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expert reaction to study reporting an association between antidepressants in pregnancy and autism in children

New research published in the BMJ studies the association between antidepressant use during pregnancy and autism.

A Before the Headlines analysis accompanied this roundup.

 

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.”

 

* ‘Antidepressants during pregnancy and autism in offspring: population based cohort study’ by Rai et al. published in The BMJ on Wednesday 19th July. 

 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/autism/

http://www.sciencemediacentre.org/?s=antidepressants&cat

 

 

Declared interests

Prof. Ian Jones: No conflicts of interest.

Dr Michael Craig: “I have been involved in setting up an rTMS Centre at the Nightingale Hospital in the Independent Sector. I am currently PI on a study designed to assess the feasibility of rTMS in pregnancy in the NHS.”

Dr Michael Bloomfield: “I am a member of the Royal College of Psychiatrists, a member of the British Association of Psychopharmacology, a young member of the European College of Neuropsychopharmacology, a young fellow of the Royal Society of Medicine and an international member of the American Psychiatric Association. I conduct research funded by the Medical Research Council, the National Institute of Health Research and the British Medical Association. I work in medical research at the Medical Research Council and University College London. I work clinically in the National Health Service. One of the paper authors is the head of department where I work at UCL. I have no other interests to declare.”

Dr James Cusack: No conflicts of interest

Dr Max Davies: No conflicts of interest

Dr Christoph Lee: No conflicts of interest to declare

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