Study contradicts USA warning that an antidepressant can cause congenital abnormalities

A study carried out by German researchers has failed to show that a popular antidepressant, paroxetine, causes congenital abnormalities if taken by pregnant women, the 22nd annual conference of the European Society of Human Reproduction and Embryology heard.

Dr Wolfgang Paulus said the results were important because they contradicted a warning issued by the US Food and Drug Administration in October 2005 that the use of paroxetine (brand names: Seroxat, Paxil, Aropax, Deroxat or Pondera) could increase the risk of major congenital abnormalities. The warning may have caused women to terminate their pregnancies unnecessarily.

Dr Paulus, director of the Institute of Reproductive Toxicology at the University of Ulm, Germany, told a news briefing: "Our results show the importance of a reliable pharmaco-vigilance system documenting foetal outcome after medication in pregnancy. We need international networks of registries to do this, but financial support for this purpose is lacking. We hope for more serious efforts from the pharmaceutical industry and governmental authorities in Europe. We think that this is also an ethical challenge because many patients opt for termination of pregnancy due to fear of congenital malformations.

The FDA warning about the drug, which is a selective serotonin reuptake inhibitor (SSRI), was issued on the basis of unpublished research. "It showed that the absolute rate of major congenital malformations seen in the first trimester for paroxetine users was 4%, and 2% for cardiovascular malformations. Yet the retrospective study of 5,956 women by the producer, GlaxoSmithKline, had only 591 cases of medication with paroxetine during the first trimester and did not include controls of women not taking an antidepressant," he said.*

In contrast, the research carried out by Dr Paulus and his colleagues was a prospective follow-up study that collected data on pregnancy outcomes after medication with paroxetine in 119 women between 1990 and 2005. "Our national Teratology Information Service (TIS) was contacted by physicians and patients after exposure to paroxetine in the first trimester of pregnancy. We compared the results with a control group of 645 women over the same period of time, who had not been exposed, or not severely exposed, to the drug.

"We found that the rate of congenital abnormalities was not increased after using paroxetine in early pregnancy. Three abnormalities were reported after exposure to paroxetine: club feet after exposure throughout pregnancy, a large port wine mark after exposure up to the seventh week, and spastic torticollis (painful spasms of the neck muscles) after exposure in the first twelve weeks. However, in the non-paroxetine group there was a similar rate of abnormalities, with 25 out of 557 babies affected."

However, the researchers did find that the number of women deciding to terminate their pregnancies was much higher amongst the paroxetine group. "Eighteen out of 119 paroxetine users (just over 15%) preferred termination of pregnancy compared to 17 out of 645 women in the control group (2.6%). In most cases the patients opted for termination of pregnancy because of a combination of reasons: partly because of their depression, but also because of confusion caused by information on possible damage to the foetus from the package labelling.

"Our prospective controlled follow-up study does not support the assumption that paroxetine can cause congenital abnormalities. Although our study of 119 paroxetine users was relatively small, there are three other, peer-reviewed, published studies that show no increased rates of cardiovascular malformations with paroxetine, whereas there has been no published research that shows that paroxetine can cause abnormalities. We continue collecting data as a member of the European Network of Teratology Services (ENTIS) in order to reassure patients who need a long-term antidepressant medication."

Dr Paulus highlighted the damage that incomplete research can have not only on the unborn babies, through decisions to terminate pregnancies, but also on the mental and physical well-being of mothers, through not treating their depression or stopping their medication abruptly.

"Depression, anxiety, obsessive-compulsive disorder and premenstrual stress are common disorders during child-bearing years and can be treated with antidepressants such as paroxetine. Failure to treat depression during pregnancy can have significant negative ramifications for both mother and child. Women and their physicians should discuss this information and make an informed decision, whether or not to continue with paroxetine during pregnancy. Concerned patients can be offered ultrasound and echocardiogram, which can rule out foetal cardiac problems in early pregnancy. Antidepressants should never be stopped abruptly as this can have serious ramifications for the mother. If a woman does decide, following a discussion with her physician, that she wants to discontinue paroxetine, the drug should be slowly tapered off."