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FDA: Appropriate SSRI Use OK in Pregnancy


 

Pregnant women taking selective serotonin reuptake inhibitors for depression may continue to do so, despite a 2006 warning that the drugs may predispose infants to persistent pulmonary hypertension, the Food and Drug Administration has announced.

That earlier warning was based on a single study indicating that infants exposed to the drug in utero after the 20th week of pregnancy were six times more likely to develop persistent pulmonary hypertension (PPHN) than nonexposed infants (N. Engl. J. Med. 2006;354:579-87).

“Since then, there have been conflicting findings from new studies evaluating this potential risk, making it unclear whether use of SSRIs during pregnancy can cause persistent pulmonary hypertension,” the FDA said in a press statement.

The agency will update the drugs' warning labels to reflect data from new studies, which have produced conflicting results about the risk SSRIs may pose to an unborn child. Those studies include a large retrospective database study in 2009 that found no association between SSRI use and PPHN (Pharmacoepidemiol. Drug Saf. 2009;18:246-52), and a 2011 case-control study of 11,923 births that showed PPHN was associated with cesarean delivery but not with SSRI use in the second half of pregnancy (Am. J. Perinatol. 2011;28:19-24).

FDA officials concluded that the evidence is not sufficient to withhold SSRI treatment from pregnant women or take them off the antidepressants. “At present, FDA … recommends that health care providers treat depression during pregnancy as clinically appropriate,” according to the agency's statement.

Dr. Gideon Koren, professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto, commented in an interview, “I support FDA's hesitation in confirming causation of SSRIs in causing PPHN. The available studies are split in their ability to show an association between SSRIs taken in late pregnancy.

“Critically, several studies have shown that depression itself is also associated with increased risk of PPHN. Hence it is quite possible that depression and not its treatment cause this rare risk ('confounding by indication').” Dr. Koren also heads the Research Leadership for Better Pharmacotherapy During Pregnancy and Lactation at the Hospital for Sick Children, Toronto, where he is director of the Motherisk Program.

Physicians and their patients should carefully weigh the risks and benefits of any antidepressant use in pregnancy, the FDA added, given that there are “substantial risks associated with undertreatment or no treatment of depression during pregnancy.” Risks of untreated maternal depression can include low birth weight, preterm delivery, lower Apgar scores, poor prenatal care, failure to recognize or report impending labor, and increased risks of fetal abuse, neonaticide or maternal suicide, the FDA warned.

Both the American Psychiatric Association and the American College of Obstetricians and Gynecologists recommend monitoring pregnant women for depression and treating them appropriately.

Physicians should continue to report any possible adverse effects to the FDA's MedWatch program, www.fda.gov/MedWatch/report.htm

Reporting forms can also be requested by calling 800-332-1088.

Dr. Koren said he had no relevant financial disclosures.

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Cautious Treatment Makes Sense

Even at the time of the first publication regarding the link between SSRIs and PPHN in 2006, the conclusion of the authors was that if the link is causal, the absolute risk for PPHN following late pregnancy exposure to SSRIs is very low. Thus, the recommendation that clinicians treat pregnant women appropriately for their symptoms was consistent with the initial findings, and continues to be so.

Since the initial publication, three others have appeared in full manuscript form and one in abstract form (now in press). The two published U.S. studies were either underpowered, or had limitations in classifying the outcomes, whereas the two Scandinavian studies confirmed the initial findings in large cohort or linked database studies. Importantly, the European studies that confirmed the association also came to the conclusion that SSRIs pose a small increased risk for a very rare outcome of pregnancy. Thus, the recommendation to treat only if needed, but not to avoid necessary treatment because of concern for PPHN continues to make sense.

CHRISTINA CHAMBERS, Ph.D., M.P.H., is associate professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said she currently receives grant funding for two studies unrelated to SSRIs from GlaxoSmithKline and GlaxoSmithKline Bio.

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