Women who take antidepressants during the final trimester of pregnancy through delivery increase the risk of "neonatal behavioral syndrome," a constellation of symptoms and behaviors largely related to drug withdrawal or side effects, University of Pittsburgh researchers conclude in a review of medical literature. Such findings reveal an additional challenge for clinical management of depression during pregnancy, Eydie Moses-Kolko, M.D., assistant professor of psychiatry at the University of Pittsburgh School of Medicine, and her colleagues write in the May 18 issue of the Journal of the American Medical Association.

"The FDA and drug manufacturers recently agreed to label revisions for antidepressants known as selective serotonin reuptake inhibitors. Now the label for these drugs includes information about potential adverse effects to newborns if the drug is taken late in pregnancy," said Dr. Moses-Kolko, who also is on staff with the Women's Behavioral HealthCARE program of the Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center. "Late exposure was associated with increased risk for a range of complications including jitteriness, stiffened muscle tone, irritability, respiratory distress and feeding problems."

While most cases of neonatal behavioral syndrome are mild and generally resolve in about two weeks, a number are severe enough to require neonatal intensive-care unit (NICU) hospitalization.

"Newborns exposed to antidepressants late in pregnancy had more than twice the risk of admission to a special-care nursery as those exposed only early in pregnancy," Dr. Moses-Kolko said, adding that late-exposed newborns also had twice the risk of respiratory complications - some critical. "Respiratory distress ranged from congestion and rapid breathing to extreme danger requiring oxygen therapy and even mechanical ventilation," she said. "A severe syndrome with dehydration, mechanical ventilation or seizures occurred in less than 1 percent of cases."

Even so, reports of prolonged hospitalization were rare, and no deaths related to neonatal behavioral syndrome have been noted. Medical interventions generally were limited to respiratory management, tube feeding and administration of sedatives, intravenous fluids and antibiotics.

The greatest number of antidepressant-related complication reports involved exposures to fluoxetine (Prozac) and paroxetine (Paxil). Complications related to sertraline (Zoloft), citalopram (Celexa) and venlafaxine (Effexor) were less frequent, but still significant, noted Katherine Wisner, M.D., M.S., professor of psychiatry and obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and senior author of the study.

"Uncontrolled maternal psychiatric illness during pregnancy carries its own dangers," added Dr. Wisner, who also is director of the Women's Behavioral HealthCARE program. "This can be associated with fussiness, irritability, inconsolability, diminished motor tone and lethargy."

Little is known about the consequences of fetal exposure to psychoactive drugs - indeed, many other drugs as well - while in utero. Because newborn behavior is shaped by countless variables, large controlled clinical studies are needed to establish the association between antidepressant-induced syndrome and complications due to other factors, the authors wrote.

Until large trials lead to some sort of treatment standard, clinicians must do the best they can to manage psychiatric illness during pregnancy even though data is limited, Drs. Wisner and Moses-Kolko said.

Strategies could include gradual tapering and cessation of drug treatment in the final weeks of pregnancy, but only after careful review and on a case-by-case basis.

"We still don't know whether a tapering strategy might be effective to limit neonatal behavioral syndrome, but an increased risk for maternal postpartum depression is well known," Dr. Moses-Kolko said. "Until we know more, treatment of the disabling disorder of depression must be a primary consideration."

Contact: Michele D. Baum
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Lisa Rossi
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