Pregnant Question

Depression Study Fuels Debate On Whether to Treat With Drugs

Volume 4 Issue 40

March 2005

A study last month in The Lancet, a major British medical journal, uncovered 93 cases of seizures in infants whose mothers had been taking selective serotonin reuptake inhibitor (SSRI) antidepressants, most commonly Paxil (paroxetine).

The article suggests that a baby whose mother is using SSRIs may suffer withdrawal symptoms including seizures when the child is born and abruptly stops getting the drug through the mother's bloodstream.

But the study -- based on a survey of reports of adverse drug reactions -- contains no definitive evidence of this effect. There has been no clinical trial comparing infants whose moms did and didn't take Paxil during pregnancy. (Paxil is available to pregnant women by prescription, though manufacturer GlaxoSmithKline says on its Web site that some complications, including seizures, have been reported in babies whose mothers had used the drug during pregnancy.)

However inconclusive, the Lancet report has provoked a new alarm about the effects of these antidepressant medications, whose safety in older children and whose impact on suicide has been widely questioned recently. It also has refocused attention on a crucial issue: Which is worse, the side effects of an imperfect but effective drug, or the serious condition it is intended to treat?

It is generally agreed that less medical intervention during pregnancy is better, since medications given to the mother may harm the fetus. But though often undiagnosed, depression in pregnancy is quite common, with an estimated 10 to 25 percent of pregnant women in the United States having clinical signs of depression.

More important, numerous studies have documented the adverse effects of maternal depression on fetal and infant well-being. Untreated depression during pregnancy has been associated in several studies with premature labor and low birth weight. A Danish study published in The Lancet in 2000 reported that maternal emotional distress led ultimately to congenital malformations. A study from Emory University in 2001 revealed that infants whose mothers had been depressed during pregnancy showed a higher than normal stress response at the age of 6 months. Depressed women are also at higher risk for using alcohol, drugs and tobacco, as well as for very poor diet and sleep habits, all of which have been shown to impair fetal development more than antidepressants do.

Continuing maternal depression is also a danger to the child during the postpartum and early childhood periods. Recent data indicate that maternal depression is a major predictor of poor bonding and negative parenting behaviors, including less interaction, more yelling and spanking.

"The poor-sleeping, poor-eating, high-stress condition of untreated depressed mothers-to-be [is] far more likely to lead to preterm birth or other complications in the newborn than antidepressant medication," said Andrei Rebarber, associate professor of maternal fetal medicine at New York University.

Rebarber said obstetricians need to carefully screen patients for common symptoms of depression: abnormal emotional instability, inadequate weight gain and possible substance abuse. How to Treat?

Once the decision has been made to treat depression during pregnancy, consideration should be given to psychotherapy, which is the first choice for mild to moderate symptoms. Interpersonal psychotherapy, where pregnant women work on developing new motherhood skills, has shown encouraging results in preliminary studies. Group psychotherapy, which helps treat social isolation, has also been recently shown to be effective.

But severe depression has been found to respond better to medication, with psychotherapy as a helpful adjunct. The decision to prescribe an antidepressant is based on the consideration that the risks of the treatment are outweighed by the risks of the depression. A psychiatrist should be involved, at least initially.

One psychiatrist with special training in this field is Shari Lusskin, director of reproductive psychiatry at New York University. Lusskin has studied the effects of depression on pregnancy and is convinced that early intervention can be beneficial for mother, child and family. "Exposure to maternal depression has long-term consequences on the fetus," said Lusskin, who recently authored a chapter titled "The Treatment of Psychiatric Disorders in Pregnancy" in Up to Date, an educational computer tool for clinicians. "We are beginning to understand the interplay of these factors at different points in fetal development."

Lusskin has identified several risk factors for depression during pregnancy, including a history of depression, a family history of mental illness, a lack of social support from spouse and friends, and anxiety about the fetus, especially if the pregnancy is unplanned. Screening for such factors is vital, Lusskin said.

"Pregnant women with severe depression can feel guilty about these symptoms and not reveal them," Lusskin said. "And doctors don't screen pregnant woman carefully enough for these symptoms." Some studies suggest that SSRI antidepressant use in pregnancy is relatively safe, though the wider body of research shows both risks and benefits.

A small seminal study published in the New England Journal of Medicine in 1996 showed that third trimester exposure to fluoxetine (Prozac) led to more premature deliveries and neonatal complications including poor tone, breathing difficulties and a weak cry.

But another study published in the American Journal of Obstetrics and Gynecology in 2003 reviewed records of 138 mothers on SSRI antidepressants during pregnancy and found no complications in the infants. Other studies have demonstrated temporary increases in jitteriness and delayed development in neonates whose mothers were taking SSRIs. But no studies have shown long-term effects at up to seven years.

Postpartum Factors

The Lancet study's suggestion that withdrawal seizures are linked to withdrawal of SSRIs is too speculative to be applied to clinical practice and too preliminary to greatly alter prescribing patterns. Ian Holzman, professor of pediatrics and chief of newborn medicine at Mount Sinai School of Medicine in New York, said he believes SSRIs are relatively safe, but he would like to see more studies over a longer period of time.

In the meantime, Holzman would prefer that the drugs not be given at the end of the third trimester in anticipation of a condition such as postpartum depression. "I wouldn't want to expose a baby for a non problem which may or may not occur," he said.

Lusskin disagreed, saying that postpartum depression, which occurs in the first five weeks after delivery at a rate three times greater than in a control group of non-pregnant women, often can be predicted by history, poor social support, marital strife and poor bonding with the infant. She said a drug like Paxil can be prescribed prophylactically for high-risk women.

Still, anticipatory prescribing before the end of pregnancy would lead some women to receive a drug they might not need -- an approach that might be difficult for an obstetrician to justify. The same factors are not involved in the decision on whether to breast-feed an infant when the mother is taking antidepressants. The direct effects on the infant -- of both the mother's depression and the drug to treat it -- are less severe.

First, the amount of the drug expressed in breast milk is less than one one-hundredth of what the fetus receives in the womb. Second, the mother may decide to continue the drug but stop breast-feeding, whereas she doesn't have a similar option while she's pregnant. The long-term health benefits of breast-feeding to the infant are well known. Holzman said that breastfeeding while on antidepressants is probably safe, and he doesn't recommend that mothers avoid it because of the medicine.

While the mother is still pregnant, the risk/benefit equations are more complex because two beings are involved. But by considering the mother first, and making sure she is in the best health possible, the baby tends to do better. This is why many obstetricians support the use of antidepressants during pregnancy. It is not a perfect situation, but for many women the risks of the disease far outweigh the risks of the drug.

"The number one person to treat is the mom," said Sreedhar Gaddipati, assistant professor of maternal fetal medicine and director of labor and delivery at New York-Presbyterian Hospital/Columbia University. "You have to ask yourself, 'Is this the same treatment you would give her if she weren't pregnant?' This is your starting point.

"Of course, once you've decided that she needs treatment, you have to choose the course of treatment that is the least toxic to the fetus."

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