There is no evidence that GlaxoSmithKline’s widely-used antidepressant Seroxat/Paxil causes congenital abnormalities if taken by pregnant women, according to German researchers.

The US Food and Drug Administration added a warning to the labelling for Paxil (paroxetine) in October last year, saying the drug could increase the risk of major congenital abnormalities and should not be used in pregnant women, adding to the pressure on the drug which has also been linked to an increase in suicidal behaviour in children and adults. Around 25% of Paxil patients are women of child-bearing age, according to GSK.

But new evidence presented at the 22nd annual conference of the European Society of Human Reproduction and Embryology yesterday contradict the FDA’s findings, and highlight the need for international pharmacovigilance systems to be developed in order to provide better insight into potential risks of drugs given during pregnancy, say the researchers.

Dr Wolfgang Paulus, director of the Institute of Reproductive Toxicology at the University of Ulm, Germany, told a news briefing that the FDA warning “showed that the absolute rate of major congenital malformations seen in the first trimester for paroxetine users was 4%, and 2% for cardiovascular malformations.”

But results came from an unpublished, retrospective study of 5,956 women with 591 cases of medication with paroxetine during the first trimester and did not include controls of women not taking an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.”

The results indicated that the rate of congenital abnormalities was not increased after using paroxetine in early pregnancy. Moreover, the dataset also suggested that there was a higher tendency for women to decide to terminate their pregnancies in the paroxetine group, with 15% electing do so compared to less than 3% of the control group. Paulus said that a combination of depression and ‘confusion caused by information on possible damage to the foetus from the package labelling’ was responsible for the difference.

“Our results show the importance of a reliable pharmacovigilance 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,” said Paulus.

He also said there is an ethical imperative here, because patients may opt for termination of pregnancy due to fear of congenital malformations.

Meanwhile, 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.”