From Our 2007 Archives
Antidepressants and Pregnancy OK?
But Certain SSRIs May Boost Specific Birth Defect Risks, New Studies Show
Reviewed By Louise Chang, MD
But taking specific antidepressants may slightly increase the risk of certain birth abnormalities, the researchers say.
The two new studies, published in the June 28 issue of The New England Journal of Medicine, examined a type of popular antidepressants called SSRIs, or selective serotonin reuptake inhibitors. The drugs work by making more of the brain chemical serotonin available to the brain, thought to help in boosting mood.
While the results from the two studies are at odds on some points, they are in agreement on others. Paxil, for instance, was found to be strongly associated with specific defects. And the risks of certain birth defects, while increased, are still very small, the researchers say.
Concerns about birth defects associated with SSRI use began to surface three years ago, says Carol Louik, ScD, assistant professor of epidemiology at Boston University, Boston, and an author of one study. But research on SSRI use during pregnancy has produced mixed findings.
"There have been several studies in the past that have found an association between several SSRIs and certain birth defects, such as heart defects," says Jennita Reefhuis, PhD, an epidemiologist with the National Center on Birth Defects and Developmental Disabilities for the CDC, and a co-author of the other new study.
In 2005, the FDA alerted doctors and patients that the SSRI Paxil had been found to increase the risk of birth defects, especially heart defects, when it was taken during the first three months of pregnancy.
The new studies don't answer the question about the safety of SSRI use during pregnancy definitively, but they do add valuable information for women trying to decide. Both studies should reassure women, Louik and Reefhuis say.
CDC Study Details
Reefhuis' team evaluated data from 9,622 infants born with major birth defects and 4,092 infants born without birth defects, all delivered during the years 1997-2002. The data was obtained through the CDC-funded National Birth Defects Prevention Study, an ongoing effort that collects information from eight states.
The mothers participated in a telephone interview, answering questions about their exposure to antidepressants during pregnancy and one month before. In all, 3% of them, or 408, reported use of SSRIs during pregnancy or one month before they conceived.
The researchers evaluated four SSRIs, including Prozac, Zoloft, Paxil, and Celexa. Overall, no significant associations were found between the mother's use of the SSRIs and congenital heart defects, Reefhuis says. But they did find that Paxil use was linked to one type of heart defect, called right ventricular outflow tract obstruction defect, she says.
And they found an overall association between SSRIs and three other types of birth defects:
The increased risk ranged from 2.4 to 2.8 times higher, she says. But the numbers of infants affected, in each case, were small, she says. For instance, nine of the 214 born with anencephaly were exposed to SSRIs.
Early Antidepressant Use Study
Louik and her team evaluated birth defects and SSRI use in the first trimester of pregnancy in 9,849 infants with birth defects and 5,860 without, using data from the ongoing Slone Epidemiology Center's Birth Defects Study. "The point was to evaluate specific SSRIs and specific birth defects," she says. "What we found was although we didn't see an increased risk overall for SSRIs, there were some individual SSRIs that increase the risk for specific birth defects."
In contrast to the CDC study, her team did not find an association of a significantly increased overall risk for craniosynostosis, omphalocele, neural tube defects as a group, or overall heart defects. But they did find specific drugs are linked to specific defects.
"Paxil was associated with the defects that affect blood flow to the lung," she says. “Zoloft was associated with septal defects, the opening in the wall that separates the chambers of the heart. Those are ones we think are most credible."
Zoloft was also found to be linked to omphalocele, but she considers that association less credible. Only three of the 127 with this defect had been exposed to Zoloft.
Her study was partially supported by GlaxoSmithKline, the maker of Paxil.
Weighing the Benefits
Women should keep the risks of antidepressant use during pregnancy in perspective and weigh the potential benefits of SSRI use with their physician, Reefhuis says.
"Any pregnancy carries a risk of about 3% of having a birth defect regardless of exposures," she says.
The birth defects she found in her study to be linked to SSRI use are rare, she says. Craniosynostosis, for instance, occurs in one in 2,500 births, she says.
"Even if you quadruple the risk [of the three birth defects she found linked to SSRI use], there is still less than a 1% chance of having a child with that specific defect," Reefhuis says.
Clinical depression affects about 8% to 20% of women, Louik says, and during pregnancy, about 10% of women are affected. For some, antidepressants are the best treatment, she says.
Caveats: Antidepressants During Pregnancy
Women and their doctors should weigh the potential risks in the context of the risk of depression relapse during the pregnancy if the drugs are discontinued and the depression worsens, according to the American College of Obstetricians and Gynecologists.
In its committee opinion on SSRI use during pregnancy issued in December 2006, it recommends that treatment with SSRIs, if needed during pregnancy, be individualized. Paxil, it advises, should be avoided if possible by pregnant women and those planning to conceive.
Pregnant women shouldn't stop antidepressants abruptly, experts warn, because doing so could worsen the depression.
"The best recommendation one can make is for anyone pregnant and on these drugs to discuss it with their health care provider, usually their obstetrician," says Michael Katz, MD, vice president for research for the March of Dimes. He advises that a woman and her doctor decide together if it would be best to discontinue the drugs or to say on them and be closely monitored.
SOURCES: Jennita Reefhuis, PhD, epidemiologist, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta. Carol Louik, ScD, assistant professor of epidemiology, Boston University, Boston. Michael Katz, MD, senior vice-president for research, March of Dimes, White Plains, N.Y. The American College of Obstetricians and Gynecologists Committee Opinion: "Treatment with Selective Serotonin Reuptake Inhibitors During Pregnancy," December 2006. Louik, C. The New England Journal of Medicine, June 28, 2007; vol 356: pp 2675-2683. Greene, M. The New England Journal of Medicine, June 28, 2007; vol 356: pp 2732-2734. Alwan, S. The New England Journal of Medicine, June 28, 2007: vol 356: pp 2684-2692.
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