Study Finds Some Risk in Prozac Use in Pregnancy
In a new study of women who took Prozac while pregnant, UC San Diego researchers uncovered no evidence that the drug causes major birth defects or miscarriages, but did link it to a higher risk of premature birth and babies with fleeting medical problems such as jitteriness and breathing trouble.
The study, published today in the New England Journal of Medicine, is the first to suggest that the widely used drug has even a slight adverse effect on human fetal development and newborn health. The findings are already provoking heated debate among researchers and confusion among physicians and patients.
Citing the new research, the March of Dimes, a birth defects foundation, said pregnant women “should try to avoid taking . . . Prozac if possible until the drug’s effects in pregnancy have been studied further.”
But other medical researchers and the drug’s maker, Eli Lilly and Co., sharply criticized the study’s methods and questioned some of its conclusions.
About 14 million Americans have taken Prozac, or fluoxetine, the nation’s No. 1 prescription drug for depression. Although researchers could not say how many pregnant women take the drug, it is prescribed to about 2.3 million women between the ages of 20 and 39. Potentially, hundreds of thousands face the dilemma of staying on Prozac during pregnancy, researchers say.
“We would hope that women who do not really have to be on the drug would choose to go off it” if they are pregnant, said Dr. Kenneth Lyons Jones, a UC San Diego pediatrician who led the study. “Women who continue taking that drug up to the time of delivery need to be aware of these problems,” which, he emphasized, were “not life-threatening” and “could be dealt with medically.”
But Lilly scientist Dr. David Goldstein, who has studied birth outcomes of women on Prozac and found no ill effects, said the San Diego researchers “overreached” and “made inferences that were not warranted by the data.” For instance, he said, babies born to women with severe depression are known to have more health problems than other babies, and the researchers did not take that fully into account.
He suggested that some women with serious depression might be harmed if they quit taking the drug. “I worry that if they’re not adequately treated they could rebound in their depression and become suicidal or take other medications that are really detrimental,” he said.
Adding to the controversy, an editorial in the New England Journal by Dr. Elisabeth Robert, a birth defects specialist at a research institute in Lyons, France, said the new research was inconclusive: “It seems unjustified to use these new results as a reason to withhold fluoxetine from women who require an antidepressant drug during pregnancy.”
In the new study, the researchers identified 228 women who were taking Prozac when they became pregnant. Some stopped taking the drug in the first trimester, some continued until delivery, and others were eventually disqualified from the analysis for various reasons, such as having a caesarean section. The researchers also tracked a control group of 254 pregnant women with roughly the same backgrounds who were not depressed and did not take Prozac.
Among the women who remained on Prozac throughout pregnancy, 14% of the births were premature, compared with 6% in the control group. Also, 32% of babies born to the drug-treated mothers were admitted to a special-care nursery for medical problems such as irritability, breathing trouble and low blood sugar. This compared to 9% of the controls.
Jones of UC San Diego suggested that some newborns may be experiencing some of the side effects known to occur in adults on Prozac, which include weight loss, anxiety and irritability in some patients.
But other researchers point out that because 30% of the women in the study on Prozac were also taking another antidepressant drug, some of the problems may have resulted from those other drugs, or from their interaction with Prozac. Also, smoking, which has been linked to newborn complications, was much more common among the Prozac-treated women than among the controls.
Jones said that researchers’ calculations attempted to balance out such factors, but critics were not satisfied. “One of the biggest flaws of the study was the lack of an appropriate control group,” such as women with serious depression who did not take Prozac, Lilly’s Goldstein said.
The San Diego study also turned up a higher-than-expected number of so-called minor anomalies among babies born to mothers on Prozac. Such anomalies include an extra tiny flap of skin around the eye or unusually small fingernails, said UC San Diego’s Christina Chambers. In fact, the researchers say, 16% of babies born to mothers who took the drug at any time during pregnancy had three or more such anomalies, compared with 7% among the controls.
Jones said that such clusters of minor physical anomalies often herald neurological problems that appear only later in a child’s life. “I think it’s a red flag,” he said of the observation, which his research team is studying in follow-up work.
Again, though, some researchers faulted that observation, saying that drugs that cause even minor physical defects prenatally tend to cause particular ones, and the San Diego researchers found no such patterns.
“I do not think that fluoxetine . . . [has] been clearly proved unsafe for pregnant women,” Lyons’ Robert concluded, “but [its] use involves a calculated risk because of uncertain side effects.”
