Depression treatment during pregnancy and breast-feeding
Recently published book discusses the risks and benefits of treatments for depression during pregnancy. The following is an excerpt from the book Depression and Bipolar Disorder: Your Guide to Recovery by William R. Marchand, MD.
This section will review the risks and benefits of treatments for depression during pregnancy. I will first discuss treatment with antidepressants.
Antidepressant treatment during pregnancy
Research indicates that women frequently take antidepressants during pregnancy,446 so it is very important for you to completely understand their pros and cons before making a decision. All antidepressants are believed to cross the placenta. This means that when a pregnant woman takes antidepressant medication, the unborn child is exposed to the medication as well. Many medications and substances that cross the placenta have some potential to harm the developing child. The first trimester of pregnancy is the period of fetal organ development. It is during these three months that the fetus is at greatest risk of the adverse effects of medications taken by the mother. Three general types of adverse effects can occur when a child is exposed to harmful substances before birth. The first is known as embryotoxicity. This means that exposure of the child to medication or harmful substances during pregnancy may cause some type of problem that occurs after birth but does not result in physical birth defects. Examples of this type of effect include the development of childhood behavioral problems and the child experiencing withdrawal symptoms after birth. A second possible adverse effect is known as teratogenicity. This means that there is a malformation of fetal organs or skeletal structures - in other words, a birth defect. Finally, the third adverse effect is the risk of miscarriage and problems at the time of birth, such as premature birth or caesarean section. Just to be clear, these are just general examples. I will talk about specific risks thought to be associated with antidepressants a little later in this section - but first a bit more background information.
In order to classify the risk of various medications to an unborn child, the U.S. Food and Drug Administration (FDA) uses five categories to indicate the potential of a drug that crosses the placenta to cause birth defects (Table 12.1). The rating given to a particular medication must be interpreted with care, however, because the level of evidence used to categorize individual medications varies from medication to medication as does the level of risk actually imposed by a particular drug. Thus, medications in the same category may have very different levels of risk and/or different levels of evidence supporting their categorization. The FDA has proposed major revisions in prescription drug labeling to give health care providers and consumers better information about the use of medications by women who are pregnant or breast-feeding. Thus, the categories listed in Table 12.1 may change in the future; consult the FDA website (http://www.fda.gov/) for the latest information. Finally, the FDA uses “black box” warnings on the labels of some medications when the FDA determines that a potential side effect is serious enough to warrant drawing the clinician’s attention to it right away.
Unfortunately, the potential risks and benefits of antidepressant treatment during pregnancy and breast-feeding are difficult to determine with certainty. First of all, for ethical reasons, there are no controlled trials of antidepressant use in pregnant women. What does this mean? To absolutely establish cause-and-effect relationships, studies would have to be conducted in which depressed women were randomly assigned to either take an antidepressant or not take an antidepressant and then become pregnant. Then the investigators would determine whether there was a higher risk of adverse effects among the children of those women who took the medication. In contrast, the information we have is from studies that do not clearly indicate cause and effect, often called “association studies.” An example of this is to compare a group of women who took antidepressants during pregnancy to a group who did not and see whether either group has a statistically significant difference in some particular outcome. If the children of the antidepressant group were found to have a higher incidence of a particular birth defect, then one could say that treatment with antidepressants is “associated” with that birth defect. The most these studies can tell us is that there might be a higher risk of certain outcomes if a medication is taken during pregnancy or breast-feeding. Many studies have other limitations as well, frequently involving what we call “confounding variables.” A confounding variable is a condition that may cause a study result to be incorrect. For example, a study might report that among the children of women taking a certain antidepressant while pregnant there were more cases of an adverse outcome than among the children of women who were not taking the medication. The adverse outcome might be a result of taking the medication; however, it might also be the result of a confounding variable. In this case, perhaps the effect of the depression itself on the child could be the actual cause.
Researchers try to control for these confounding variables, but it is often impossible to completely sort out the effects of one variable from another. Of course, the more studies that report a relationship between a specific medication and a certain adverse outcome, the more likely it is to be a “real” interaction, but in some cases it may be impossible to ever be absolutely certain. We just do not know enough about the risks of taking some medications during pregnancy or breast-feeding. In the following section, I will review some of the evidence that is currently available. As I have said elsewhere in this book, this information is presented to help you evaluate treatment options; it cannot replace a detailed discussion with your health care providers. Furthermore, new information will become available after this book is published. So, my aim is to help you think through possibilities but not to provide specific recommendations for your unique situation.
I will first discuss the issue of the effectiveness of antidepressant medication during pregnancy. As mentioned above, ethical considerations prohibit the studies that would absolutely answer this question. Nonetheless, at least one study suggests that antidepressant treatment during pregnancy can control depressive symptoms. Also, there is some evidence that stopping antidepressant treatment during pregnancy may result in relapse of depression. In contrast, a recent large study found evidence that taking antidepressants during pregnancy may not reduce the risk of developing a new episode of depression among women with a history of this illness. Given the limited and somewhat conflicting information available, it is difficult to know for sure whether antidepressants have the same effectiveness during pregnancy as when taken by individuals who are not currently pregnant.
There are also many unanswered questions about the safety of antidepressant use during pregnancy. Unfortunately, the available studies have many limitations and some have produced conflicting results.
Some studies suggest that antidepressant use during pregnancy might be relatively safe. One such study found that antidepressant use in the first trimester of pregnancy is not associated with an increased risk for major birth defects. Further, in a recent review the authors evaluated the safety of different classes of antidepressants and concluded that there was no convincing evidence of an increased risk for any adverse outcomes. In contrast to these reports, a fairly large body of literature suggests that at least some risk to the unborn child may be associated with taking antidepressants during pregnancy. For example, there have been reported associations between the use of these medications and increased rates of induced delivery and caesarean section, poor pregnancy outcome and neonatal withdrawal reactions, preterm births, and spontaneous abortion.
Among the classes of antidepressants, some experts have recommended the selective serotonin reuptake inhibitors (SSRIs) as the first choice if antidepressants are used for the treatment of depression during pregnancy. This is both because of the general favorable tolerability profile of this class of drugs and because a reasonable amount of reproductive safety data is available. Therefore, this chapter will focus on the use of SSRIs in pregnancy (see Chapter 8 for more information on SSRIs). In regard to FDA pregnancy category risks, all SSRIs are category C except paroxetine, which is category D (see Table 12.1 for a list of the categories).
A recent study found that prenatal exposure to SSRIs, especially during the first trimester, may modestly increase the risk of the development of autism spectrum disorders. Another study reported that infants exposed to SSRIs continuously during gestation were more likely to be born preterm than infants with partial or no exposure. However, the same study found no increased risk for minor physical anomalies or reduced maternal weight gain. One relatively large study466 of the risk of birth defects when SSRIs are used during the first trimester was published in 2007. That study of 9849 pregnancies found no increased risk of birth defects in women who took fluoxetine, citalopram, escitalopram, or fluvoxamine during the first trimester. However, all the studies discovered a small but statistically significant increased risk of certain birth defects in women taking sertraline or paroxetine during the first trimester. The authors pointed out that birth defects associated with SSRIs are rare and the absolute risks are small. Another large study of fluoxetine, sertraline, paroxetine, and citalopram467 found a small increase in the rate of certain birth defects in women taking SSRIs during the first trimester. Finally, there is some evidence suggesting a higher risk of newborns having a condition known as persistent pulmonary hypertension, which is a serious and life-threatening lung condition, when SSRIs were used during the final twenty weeks of gestation. As a result, the FDA issued a black box warning regarding the use of SSRIs and their possible association with an increased risk for pulmonary hypertension. The FDA also issued a Public Health Advisory entitled “Treatment Challenges of Depression in Pregnancy and the Possibility of Persistent Pulmonary Hypertension in Newborns,” which is available on its website (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm124348.htm). However, it is important to note that a more recent study did not find an association between SSRI use during pregnancy and pulmonary hypertension.
In regard to specific SSRIs, considerable data is available on the use of fluoxetine during pregnancy. Many studies have found no increase in the risk of birth defects. However, studies have reported an increase in spontaneous abortions, low birth weight, preterm delivery, and withdrawal-like symptoms. Finally, two studies have found no evidence of long-term developmental delays with fluoxetine. One other specific SSRI, paroxetine, warrants mention. There is evidence that the use of this medication during pregnancy may be associated with an increase in the risk of cardiovascular birth defects. For this reason the FDA recommended that the manufacturer of paroxetine change the drug to pregnancy category D in 2005. In contrast, a number of studies have found no adverse outcomes associated with paroxetine.
In summary, we do not have enough information to completely understand the risks of antidepressant use during pregnancy. SSRIs are most commonly used and have the most information available. The data we have suggests that taking antidepressants during pregnancy appears to be associated with some risk to the developing child. But, untreated depression can also be associated with risks for both mother and child. Later in this chapter I will discuss alternative approaches, such as psychotherapy. However, in some cases the benefits of antidepressant treatment during pregnancy may outweigh the possible risks, particularly for severe depression or when symptoms include thoughts of suicide or are causing significant disability. Please do not make a decision based only on reading this chapter. My goal is provide general information that may be helpful, but a book cannot consider all of the factors that may apply to your individual situation. Please discuss the options with your health care providers and your loved ones.
Antidepressant treatment while breast-feeding
Human milk is the ideal source of nutrients, immunological defenses, and growth-promoting factors for the newborn child; it provides the mother and child with both short- and long-term health benefits. As with pregnancy, information about the safety of antidepressant use when breast-feeding is limited. As in the preceding section, I will discuss only SSRIs in this chapter. In regard to SSRI effectiveness for postpartum depression, there is evidence of benefit. However, all antidepressants are excreted into breast milk and thus there is at least a potential risk of adverse effects in breast-fed infants of mothers who take these medications. Still, any potential risk must be weighed against the possible adverse consequences of not getting treatment. That said, there have been very few reports in the literature suggesting that infant exposure to SSRIs may be associated with adverse effects for the child.
In regard to specific medications, a number of studies have demonstrated that the concentration of sertraline in breast milk is generally low and is not detectable in the serum of breast-fed infants of mothers taking the drug. Furthermore, no adverse effects were observed in any of the infants who participated in these studies. When compared with sertraline, some other SSRIs result in higher concentrations in breast milk. While it makes sense to think that lower concentrations are better, in fact we do not know that undetectable levels of drugs have no short- or long- term effects, nor do we know that measurable drug levels in infant serum are associated with adverse events. A recent review concluded that either sertraline or paroxetine could be considered as the first choice among SSRIs for use during breast-feeding. However, other factors would need to be considered. For example, if one of these agents has been tried before and found to be ineffective for a given person, it would not make sense to try it again.
Psychotherapy treatment while pregnant or breast-feeding
Because of the lack of risk to the child, psychotherapy should always be considered as a treatment option for women who are pregnant and breast-feeding (see Chapter 9 for more about psychotherapies). As I have said elsewhere in this book, even if medications are used, I recommend that psychotherapy also be a part of the treatment plan in most cases. There have been a few studies of psychotherapy use during pregnancy. In particular, a controlled trial of interpersonal psychotherapy demonstrated this it was an effective antidepressant treatment during pregnancy. In regard to postpartum depression, several well-designed studies have shown various psychotherapy modalities to be effective, including cognitive therapy, psychodynamic psychotherapy, and interpersonal psychotherapy.
As you can see from the information provided earlier in this chapter, decisions about depression treatment during pregnancy and breast-feeding are complicated. This is due to the fact that potential risks and benefits for both mother and child must be carefully considered. Further, the consequences of both using and not using any potential treatment must be evaluated. Finally, we do not have enough information about the potential benefits and risks of antidepressant treatment during pregnancy and breast-feeding.
As I said earlier, the goal of this chapter is to provide information that may be helpful. All treatment decisions must be made as a result of discussions with your treatment team and loved ones.
My main recommendation is that, whenever possible, pregnancies should be planned well in advance. Plans should include depression treatment during both the pregnancy and when breast-feeding, if you plan to nurse your child. One recommendation that I like is to try to achieve a period of at least three months of stable remission before becoming pregnant. Though evidence is lacking, I think this approach could have three benefits. First, it may minimize the chances of a relapse during pregnancy. Second, it may prevent the need to change medications while you are pregnant or nursing. Finally, it may provide an opportunity for you to use the safest maintenance treatment possible when you become pregnant (see Chapter 14 for more about maintenance treatment). By that, I simply mean the treatment with the least risk for the child that is effective for you. For some, that may be psychotherapy alone. For others, it might mean using one of the antidepressants that we know the most about during pregnancy and breast-feeding. You may already know which maintenance treatment or treatment combination works best for you. If not, advance planning for pregnancy can provide the opportunity to determine that before getting pregnant. This could take a year or more because the longer you stay in remission as a result of a particular treatment, the more confident you can be that it works well for you. Also, you may need to try more than one approach to find what works best for you.
Even with advance planning, relapse is possible, so I recommend deciding before you get pregnant what steps you will take if relapse occurs. Having a plan in place can greatly decrease stress if your depression returns. For example, if you are receiving weekly psychotherapy, the first step might be to increase the frequency to twice a week. The second step, if necessary, might be to start an antidepressant. Of course, these are just examples. The point is that these decisions can be difficult and stressful, so try to make contingency plans in advance if you can.
Planning is good, but we all know life doesn’t always work out the way we plan. What if you are pregnant or breast-feeding now? The most important step is to talk to your treatment team and decide together what the safest approach is for your specific situation. There are many factors to consider when making treatment decisions (see Chapter 11); however, treatment with psychotherapy alone may be the safest option if you are experiencing mild depression. For more severe depression or mild depression that does not respond to psychotherapy, the risks versus benefits of medication treatment should be considered.
Excerpt from Depression and Bipolar Disorder: Your Guide to Recovery
William R. Marchand, MD
Copyright - 2012 by Bull Publishing Company
Bull Publishing Company