September 7, 2017

expert reaction to study looking at antidepressant use in pregnancy and psychiatric disorders in children

Scientists publishing in the BMJ report an association between antidepressant use in pregnancy and diagnosis of psychiatric disorders in children.

A Before the Headlines analysis accompanied this roundup.

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

“This new study makes use of large data obtained from Danish registries.  As with the other Scandinavian databases, these have provided a wealth of information on the epidemiology of mental illnesses.  This study reports that antidepressant use by women during pregnancy is associated with a small increased risk of mental health problems in their children.  This adds to previous research which has found 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 confounders.  In particular we know already that parental mental health can have impacts on a child’s development.  The authors have tried to control for this in a number of ways.  However, given that the types of medicines investigated in this study (commonly referred to as antidepressants) are also helpful in a range of illnesses in addition to depression, this adds an extra layer of complexity when trying to understand the results of this study.  This is because it remains possible that the increased risk of psychiatric disorder in children could be due to processes related to the illness rather than a direct effect of the medicines per se.  Along these lines, it is interesting that the use of these medicines by fathers during pregnancy is also associated with an increased risk of mental health problems in children and in this case direct effects of an antidepressant taken by the father on a baby in the uterus would be difficult to understand biologically.  Furthermore, future research is needed to control for the mental health of parents during their child’s development.

“As the authors point out, “discontinuing antidepressants… can lead to psychiatric episodes with subsequent long lasting adverse effects on both the mother and child”.  I agree and my advice in this regard remains unchanged.  As is the case with every medicine, mothers and their doctors will need to continue to weigh up the potential risks and benefits of taking these treatments 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 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 her 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 and other illnesses alongside other psychiatric treatments including cognitive-behavioural therapy and other types of psychotherapy.”

Dr Martin Ward-Platt, Consultant Paediatrician (Neonatal Medicine) and spokesperson for the Royal College of Paediatrics and Child Health, said:

“Although a significant sample size, the research has limitations in that it does not account for other important maternal factors such as alcohol intake, smoking, and the use of non-prescription or illicit drugs.

“Further confounding factors include an inability to clarify whether the results are due to genetic predisposition to mental illness among the children, or an outcome mediated by the impact of the mothers’ depressive illnesses on their relationships with their child during the crucial early postnatal years.

“It cannot therefore be definitively said that antidepressant exposure has a causal effect on the slight excess of later mental health problems in the offspring. However these are powerful drugs that could potentially affect fetal brain development, so it is important to investigate any possible unwanted side effects.

“The idea that mothers should avoid antidepressant drugs in pregnancy is not new, but must be weighed against the fact the in the UK the most common indirect cause of maternal death is suicide. Mothers’ mental health in the short term is important to ensuring a healthy, happy child in the long term.”

Prof. Rebecca Reynolds, Associate Member MRC Centre for Reproductive Health, University of Edinburgh, said:

“This is an important study addressing the potential consequences of exposure to antidepressants in the womb and offspring outcomes. We know that untreated depression can also have adverse consequences for the offspring and it is very difficult in these studies to dissect out the effects of the drugs as opposed to the underlying condition that they were being used to treat.

“Women with depression in pregnancy should seek healthcare professional advice to ensure that they are well during their pregnancy in order to have the best outcomes for them and their babies.”

Prof. Kamilla Miskowiak, Leader of the Neurocognition and Emotion in Affective Disorders (NEAD) Group, Department of Psychology, and Mental Health Services, University of Copenhagen, said:

“This is an interesting study in a large cohort. However, in this kind of study, confounding by indication is a key concern. That is, we cannot conclude based on these findings that antidepressant use during pregnancy is the cause of the slightly greater risk of psychiatric illness in the offspring. The women who use antidepressants before and during pregnancy are likely to have a more severe illness and greater genetic vulnerability – which is likely to contribute to the  higher risk in the children of these mothers. Indeed, a previous recent study in JAMA by Dr Vigod and colleagues showed that the association between use of antidepressants during pregnancy and autism in the offspring may not be direct but may be mediated by other factors.”

Prof. Carmine Pariante, Professor of Biological Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, said:

“This is an important paper, but it remains virtually impossible to fully disentangle the effects of antidepressants from the effects of the underlying mental disorders for which the drugs are prescribed.

“Many studies have found that untreated depression in pregnancy increases the risk of mothers drinking alcohol and smoking during pregnancy, seeking less antenatal care, and developing postnatal depression, as well as the risk of their offspring being exposed to a harsh childhood and developing mental disorders in adulthood. Based on this, the risk of discontinuing antidepressants in pregnancy, for mothers with moderate to severe depression, continues to outweigh the potential risk (if any) uniquely associated with antidepressants.

“Clinical guidelines already recommend a high threshold for prescribing antidepressants in pregnancy and the importance of an individualised discussion with mothers, and the authors rightly acknowledge that this paper does not change these recommendations.”

Prof. Michael Craig, Reader in Neurodevelopmental Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, said:

“We already know that mothers who are depressed or anxious in pregnancy give birth to children who are at risk of psychiatric problems in later life.  The underlying cause for this risk is probably complex. However, some scientists believe that this is directly due to the mother’s condition, and not necessarily due to effects of medication. If this view is correct then it suggests that in certain cases it would be advisable for mothers to take more medication, to robustly treat their condition, not less.

“It is not possible to work out whether the findings in the current study are due to medication or the mother’s underlying illness, or both.  Consequently, the management of women with mental health problems should not change and those that need medication during pregnancy should continue to be prescribed it.”

* ‘Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study’ by Xiaoqin Liu et al. published in the BMJ on Thursday 7 September 2017.

The SMC also produced a Factsheet on genome editing which is attached and available here: http://www.sciencemediacentre.org/antidepressants/ 

Declared interests

Dr Michael Bloomfield: “My full affiliations are: Clinical Lecturer in General Psychiatry and Honorary Senior Clinical Research Fellow, University College London and MRC London Insitute of Medical Sciences, and Scientific Advisory Panel Member, European College of Neuropsychopharmacology. 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. I have no other interests to declare.”

Prof. Kamilla Miskowiak: “I am a clinical psychologist and have no conflicts of interest. In the past, I have acted as a consultant for and received honoraria from Lundbeck and Allergan.”

Dr Martin Ward-Platt: “Martin is the unpaid chair of The Children’s Foundation, a charity supporting the prevention and management of mental health disorders in children.”

Prof. Carmine Pariante: “I have received research funding from pharmaceutical companies developing novel antidepressants, but not for research related to the perinatal period.”

None others received.