A Mother's Dilemma: Using Antidepressants During Pregnancy

Reviewed by Jacqueline Brooks, MBBCH, MRCPsych
From the WebMD Archives

May 17, 2001 -- For years, conventional wisdom held that those magic hormones of pregnancy protected women from psychiatric illness such as depression. More recently, as recognition of depression during pregnancy has increased, doctors continue to shy away from using antidepressants for fear of harming the fetus.

But psychiatrists at last week's annual meeting of the American Psychiatric Association (APA) in New Orleans say there is an emerging body of medical evidence to suggest that it may be at least as important to consider the possible ill effects -- for both mother and baby -- of not treating depressed pregnant women.

Zachary Stowe, MD, reports that infants of mothers with a history of depression demonstrated an increased sensitivity to stress as measured by levels of cortisol, a naturally occurring hormone produced by the body in response to stress.

In the study, 19 6-month-old infants of mothers with a history of major depression were compared with 11 infants of mothers with no such history. Saliva was collected from the infants to measure the levels of cortisol their bodies produced.

The result: Infants of mothers with depression appeared to have higher levels of cortisol in their saliva -- indicating a greater response to stress -- than the infants of mothers who were not depressed.

"You could pick out the babies whose mothers were depressed during pregnancy," on the basis of their cortisol levels, Stowe says.

While much remains to be learned about the effects of different antidepressant drugs in pregnancy, there has been an "evolution" in thinking about the safest way to treat pregnant women who are depressed, says Lee Cohen, MD, from the department of psychiatry at Massachusetts General Hospital in Boston.

"When many of us trained to be physicians we were told that pregnancy was protective against psychiatric illness," Cohen says. "But now we have better data and we know that women are not protected against mood disorders in pregnancy."

An estimated 10% of women will experience major or minor depression during pregnancy, and more will suffer postpartum depression. Yet many women refuse treatment with drugs for fear of harming their babies.

By far, Prozac has been the object of the greatest amount of research for its effects in pregnancy. And the evidence seems to suggest that use of the drug in the first trimester is not related to adverse birth outcomes.

"The data support the absence of major malformations following first trimester exposure to Prozac," Cohen says.

Similarly, first trimester use of older antidepressants, known as tricyclics, also appears to be relatively safe. "There are good data supporting that when we use the tricyclics in the first trimester, you don't see higher rates of major malformations in children who were exposed to those medications," Cohen says.

But Cohen and others caution that much less information is known about selective serotonin reuptake inhibitors, or SSRIs, other than Prozac, like Paxil and Zoloft. "We cannot make assumptions about reproductive safety with incomplete data, even for medications that are in the same family," Cohen says.

Moreover, all of the research on antidepressant use in pregnancy pertains to short-term outcomes. Little or nothing is known about the long-term effects on offspring, researchers say.

Several studies presented at the APA meeting appear to support the relative short-term safety of using antidepressants during pregnancy.

In one study reviewing the obstetric and medical records of 70 infants whose mothers were exposed to antidepressants, there were no readily apparent negative outcomes associated with the use of antidepressants. But long-term neurological and behavioral effects of fetal exposure to these medications remain unknown.

That study was presented by Cohen and by Kimberly Pearson, MD, and Vicki Heller, MD, also of the department of psychiatry at Massachusetts General Hospital.

The study also concluded that it might be best to continue antidepressant medication through labor and delivery because after delivery, with the hormonal fluctuations, new expectations, and lifestyle changes placed on women, they are more vulnerable to postpartum depression.

A third study of 95 women compared obstetrical outcome for those who received antidepressant treatment with those who did not. There were no significant differences in obstetric outcomes between nonmedicated and medicated groups in each trimester, according to the study presented by Stowe and Noha Sadek, MD, of the department of psychiatry at Emory University School of Medicine in Atlanta.

When asked about antidepressant treatment closer to the time of delivery, Cohen says there have been reports of "jitteriness" in the babies associated with third trimester use of antidepressants.

But he says his own research suggests that the incidence of such problems is not great. And the possibility of a relapse to depression following delivery of the baby should make mothers cautious about discontinuing antidepressant treatment, he says.

"The incidence of clinically significant neonatal effects [related to late-term use of antidepressants] is extremely small, prompting us to never discontinue those medications for fear of relapse postpartum," he tells WebMD.

Stowe tells WebMD that much more research has been done on use of psychiatric drugs in pregnancy than any other kind of medication. Yet much of that research has been "generated out of fear that psychiatric medications do something bad," he says. "The evolution in thinking has been to understand what a bad idea that is."

Nevertheless, Stowe and Cohen emphasized that in the strictest sense no drug is perfectly safe, and that doctors can only speak to their pregnant depressed patients about relative safety of different medications. "I tell patients what we know and what we don't know," Cohen says. "What is safe for one woman isn't safe for another."