Are antidepressants safe during pregnancy?

(This article was first printed in the March 2006 issue of the Harvard Mental Health Letter. For more information or to order, please go to www.health.harvard.edu/mental.)

Since their introduction, antidepressants — especially selective serotonin reuptake inhibitors (SSRIs) — were considered fairly safe for pregnant women, even during the first three months, when the fetus is most vulnerable. But in late 2005, citing evidence from several sources, the FDA warned that infants exposed to the SSRI paroxetine (Paxil) during the first three months of pregnancy had an increased risk of birth defects.

The warning was based on unpublished reports from the drug’s manufacturer and data on thousands of births from a Canadian study in which mothers were interviewed and prescription records analyzed. The reviewers found that three types of defect were more common than average in the children of mothers who had used paroxetine during the first three months of pregnancy: heart defects, most often an opening in one of the walls separating chambers of the heart (ventricular septal defect); craniosynostosis, a malformation that occurs when skull bones fuse too soon; and omphalocele, protrusion of the intestines into the umbilical cord.

Other SSRIs were associated with omphalo­cele, although not as strongly as paroxetine. They were not linked to cardiac defects.

The risk of cardiac malformations in the children of women taking paroxetine increased 1½ to twofold, the risk of craniosynostosis and omphalocele 3–6 times. But heart defects are more worrisome because they are much more common — 1 in 100 births, or one-quarter to one-half of all major birth malformations. This compares to 1 in 2,200 for craniosynostosis and 1 in 4,000 for omphalocele.

There may also be a reason to avoid paroxetine at the other end of pregnancy. When a woman has been taking an antidepressant shortly before giving birth, the newborn may develop transient withdrawal symptoms. These symptoms are usually more intense with paroxetine, because it leaves the body faster than any of the other SSRIs.

Because of the FDA warning, many women are reconsidering their options. Some may be inclined to avoid all antidepressants during the first third of pregnancy. But the evidence has to be considered in a larger context: The findings are reason for caution, but not for alarm.

Maternal depression is a dreadful illness that causes much suffering. Depressed mothers find it hard to care for themselves. They miss doctors’ appointments and are more likely to drink alcohol or use illicit drugs. Some research suggests that children born of a depressed mother have lower birth weights. In extreme cases, depression can lead to the death of both mother and child. So antidepressant treatment may sometimes be necessary.

Fortunately, there are many good treatment options, with or without drugs. Women with milder depression may want to gradually reduce the dose of medication and rely on psychotherapy and family support from the time they try to get pregnant until the middle of a pregnancy. But that may not be a good choice for women with moderate to severe depression, especially since it’s not easy to predict when a child will be conceived. Fortunately, studies of other SSRIs have not shown a link to birth defects. Tricyclic antidepressants also appear to be relatively safe.

In some cases, planning is impossible. A woman who has been taking paroxetine might become pregnant unexpectedly and face a decision during the first trimester. In that situation, she might decide to bear the increased risk of birth defects rather than the risk of recurrent depression. If she does decide to stop taking paroxetine or switch to another drug, she should be sure to make any change gradually.

You can find more detailed information about treating depression (and other psychiatric illnesses) during pregnancy at www.womensmentalhealth.org.

(This article was first printed in the March 2006 issue of the Harvard Mental Health Letter. For more information or to order, please go to www.health.harvard.edu/mental.)

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