Medication Exposure During Pregnancy: Antidepressants

Siobhan M. Dolan, MD, MPH

Disclosures

April 22, 2005

Although pregnancy is a joyful time for many families, approximately 10% to 20% of pregnant women experience major depressive symptoms during pregnancy.[1,2] This fact is not surprising given that the peak prevalence of depression for women occurs between ages 25 and 44 years,[3] almost identically overlapping their reproductive years. What is surprising, however, is how little data there are on the effect of antidepressant use during pregnancy. This article briefly reviews some of the issues associated with treatment of depression during pregnancy and lists some resources for physicians and patients.

Depression manifests as a depressed mood and a collection of symptoms that last for 2 weeks or longer. The symptoms include 5 or more of the following: sleep disturbances, lack of interest, feelings of guilt, loss of energy, difficulty concentrating, changes in appetite, restlessness or slowed movement, and suicidal thoughts or ideas.[4] Some of these symptoms, such as changes in appetite or sleep disturbances, may be considered "normal" for pregnancy. Some symptoms may be caused by medical conditions that commonly occur during pregnancy, such as anemia or hypothyroidism. These conditions can manifest as a lack of energy. But, if after a complete medical evaluation symptoms such as these persist and are interfering with daily life, further evaluation for depression is recommended, and various treatment options should be considered. Indeed, the risk factors that can accompany depression, such as inadequate weight gain, use of drugs or alcohol, or even suicide, most certainly have direct negative consequences for the fetus.

In many cases, behavioral therapy in the form of support groups, counseling, or psychotherapy is a good option for first-line treatment. Light therapy is an adjunctive treatment that has also been found to be helpful for some women. Consultation with a mental health professional can aid initiation of therapy/counseling and determine the need for medication. This assessment needs to balance the risks and benefits of the symptoms of major depression during pregnancy vs the risks and benefits of available medications.

If the decision is made to proceed to medication, there are options that have now been used for some time and thus are thought to be relatively safe. Because randomized controlled trials of medication do not include pregnant women, however, there are limited data assessing the effects of medication on pregnancy outcome. The data that are available generally derive from large cohort studies, toxicology centers, and pharmaceutical registries.

According to the United States Food and Drug Administration (FDA), the guidelines for assessing the category of risk for various medications are listed in Table 1 and Table 2 .[5,6]

Although the category B medication bupropion may seem a logical first choice, it's important to note that it is assigned category B only because there are no human studies; thus, its safety is untested.[7]

According to the Evidence-Based Medicine Working Group of the American Academy of Family Physicians (AAFP), the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) have been found in studies to be safe and effective in reducing the symptoms of depression.[8]

No studies have shown antidepressants to increase the risk of major malformations, although 1 study showed fluoxetine was associated with a greater risk for minor malformations.[9]

There is conflicting evidence regarding the association between antidepressants and perinatal complications such as preterm delivery. Several, although not all, studies showed an increased risk of premature birth among pregnant women taking fluoxetine.[3,9,10]

A withdrawal syndrome or neonatal toxicity, described as transient jerky movements (possibly seizures), respiratory distress, and feeding difficulties, has been reported in some babies born to mothers taking antidepressants.[3] This has prompted labeling changes for antidepressant medications that warn of the potential neonatal complications.

Studies evaluating long-term neurodevelopmental outcomes in children exposed to antidepressants in utero have not demonstrated a deficit in language, behavior, or IQ.[8]

Although both SSRIs and TCAs are considered safe and effective according to the AAFP review,[8] SSRIs tend to be associated with fewer side effects and are often considered first-line medications. That being said, the American College of Obstetricians and Gynecologists has not issued a practice guideline on antidepressant use during pregnancy. Therefore, critical to the management and treatment of depression during pregnancy is the individualized assessment and weighing of the risks and benefits of serious depression vs treatment options. Resources to assist patients and providers in undertaking these discussions are listed at the end of this article.

Many women are taking medication for depression before becoming pregnant and use the preconception visit as the time to discuss with their provider whether the need for medication is likely to be sustained during pregnancy. Abrupt discontinuation is not recommended, and many clinicians suggest that women at high risk for serious depression during pregnancy might best be served by continuing medication throughout pregnancy.[1]

Women with a history of depression and those who experience depression during pregnancy are at increased risk for postpartum depression. Although 50% of new mothers may experience mild symptoms such as "baby blues," between 10% and 20% of new mothers will experience postpartum depression[11] with serious ramifications that might include hurting oneself or the baby.

In addition to the options of seeking therapy and possibly medication, women who think they might be experiencing postpartum depression may benefit from joining support groups or calling telephone hotlines (see numbers below). As in pregnancy, a baby will be exposed to medication through breast milk, so clinicians and nursing mothers must consider similar risks and benefits in making treatment decisions around postpartum depression.

The Organization of Teratology Information Services (OTIS) provides fact sheets on the impact of the following medications on pregnancy. These medications are commonly used to treat depression.

Fluoxetine ( Prozac ):
https://otispregnancy.org/pdf/prozac.pdf

Sertraline ( Zoloft ):
https://otispregnancy.org/pdf/zoloft.pdf

Paroxetine ( Paxil ):
https://otispregnancy.org/pdf/paxil.pdf

Trazadone/Nefazadone ( Desyrel/Serzone ):
https://otispregnancy.org/pdf/Trazodone.pdf

Lithium:
https://otispregnancy.org/pdf/lithium.pdf

St. John's wort:
https://otispregnancy.org/pdf/stjohnswort.pdf

OTIS can be reached via phone at 866-626-6847 or on the Web at
https://www.OTISpregnancy.org .

Postpartum Support International -
https://www.postpartum.net/

Depression After Delivery -
https://www.depressionafterdelivery.com/Home.asp

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