July 8, 2015

expert reaction to study on antidepressant use in early pregnancy and risk of birth defects

The use of pharmaceutical drugs during pregnancy is an area of controversy, and a possible association between the use of certain antidepressants early in pregnancy and birth defects is the subject of a paper published in The BMJ. The authors report no association for some of the drugs that they tested, but an increased risk when using two specific selective serotonin reuptake inhibitors (SSRIs).

Dr Patrick O’Brien, spokesperson for the Royal College of Obstetricians and Gynaecologists (RCOG) said:

“This study examines a possible link between 14 different types of birth defects such as anencephaly or atrial septal defects (hole in the heart) and SSRI use in the first few months of pregnancy. Although this is a large study involving more than 27,000 pregnancies, only about 1000 women had taken SSRIs. The results were then combined with results from other centres to provide a more robust analysis.

“The findings are reassuring as they confirm previous studies which suggest that SSRIs have a very low risk of causing birth defects. Of the five SSRIs investigated only two – Paxil (paroxetine) and Prozac (fluoxetine) – were found to have any increase in risk.  Even for these the absolute risk remains very low.

“Depression in pregnancy can be very serious for a woman and can also impact on the health of her baby, so we must consider the benefits of antidepressant medication in such cases. Our advice for pregnant women suffering with depression would be that generally the benefits outweigh the risks, however, all pros and cons should be discussed and weighed up by a woman, together with her obstetrician.”

Prof. Jean Golding, Emeritus Professor of Paediatric and Perinatal Epidemiology, said:

“This is a very large study on the face of it, but when divided into specific birth defects the numbers are small. Consequently the few statistically significant findings that there are may well have arisen by chance. More importantly the authors do not confirm a number of relationships between SSRIs and birth defects that have been reported previously.

“From this evidence I would conclude that if a woman really needs an SSRI, then she can be assured that the evidence implicating birth defects is slender. However it is always better not to take any medications in pregnancy if at all possible.”

Prof. Eduard Vieta, Treasurer and Chair of Communications Committee, European College of Neuropsychopharmacology (ECNP), and Professor of Psychiatry, University of Barcelona, said:

“What is new from this report is that previously reported birth defects that were attributed to sertraline were ruled out in this study.

“The study supports previous findings related to paroxetine and fluoxetine, but odds ratios are very low and may be unstable due to the small number of events. The main limitation is the potential confounding by indication, meaning that it is unclear whether the drug or the underlying condition (depression and other conditions that are commonly treated with SSRIs) is causing the risk. Hence, the main conclusion that I take is that some of the reported risks connecting birth defects and SSRIs are scientifically weak and studies like this one prove that when large numbers of patients treated with one drug are considered (such as in this case with  sertraline), previous findings are often unreplicated.

“Nevertheless, a careful assessment of pros and cons of SSRIs prescription in early pregnant women is necessary and patients should be informed of the potential risks of treating and not treating their underlying condition with such therapy.”

Dr Michael Bloomfield, Clinical Lecturer in Psychiatry, MRC Clinical Sciences Centre and University College London, said:

“Serotonin reuptake inhibitors (SSRIs) are widely used medicines in the treatment of a range of mental illnesses including depression, anxiety disorders and obsessive-compulsive disorder.  It has been known for some time that there is a small increase in the risk of birth defects when women take these medicines in pregnancy, although some of these medicines appear to be safer than others.

“This new study provides further data on the risk of birth defects associated with serotonin reuptake inhibitors when used in pregnancy. In particular, this study provides further evidence that will guide doctors in deciding with their patients which specific types of serotonin reuptake inhibitors may be safer than others. As the incidence of birth defects remain rare occurrences, future studies will benefit from including larger sample sizes across different countries.

“The ways in which these drugs might potentially increase the risk of these birth defects needs further study. Likewise, further research is needed to explore whether the dose of particular treatments is associated with increased risk or not. This is important because generally speaking doctors in the United Kingdom have tended to prescribe lower doses of psychiatric medicines than in the United States of America, where this new study took place.

“Whilst common, depression can be a potentially life-threatening illness. Any decision around treatment in pregnancy needs to weigh up the potential small risks of birth defects against the benefits of treatments including helping a mother get better from depression. In addition, there is evidence to suggest that a baby whose mother had depression during pregnancy  may be more likely to have mental illnesses themselves during later life. Any woman who is either pregnant or planning to become pregnant and needs to take a serotonin reuptake inhibitor should discuss her treatment with her GP or psychiatrist. It may be that they advise switching to a different serotonin reuptake inhibitor that appears to be safer. No one should stop taking a serotonin reuptake inhibitor without first discussing this with their doctor.”

‘Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports’ by Reefhuis et al. published in The BMJ on Wednesday 8th July. 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/?s=antidepressants&cat