in the SSRI-exposed moms. So it looks like depression alone can cause poor outcomes, and that SSRIs seem to cause independent risk.

TCPR: And how might untreated depression lead to these poor outcomes?

Dr. Hendrick: Untreated depression has been linked to missed prenatal doctor’s visits, substance abuse, and smoking. In general, when studies have controlled for maternal health habits, depression alone is not linked to poor outcome; it is the poor health habits of depressed women that seems to be crucial.

TCPR: That’s somewhat reassuring. In my own practice I commonly see pregnant women who are depressed and yet do not want to take medication. It sounds like what you are saying is that as long as they appear to be taking care of themselves and their health, I needn’t be concerned that the depression per se will harm the fetus.

Dr. Hendrick: Yes, that’s right. As long as they are gaining weight adequately and following up with all their prenatal visits, just the fact that they are depressed shouldn’t lead to a worse outcome. However, if they have depression with anxiety as well, which is very common in pregnant women, then there are some theoretical concerns, because higher levels of stress hormones early in the third trimester has been linked with preterm labor. So, if a woman is highly anxious, the anxiety itself, even with good health habits, could lead to a greater risk of an adverse outcome.

TCPR: Let’s talk about Paxil (paroxetine). Most authorities consider this medication to be relatively contraindicated in pregnancy because of the risk of cardiac abnormalities. But the studies have often clashed with one another. What’s your take on the issue?

Dr. Hendrick: The studies can be confusing. One of the general rules of thumb I use in interpreting pregnancy studies is to look at how consistent the data are. If only a single study finds a certain outcome, then it is not going to be as compelling as if several studies have found the same poor outcome. Likewise, the “poor outcome” should be the same birth defect. In this case, there have been a variety of cardiovascular defects linked with SSRIs, and that argues a bit against the link between a prenatal exposure and the cardiovascular defect.

TCPR: Have the Paxil studies consistently shown any particular cardiovascular defect?

Dr. Hendrick: Yes, a number of studies have linked paroxetine with atrial septal defects and ventricular septal defects, and this concerns me enough that I recommend that paroxetine not be used in pregnancy. In addition, paroxetine is the only SSRI that has been bumped down to category “D” by the FDA (there is evidence of risk in humans), making it a medical-legal risk. But it’s important to note that not all experts agree with the negative perspective on Paxil, and seemingly contradictory results are published frequently. That said, I don’t worry too much about the cardiovascular defects of SSRIs, because even if there is a genuine association, the risk appears to be very tiny. My biggest concern is with the respiratory distress that has been linked with SSRI exposure.