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Do No Harm: Weighing the Risks and Benefits of Antidepressants in Pregnancy

UH Clinical Update - May 2017

By Lulu Zhao, MD, Obstetrics & Gynecology, UH MacDonald Women's Hospital; Assistant Professor, Obstetrics and Gynecology, Case Western Reserve University School of Medicine Lu Lu Zhao, MD

An estimated 10 percent of reproductive-aged women currently suffer from major depression. Meanwhile, the rate of unintended pregnancy in America is nearly 50 percent. Combine the two, and you may find yourself confronted with a worried and pregnant woman who wants your advice on how to manage her depression and medications during the pregnancy. What knowledge and thought process will you use to guide her?

Personally, I start by asking if the woman has already made any changes to her medication regimen, and what effects she has noticed if she’s made a change. I then ask about the severity of the patient’s symptoms pre-treatment and how she did off of antidepressants in the past. Next, I ask the woman what her main concerns are – this step can be illuminating. Finally, I explore how much of a return of symptoms she is willing to tolerate, her ability and willingness to use alternative treatment such as cognitive behavioral therapy, and what events or benchmarks might indicate to her that resumption of medication is prudent.

It is important for women to know that the risk of symptom recurrence is very high for both discontinuing medications and reducing medications, at 70 percent and 50 percent, respectively. For someone who has been well-controlled on a particular medication, I typically do not switch the medication to a “safer” one: switching to an untested medication risks treatment failure and increases fetal exposure to psychiatric medications.

Overall, the data regarding fetal risk with antidepressant exposure is reassuring. This is especially true for sertraline, the most commonly used antidepressant in pregnancy. Some pertinent risks include:

  • Preterm Birth: Both mothers with untreated depression as well as mothers on antidepressants have an increased risk of preterm birth around 20 percent, compared to a population baseline of 12 percent. 
  • Cardiac Septal Defects: The increase in absolute risk is small, from five per 1,000 births to six per 1,000 births. This is true even for paroxetine, the only SSRI with a FDA Class D label. 
  • Persistent Pulmonary Hypertension of the Newborn (PPHN): This serious and sometimes fatal condition occurs at baseline in one to two newborns per 1,000 live births. With antidepressants, that absolute risk increases to 3.5 per 1,000 live births. 
  • Neonatal Adaptation Syndrome: This transient phenomenon occurs in up to 30 percent of babies. Infants who do not exhibit symptoms in the first 48 hours are unlikely to become symptomatic. 
  • Miscarriage, stillbirth, growth restriction, Cesarean section risk, and long term neurodevelopmental deficits have not been consistently shown to increase with SSRI use.

It is critically important for primary care providers and psychiatrists to be familiar and comfortable with the above counseling, as most women do not initiate prenatal care until after 11 weeks of gestation. Consistent messaging between providers enables women to make informed decisions with trust and comfort. These conversations – along with conversations about contraception – ideally occur throughout a woman’s care, so that she can make safe and appropriate decisions even in the face of unexpected events. Whether a woman ultimately decides to stay on her medications, or to commit to alternative treatment, it is our duty to provide her with the best possible information, so that she can make the best possible choice for herself and her baby.