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Are Antidepressants Safe During Pregnancy?

By Dr. Eappen

The choice of whether to take a prescription medication during pregnancy is a difficult one, and one must weigh the potential risks and benefits to the unborn infant and mother.  When a mother has a potentially life threatening illness, the decision to take a prescription medication may be obvious. However, when a mother faces an illness not viewed as immediately life threatening, the decision to take a prescription medication becomes more complicated.  One area of controversy is the use and safety of antidepressants during pregnancy.

In our last blog post, we discussed potential risks of untreated prenatal depression, both to the mother and unborn infant.  Today’s post will focus on the use of antidepressants (specifically SSRI’s, also known as selective serotonin re-uptake inhibitors) for the treatment of depression and anxiety in pregnant women.  The SSRI’s are the most common medicines used to treat symptoms of depression and anxiety, particularly in those with major depressive disorder. For women with bipolar disorder (an illness which also has periods of depression), an entirely different group of medicines are used, which include antipsychotics and “mood stabilizer” medications.  The use of medications in managing bipolar disorder during pregnancy will be discussed in a separate blog post.

Why is prescribing antidepressants during pregnancy controversial? 

  1. Antidepressants are often considered “luxury” medicines, medicines that can and should be stopped in pregnancy.  This may stem from the belief that psychiatric conditions are not as serious as typical medical illnesses. 
  2. Antidepressants are often prescribed to those with mild symptoms of depression or anxiety.
  3. Untreated depression during pregnancy has risks to both mother and baby, some of which are discussed in this post. 
  4. A majority of women with major depressive disorder will relapse into having depressive symptoms if their antidepressant is stopped during pregnancy.

Why take an antidepressant during pregnancy? 

  • For women with a history of depression, discontinuing an antidepressant during pregnancy could result in a relapse of depressive symptoms in up to 70% of these women.  
  • Relapse of depressive symptoms then exposes the mother and developing infant to the effects of untreated depression.
  • Untreated depression during pregnancy is also one of the strongest risk factors in developing postpartum depression (PPD).  Left untreated, PPD can lead to impaired bonding between mother and child, and increased use of harsh discipline practices. More devastating consequences of untreated PPD including suicide (mother killing herself) and infanticide (mother killing her newborn).   

How reliable are the studies on the use of antidepressants in pregnancy?

In medicine, we depend on good evidence to provide good care.  However, the research base for the use of most medications during pregnancy is very poor.  Worries about testing medication during pregnancy, and causing potential harm to a developing fetus, has left us with slim evidence on the use of most prescription medicines in pregnant women.  As of July 2018, for 98% of the medications approved between 2000 and 2010, we do not know the risk of harm to the fetus. Further, it takes an average of 27 years after market approval for a drug to even be categorized in terms of risk.  As a result, unfounded concerns about fetal safety can lead to decisions to not prescribe or take a drug, which can cause greater risk of harm than the drug itself. It is not a clear risk of harm, nor a careful weighing of risks/benefits that leads to these medication discontinuations, but rather the absence of data that leads to these decisions.

Barriers that prevent good quality studies on this topic include ethical challenges, such as the inability to randomly assign treatments to pregnant women in clinical trials; as well as lack of an adequate comparison group in most studies, which makes it difficult to determine the role of an underlying depressive illness versus antidepressant use on a newborn’s outcome.   

I understand the data on the use of antidepressants in pregnancy is poor.  With that in mind, what are some potential risks of these medications?  

The FDA has published two “warnings” related to the use of SSRI’s in pregnancy.  One is a “black box” warning (the highest warning the FDA can give) regarding SSRI’s and their association with Persistent Pulmonary Hypertension (PPHN).  PPHN is a very rare condition that causes breathing difficulties in a newborn, and often leads to intubation. The other is a “public health advisory” (a milder warning compared to the black box warning) that includes information on the potential risk of relapse of depressive symptoms when women discontinue their antidepressants during pregnancy, as well as the risk of withdrawal symptoms in the newborn exposed to antidepressants in utero. 

Persistent Pulmonary Hypertension (PPHN)

PPHN affects 1-2 infants out of every 1000 in the general population, and carries a 10-20% mortality rate.  Factors that increase risk of PPHN include maternal cigarette use, maternal diabetes, and C-section. There have been three large studies that focus on this association, and their results are conflicting.  The first study was published in 2006, found the highest association between the use of antidepressants during pregnancy and PPHN, and provided the basis for the FDA alert. The baseline risk of an infant developing PPHN in the general population is 0.1-0.2%.  This study found that taking antidepressants during pregnancy increased that risk to 0.6-1.2%. The second study showed less risk, and the third and most recent study showed no association between PPHN and antidepressant use. As a result, even if we used the data from the study that showed the highest association of PPHN and SSRI use, and ignored the other studies that showed there was less risk, then we can anticipate that approximately 99% of women who use SSRI’s during pregnancy will give birth to a healthy infant without PPHN. 

Withdrawal Symptoms

In 2004, the FDA warned that third trimester exposure to antidepressants could be associated with “neonatal withdrawal syndrome”, as a result of withdrawal from the antidepressants.  Symptoms could include breathing problems, low blood sugar, vomiting, seizures, irritability and constant crying. However, the evidence behind this is poor, as there are inconsistent definitions in the available studies on what constitutes “neonatal withdrawal syndrome”, and no guidelines to evaluate the presence or absence of these symptoms.  As a result of this warning, many practitioners have weaned pregnant women off of antidepressants in the third trimester, despite not knowing whether doing so reduces the risk for withdrawal symptoms, and risking relapse of depressive symptoms. 

What is the safest antidepressant in pregnancy? 

There is no single safest antidepressant to take during pregnancy.  The choice should ultimately be made between you and your doctor.  

What are the antidepressants you can take while pregnant? 

With exception of Paxil, there does not appear to be any increased risk of major malformations when babies are exposed to most antidepressants.  First trimester exposure to Paxil has been associated with cardiac defects, and should ideally be avoided.  Prozac and Zoloft have the greatest amount of safety data since they have been available for several decades.  I have had many patients take Zoloft while pregnant, and have not witnessed any negative outcomes. 

I am considering continuing antidepressants during pregnancy.  What are some guidelines I should follow? 

Here are some rules of thumb that can be used when designing a treatment strategy:

  1. Minimize the number of exposures to the baby.  An example of an “exposure” is untreated psychiatric illness, and a single psychiatric medication.  So, if you are pregnant and taking two medications, avoid switching one of the medicines to a similar but different medicine, to avoid a new exposure.  Avoid discontinuing one of the two medicines if it would place you at risk for untreated psychiatric illness, which itself is another exposure. If you decide to breastfeed, avoid switching both medicines for something that you might think would be safer to use in pregnancy, as that would be two new exposures.  
  2. All medication changes should be done prior to pregnancy, if possible.  This minimizes the amount of exposures to the baby, and promotes mood stability for the mother
  3. Ideally, the patient should be stable from a psychiatric standpoint for at least 3 months prior to becoming pregnant.  This is not always practical to expect but can help minimize risk of mood instability during pregnancy.
  4. Use tried and true medications: older is usually better.  Just because a medicine is brand new, and has fewer side effects in non-pregnant individuals, does not mean that there are fewer risks in pregnant individuals.  If a medication has been available for several decades, then we will at least have some evidence on whether it has been associated with major problems when taken during pregnancy.
  5. If a baby was exposed to a medication during pregnancy, it may not make sense to discontinue the medication for breastfeeding.  The baby would have been exposed to a higher concentration of the medication in utero compared to the concentration found in breastmilk.  
  6. The decision to use an antidepressant during pregnancy or while breastfeeding needs to be made on a case by case basis, and should take into account severity of depressive symptoms (currently and in the past), the patient and partner’s wishes, the amount of medication needed to maintain stability in the past, history of suicidal/homicidal/psychotic symptoms, history of psychiatric hospitalizations, and countless other factors that are beyond the scope of this blog post.  
  7. Ideally, the OB/GYN, psychiatrist, primary care doctor, patient and patient’s partner should all be on the same page on whether a medication will be taken during pregnancy, and consultations with all of these individuals should be made well before attempting pregnancy to avoid risk of one of the doctors modifying the medication regimen and placing the mom at risk of destabilizing.

My take on using antidepressants during pregnancy

  • Antidepressant use during pregnancy is often necessary to prevent maternal psychiatric illness
  • Discontinuation of antidepressants during pregnancy increases risk of relapse, and exposes a baby to prenatal depression.  This exposure has been associated with poor outcomes for both baby and mother.
  • The overall safety of antidepressant use during pregnancy appears good, with only one exception (paroxetine).  
  • The association of SSRI antidepressants with PPHN has been seen in two studies, but the most recent third study did not support this.  The risk of this occurring in infants exposed to antidepressants remains very small, less than 1%.  
  • The decision on whether to take a medication for depression during pregnancy is not cut and dry.  The decision should take into account severity of current or previous episodes of depression, the amount of medicines historically needed to maintain psychiatric stability, and the wishes of the mother and her partner.  
  • Ideally, ensure that the OB/GYN, primary care doctor, patient/patient’s partner, and psychiatrist are all on the same page with regard to whether a particular medication regimen will be taken during pregnancy.

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About the Author

Seth Eappen, MD, is a board-certified adult, child and adolescent psychiatrist. Dr. Eappen completed medical school at the University of Illinois at Chicago and a residency at the University of Michigan, Ann Arbor. He completed his child psychiatry fellowship at MUSC in Charleston, SC, where he served as chief fellow. He is the founder of the Eappen Clinic, a private outpatient mental health practice with locations in Chicago and Oak Brook, IL.