The Use of Selective Serotonin Reuptake Inhibitors for Major Depression during Pregnancy
By David Schatz, MD
Treatment of medical illness during pregnancy is often complicated. Though the common medications used to treat illness can do wonderful things, a certain number can have negative effects on the unborn child. Thus, a mother and her doctor are left with the difficult decision of deciding if a treatment during pregnancy is worth the possible risk to the baby. Nowhere are these facts truer than in the treatment of Major Depressive Disorder (MDD) during pregnancy. MDD is common among women of childbearing age. Studies have found rates of MDD during pregnancy which range from 9% and 21%[i]. After delivery of the infant, hormones such as estrogen and progesterone drop dramatically. This rapid drop in hormones is similar to what occurs when a woman goes through menstruation, but it is much more dramatic. The change in hormones is one of the factors which contribute to the high incidence of postpartum depression, which is depression after giving birth. A study found that 6.5% to 13% of women had MDD in the months after they gave birth[ii]. It is important to note that MDD includes significant guilt, lack of ability to enjoy things, poor appetite and sleep, and possibly suicidal ideation. These symptoms must be differentiated from post partum ‘blues’, which affects 80-90% of women after birth. Postpartum blues are transient depressive symptoms which usually resolve approximately 2 weeks after giving birth. Major Depressive symptoms always continue for longer than two weeks. When a woman has MDD either before or after giving birth, she is faced with the decision of whether to treat her symptoms. The most common medication treatments for MDD are antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs). These medications include Prozac, Paxil, Zoloft, Celexa, Lexapro, and Luvox. The purpose of this article is to discuss the risks and benefits of using these SSRIs to treat MDD during pregnancy. It will also discuss other non-pharmacological treatments options for MDD such as psychotherapies. This article is meant as an aid to help you work with your doctor to make these important medical decisions during your pregnancy. It is important that you speak with your doctors regarding this decision, even if your plan is to not use medications.
As I alluded to above, the decision of whether to use SSRIs during pregnancy should take into account a couple of factors. First, you should think about the risks of the medications (which will be discussed below) and the benefits of the medications (treating your depression). You also, however, must think about the risks of having untreated depression. When it comes to depression, many mothers assume that if they do not treat the illness, they will just “feel bad”. They don’t think that this depression itself would have any negative consequences for their baby. Unfortunately, the risks of untreated depression can actually cause harm during pregnancy. Women who are depressed and who do not undergo treatment have children with lower birth weight, children who are more likely to be preterm, and children who are more likely to have respiratory distress. Further, women with untreated depression were more likely to have cesarean sections and to be admitted to the neonatal intensive care unit[iii]. Finally, it has been shown that depression after the child is born adversely affects mother-child bonding during the first year of life[iv]. This fact is significant given our knowledge that the development of the baby’s brain occurs rapidly during the first year of life. The mother’s attunement to the needs of the baby is crucial during this time to ensure an optimal environment for the baby’s development. Studies, for example, have shown that children of mothers with post-partum depression are more likely to have increased depressive and anxiety symptoms later in life, along with difficulties with attachment to the mother. It concerns me that, during discussions of the risks and benefits of psychiatric treatment for depression during pregnancy, people often neglect the risks of untreated depression during and after pregnancy, and instead choose to focus on the risks of psychiatric treatments such as medications.
This is not to say, however, that medications are without risks. Before I begin to discuss the risks of psychiatric medications during pregnancy, it is important to note that medications are most certainly NOT the only treatment for depression during pregnancy. Therapies such as cognitive behavioral therapy and interpersonal psychotherapy have been shown to be every bit as effective as medications[v] . Psychotherapy is a way to both treat your depression and to not expose the developing child to medications. Beyond psychotherapy, you can engage in activities which will promote your mental health, such as yoga and exercise. Making sure your intimate partner also prioritizes your mental health during pregnancy is another way to treat mild depressive symptoms and help to avoid the use of medications. Many times, however, women do not have access to the above mentioned psychotherapy and treatment options. Moreover, for severe depression medications should be the first line treatment, because psychotherapy generally takes longer to have its effect.
Thus far, we have discussed the risks of untreated depression during and after pregnancy, and I have suggested other treatments for depression besides medication. Now we will discuss one of the most difficult parts of the decision to use medications or not. This difficult topic is the possible effects of SSRIs on your developing child. Psychiatric medications used during pregnancy do carry some risks. These risks can roughly be divided into 4 categories: first, a greater risk of adverse effects in the newborn right at birth; second, birth defects, especially anomalies of the heart; third, persistent pulmonary hypertension of the newborn (which will be explained below); and finally, loss of the developing child (miscarriage).
Before we being the discussion of these adverse effects, it is important to realize that the data regarding the safety of antidepressants during pregnancy can be VERY confusing (you thought pregnancy was going to be easy? Well I thought getting through medical school was going to be easy. Guess we were both wrong…). The reason for this confusion is that we as doctors cannot ethically conduct the best studies necessary to find out whether medications are safe or not. Such studies would require us to randomly decide which women take antidepressants during pregnancy and which women do not. Moreover, to truly figure out whether the negative effects of antidepressants are caused by the medications themselves, as opposed to the depression they are being used to treat, we would also need to give women WITHOUT depression antidepressants. Clearly, forcing women to take antidepressants when they don’t want to do so is not ethical. Thus, doctors have to draw conclusions about medications during pregnancy from less than ideal information. Another dilemma is that many of the studies which have been done come up with different and conflicting results. Thus, it is hard to know which study to trust.
So at this point, you might be saying “great, that means we can’t draw any conclusions about anything!” I do hope that I have not tarnished the image of medical science by my above discussion. The information we do have is still useful in making decisions regarding medications during pregnancy. The above uncertainty which I discussed simply means that each decision to use medications vs. to not use medications has to be an individual decision between you, your family, and your doctor. So, with all that being said, here is a summary of what the data on SSRIs shows currently. We have the most information regarding Prozac, because this medication has been around the longest. One study examining Prozac indicated that there might be an increased incidence of outcomes such as such as miscarriage, low birth weight infants, and preterm delivery. Again, these effects need to be weighed against the risks of untreated depression, which were also miscarriage, low birth weight infants, and preterm delivery. There also appears to be an increased risk of side effects in the newborn shortly after birth, such as high pitched crying and tremor. These effects are thought to be symptoms of withdrawal from the SSRI in the newborn infant. Luckily, this syndrome does not appear to adversely affect the infant overall. There appear to be, for example, no negative long term consequences on the development of the brain of the child after being exposed to Prozac[vi].
Two studies looking at Prozac and the other SSRIs have found an increased incidence of a rare birth defect, omphalocele[vii], [viii]. Omphalocele is a congenital (found at birth) malformation in which variable amounts of abdominal contents protrude into the base of the umbilical cord. Although this effect clearly sounds very scary, it is important to remember that the risk of omphalocele occurring is still extremely low and this increased risk needs to be confirmed with other studies. One of the above studies, Alwan et al (2007), also found an increased risk of anencephaly and craniosyntosis. Again, the risks were still very small, and these conclusions need to be confirmed with future studies.
Another recent finding that is the concern that SSRIs can significantly increase the risk of a disease called persistent pulmonary hypertension of the newborn (PPHN)[ix]. This disease leads to initial difficulty breathing in the newborn child. This is a very important finding which should obviously be taken into account when considering the use of SSRIs during pregnancy. It should again be kept in mind, however, that the absolute risk of PPHN is still fairly small. Moreover, the cases of PPHN caused by SSRIs were relatively mild, and there were no long term negative consequences to the child.
Paxil is an SSRI which bears special mentioning because recent studies have found that Paxil may slightly increase the risk of heart defects[x]. This caused the Food and Drug Administration to change the category of risk for Paxil from C (which is where all the other SSRIs are) to D. Without going into the details of the FDA’s categories of risk, suffice it to say that the FDA considers Paxil to be less safe during pregnancy than other SSRIs. Although the studies which showed this increased risk of heart defects has been debated, at this point it makes the most sense to use one of the other SSRIs such as Prozac, Zoloft, Celexa, or Lexapro.
Phew. That was a lot of information. Let me try to summarize the overall content of this article. First, depression during pregnancy is common. Untreated depression itself can have negative effects on pregnancy outcomes. Depression after pregnancy is even more common, and can adversely affect maternal-infant bonding and possibly the emotional development of the child. Thus, the decision regarding how to treat depression during pregnancy is an important one. If the depression is more mild, changes in a person’s life such as increased social support or general wellbeing measures such as Yoga or exercise may be tried. If the depression is mild to moderate and the woman wants to avoid medications, psychotherapies such as cognitive behavioral therapy and interpersonal therapy may be utilized. If, however, the depression is more severe, there should be a strong consideration regarding the use of medications. Studies do show that there is an increased incidence of negative birth outcomes, but as stated above, depression also can cause these same outcomes. More concerning are studies which indicate that there is an increased risk of birth defects such as omphalocele, anencephaly, craniosyntosis, and persistent pulmonary hypertension of the newborn. These effects are certainly concerning, but it is important to remember that, although SSRIs increase the risk of these defects, the absolute risk is still very low. It is also important to remember that the studies which determine these risks are far from ideal, because ideal studies cannot be ethically done. Thus, even armed with all the information available on SSRIs during pregnancy, the decision still needs to be an individual one which you make in consultation with your family and your doctor. I hope that this article has not been an overly confusing one which has made your decision more difficult. I wish you the best in this important time in your life.