Antidepressants during pregnancy and autism – Expert Reaction

A new study in the BMJ found a small increase in the rate of autism in children whose mothers took antidepressants during pregnancy

The UK SMC prepared a ‘before the headlines’ analysis of the paper, along with expert reaction. The analysis, and the researchers themselves, highlighted the small increase in absolute risk: 95% of the women taking antidepressants during pregnancy did not go on to have a child with autism.

Writing on The Conversation, Helen Leonard from the Telethon Kids Institute said the paper attempted to answer a very important research question, but it was crucial that appropriate clinical management of depression during pregnancy was not compromised by the results. “Pregnant women experiencing depression should stick to their current management plan until we know more”.

The Australian and UK SMCs gathered expert reaction on the paper, feel free to use these comments in your reporting.

Assoc Prof Maree Hackett is the head of the mental health and chronic disease program at The George Institute for Global Health:

“We must be very careful when discussing observational research and whether study results can be applied to families who weren’t included in the study. Correlation (two things that happen at the same time) is not the same as causation (one event that causes a future event). Pregnant mothers, especially pregnant mothers with depression severe enough to need antidepressants, have enough to think about without anyone suggesting that their prescribed antidepressant medication might harm their unborn child. The only way to show a causal relationship between antidepressant use by women who are pregnant and a subsequent autism spectrum disorder in the child from that pregnancy, is by conducting a randomised controlled trial. These data are not from a randomised controlled trial. In this observational study two groups of pregnant women were compared: those who used antidepressants during their pregnancy, and those with any history of a psychiatric disorder who did not use antidepressants during their pregnancy.

“The two groups of women are not likely to be the similar and no amount of statistical analyses can compensate for the fact that the women using antidepressants were likely to have more severe depression (depression severity was not measured in the study) than women in the comparison group. Also, for those using antidepressants, their depression was most likely very recent. Those with a history of psychiatric disorder could have experienced that disorder at any age, well before the birth of their child. While this research has produced an interesting theory that could be benefit from further research, pregnant women who currently need to use antidepressants should continue to use them.”

Professor Andrew Whitehouse is head of the Developmental Disorders Research Group at the Telethon Kids Institute:

“This was a well-controlled, rigorous study that showed a very small increase in the likelihood of having a child with autism if a mother takes anti-depressant medication during pregnancy. Critically, the study cannot tell us whether this link is causal. The key issue for me is one of weighing up risk. Even if the very weak link proves to be causal – and that is a big ‘if’ – how does this weigh up against the very substantial challenge of untreated depression? At this stage, these findings are far too preliminary to have any implications in terms of recommendations to pregnant women. Management of mood disorders during pregnancy, a time of considerable life change, remains the key priority.”

Professor Anne Buist is Director of Women’s Mental Health at Austin Health – Northpark Private Hospital, and a Professor at the University of Melbourne:

“In advising women it is always a balance of risks – being unwell during pregnancy also is a risk to the foetus – these babies are at a higher risk of being born with altered stress responses, a likely marker for later mental health issues. The other thing important in the balance to consider is the dose of antidepressant and family history of autism.”

Professor Julie Quinlivan is a senior obstetrician with the Institute for Health Research at the University of Notre Dame Australia:

“This is an important study. Autism spectrum disorder has many multiple causes, but this study raises the concern that antidepressant medication may play a role is some cases. In pregnancy, antidepressant medication should be reserved for women with moderate to severe depression. Women with mild depression are ideally treated with psychotherapy or counselling. However, before ceasing treatment, pregnant women should discuss their situation with their treating specialist.”

Dr Jason Howitt is a Research Felllow at the Florey Institute of Neuroscience and Mental Health”

“The study by Rai et al. has investigated the risk of autism in the offspring of women who are prescribed antidepressants during pregnancy. This is an important issue given the large number of women diagnosed as having depression during pregnancy, and previous conflicting reports on the subject. Overall, by carefully studying a large population of women and their children, the authors have shown that there is a very minimal risk of antidepressants being causal for autism. Therefore, given the health consequences of untreated depression during pregnancy, this work indicates that, where appropriate, antidepressants should be used.

“This is one of the largest studies to investigate the role of antidepressant use and autism, but importantly it is quite well controlled for confounders, meaning that the control group and the drug treated group are closely matched for other factors that could also potentially cause autism. This is very important as without such careful analysis the results of many studies are called into question.

“The research relies on the excellent health care database collected in Sweden and, in my opinion, shows quite well that there is little to no association between antidepressant use in pregnant women and autism. This is an important finding and should allow pregnant women to make a better choice in treating depression when pregnant. It should be highlighted that a pregnant woman who responds well to antidepressant treatment will most likely have a healthy baby and avoid other health related problems that depression can cause.

“For Australian women who are struggling with depression during pregnancy they should speak with their doctor and understand that the best current research shows almost no association at all between antidepressant use and autism in offspring.”

Associate Professor Helen Leonard is Co-Head, Child Disability at Telethon Kids Institute:

“Mental illness occurs a little more commonly in the mothers and families of children with autism, as we and others have shown using population data linkage studies suggesting perhaps that genetic factors contribute to the risk of autism. Evidence for environmental factors such as the role of medication taken during pregnancy is also accumulating. This recent study used data linkage to investigate any relationship between the mother’s use of antidepressants during pregnancy and the development of autism in their child. It identified a very slightly increased risk for these mothers but also showed that more than 95 per cent of women who took antidepressants did not have a child with autism.”

Prof. Ian Jones, Professor of Psychiatry and Director of National Centre for Mental Health, Cardiff University, said:

“This paper adds to the existing literature that has found an association between exposure to antidepressant medication in pregnancy and a higher risk of autism in children. Consistent with previous studies the increase in risk is not large – in this study autism was found in around 4% of exposed children compared to around 3% in controls.

“It is possible that the higher risk of autism is due to the medication, but it may also be due to the effects of the mood disorder for which the medication has been prescribed. Given that family studies show increased rates of mood disorder in the parents of children with autism it is also possible that an overlap in genetic factors between mood disorders and ASDs is also involved.

“This study is also consistent with previous studies in finding that other factors found more commonly in women prescribed antidepressant medication may at least partly account for the increased risk. In the current paper, for example, psychiatric disorders in pregnancy that were not treated with antidepressants were also associated with an increased risk of autism. The paper attempts to control for these confounding factors in a number of ways and still finds an association – but it is not possible to rule out other factors that may differ between the groups that could not be controlled for.

“So where does that leave women and their clinicians making difficult decisions about medication at this time.  Although it is still difficult to know for definite whether antidepressant medication increases the risk of Autistic Spectrum Disorders in children, what we can be certain of is that any increase is not large. Depression in pregnancy and following childbirth (the postpartum period) is common, and is an illness with potentially serious consequences. It can be severe, with serious implications for the woman, her baby and her wider relationships. Suicide is a leading cause of maternal death in the UK.

“Women should not be taking medication in pregnancy if they don’t need to. For a woman taking an antidepressant and who is considering starting a family, or finds that she is pregnant, this is an excellent time to consider whether the medication is still required. Women should not stop their medication suddenly and, if they are concerned about continuing the antidepressant in pregnancy, they should discuss the options with their doctor.

“For some women, episodes of depression may be mild and brief, while in others they may be very severe and long lasting. A range of different treatment approaches may help women with depression and may include improved support, specific psychological and social interventions and for some women treatment with medication. In general the National Institute for Health and Care Excellence (NICE) only recommends antidepressant treatment for people with moderate to severe episodes of depression. It is vital that women who become depressed in pregnancy can access appropriate and timely help. For some women with moderate to severe episodes of depression, or with a history of severe mental illness, taking medication in pregnancy may be the most appropriate decision.

“The decision to take medication in pregnancy is always difficult. It must be made by women themselves, following discussion with their doctors where they weigh up the risks and benefits of all options, taking into account their individual needs and circumstances. It is important to recognise that severe psychiatric illness may have negative consequences for the woman, her baby and her family, and these must be weighed against what is known about the risks of taking medication.”

Dr Michael Craig, Senior Lecturer in Reproductive & Developmental Psychiatry, KCL, said:

“It is important to make clear that these results are not conclusive and the effect size of SSRI medication on the risk for Autism Spectrum Disorders (ASD) is very small. However, these results cannot be ignored and if the link between SSRIs and ASD is found to be robust then it raises several important issues.

“Firstly, this study was unable to assess trimester effects. It might, for example, be safer to take SSRIs after the first trimester and avoidance of SSRIs in later pregnancy might be safe.

“Secondly, it is unclear whether other, non-SSRI, antidepressants (e.g. Agomelatine) might be safer in pregnancy.

“Thirdly, this study highlights the need to further research into non-pharmacological methods of treating depression in pregnancy such as repetitive Transcranial Magnetic Stimulation. In December 2015 NICE reported that ‘Transcranial magnetic stimulation for depression is safe enough and works well enough for use in the NHS’. However, provision of such treatment in the NHS is sadly still lacking.”

Dr Michael Bloomfield, Clinical Lecturer in Psychiatry, UCL, said:

“This new large and well conducted study by an internationally respected team of epidemiologists reports that antidepressant use by women during pregnancy is associated with a small increased risk of autism in their children.  Previous studies have reported this association, however association is not the same as causation as there could be host of possible alternative explanations for why two events appear to be associated with each other, called confounds.  This is especially challenging when scientists and doctors need to rely on observational studies to answer particular types of medical research question, as is the case here. In particular, we know that mental well-being in parents is associated with improved outcomes for their children.

“In order to try and get round this the authors have used different approaches to analysing the same data to take these confounds into account.  These different approaches produce results that agree with each other which adds weight to the association between antidepressant use and the small increased risk of autism in children.   Nonetheless, as the authors of this study themselves point out it still remains possible that this finding is not due to a direct effect of antidepressant medicines.  Much more research is needed into what causes autism and related conditions before we can say with certainty whether or not antidepressants are directly responsible.  In parallel, research will be continuing in order to establish which medicines appear to be associated with the safest outcomes for mothers and their children during pregnancy.

“For now, as is the case with every medicine, mothers and doctors will need to continue to weigh up the potential risks and benefits of taking antidepressants during pregnancy.  Approximately 1 in 10 pregnant women will experience depression in pregnancy.  Whilst common, depression in pregnancy is associated with a number of risks to both a mother and her baby.  In more severe cases depression in pregnancy can be a potentially serious and life-threatening and so any pregnant mother experiencing depression should seek appropriate help from her doctor and not stop taking antidepressant medicines without first discussing it with their GP or psychiatrist.  Important factors to consider will include whether a mother has experienced previous episodes of a mental illness and how severe these previous episodes have been.  Mothers must also remember that antidepressant medicines are only one part of getting better from depression alongside other psychiatric treatments including cognitive-behavioural therapy and other types of psychotherapy.”

Dr James Cusack, Director of Science, Autistica, said:

“Pregnant mothers using anti-depressants should not be concerned by these results. This well designed study suggests that mothers who have psychiatric conditions are more likely to have children with autism. It was also found that anti-depressant use in pregnancy is associated with a very slight increase in the likelihood of autism.  Previous studies find that anti-depressants do not cause autism and that any link can be explained by factors such as the mother’s genetics and increased severity of depression. It seems likely that the link in this study can be explained by the same factors.

“This study is strengthened by the use of a large health records database which covers the whole of Sweden.  Unfortunately the analysis is limited by the amount of data available which means that it cannot explain why an association exists. For that reason the study can only demonstrate an association, it cannot explain the underlying cause of the association.”

Dr Max Davie, Mental Health Lead, Royal College of Paediatrics and Child Health (RCPCH), & Consultant Community Paediatrician, Evelina London Children’s Hospital, said:

“As the researchers themselves state, ‘it is impossible to dismiss the possibility that observed associations are wholly attributable to confounding’. This is particularly true because they have not controlled their results for the severity of maternal depression. In essence they are therefore comparing women sufficiently depressed to require treatment with all women with any history of mental health problems, and so an effect as small as the one found seems likely to be due to this confounding factor rather than the mooted pharmacological effect of anti-depressants.

“There is no reason on the basis of this data for women to alter their decision-making when it comes to the choice of treatment for depression in pregnancy.”

Dr Christoph Lees, Clinical Reader in Obstetrics, Imperial College London, said:

“The authors of this interesting paper are right to be cautious about their results. If there is indeed a causal relationship between antidepressants and autism it is a very modest one. Though various statistical methods were used to adjust for confounders, women on antidepressants had more specialist care, more episodes of depression and used other therapeutic drugs more frequently. They may not be comparable to those not taking antidepressants.

“So it is possible that factors other than antidepressants explain the relationship seen with autism. In other words this study raises important questions but does not prove that antidepressants cause autism.”