The headlines are screaming again, ANTIDEPRESSANTS CAUSE AUTISM !!!!!!!!!!!!! (approximate average number of exclamation marks per article). Of course, a critical analysis of the the underlying study that caused the headlines is more nuanced and may not say what you think it says.
Autism spectrum disorder is a complex range of conditions classified as neurodevelopmental disorders by the American Psychiatric Association, which is described in detail in the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5).
The DSM-5 redefined autism spectrum disorder to encompass diagnoses of autism, Asperger syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), and childhood disintegrative disorder. Generally, symptoms of these disorders include social deficits and communication difficulties, stereotyped or repetitive behaviors and interests, sensory issues, and in some cases, cognitive delays.
The scientific consensus for the causes of autism has centered on genetic factors, generally several genes. This hasn’t stopped a whole host of claims as to what causes autism. Emily Willingham wrote an article a few years ago with the title, This just in: Being alive linked to autism, in which she lists 30 recent claims of what causes autism. It would be funny, if it weren’t so sad.
Of course, we cannot overlook the old canard that vaccines cause autism. Which is about as untrue as a claim can be in science.
So what about this new claim about antidepressants and autism spectrum disorder? It’s based on a study just published in JAMA Pediatrics, a relatively high impact factor (approximately 7.148) and selective peer-reviewed journal.
The results from the may be significant, but possibly a critical analysis of the article will give us a different perspective.
Antidepressants cause autism – the study
At the top level, the study appears to be one of the better ones out there, with lots of large numbers. That gives it a significant amount of power, from a statistics viewpoint.
The researchers, T Boukhris et al. from several institutions in Montréal, Quebec, followed over 145,000 full-term infants (all single births) for a total of over 900,000 person years of follow-up. That is massive relative to many epidemiological studies. Moreover, in a country with centralized coordination of medical care, there can be substantially large amount of information that can be gathered from medical records with just a few clicks on the computer keyboard – of course, I’m oversimplifying, but it is much easier than the mostly decentralized system in the USA, which makes epidemiological studies nearly impossible.
The study itself attempted to examine the association between the use of antidepressants during pregnancy, and then determine the level of risk of ASD.
So what did the researchers find? Well, if you read the popular press, you’d see statements along the line that the antidepressants cause an increase in autism by 87%. A result like that would be horrifying, and the FDA would issue black box warnings for every anti-depressant on the market contraindicating them for use with pregnant women.
But that’s not what the results actually said. The results showed an absolute risk of 0.87%, and increase risk of autism in children from approximately 1% for mothers who did not take anti-depressants to 1.87% for those who did. From a clinical point of view, those numbers may not be all that significant.
If the 87% increased risk was actually true, that would mean that the risk of autism with antidepressants would be around 88%, which would be a shocking number.
The results were even more complicated by the fact that there was no observed risk increase for exposure to anti-depressants during the first trimester or for the 12 months prior to getting pregnant. The only risk increase was shown for exposure to the drugs during the second and third trimester.
There have been other studies that have attempted to show that antidepressants cause autism – many had results similar to the this study. But a review of the data has shown that there is a lot of variability in and quality of results, which may (or may not) support the results of the study discussed herein.
And just to avoid cherry picking, there are even large studies that contradict this one, and claim that there is no link between anti-depressants and autism. In other words, there really isn’t a consensus about autism and antidepressants, something that’s not being said in the scare headlines recently.
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Aside from the general lack of consensus that antidepressants cause autism – I could cherry pick a study to show just about any point of view – I have a few issues with this study, although they may not be important, depending on your own perspective:
- The researchers were unable to determine whether the pregnant mothers actually took the medication – they only could track whether or not the mother got a prescription and filled it. Patient resistance to taking antidepressants can be quite high, so this may have confounded the results.
- There are standard warnings about antidepressants being taken by pregnant women. The FDA considers most antidepressants to be Category C drugs for pregnant mothers, that is, “Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.” This probably means that these medications are only prescribed when it’s clear that the benefits outweigh the risks.
- There are some studies, including this one, that have shown depression, including major depressive disorder and bipolar disorder, during pregnancy itself may be a cause of autism. But there’s far from a consensus on this either.
One of the aspects of evidence-based (or more strictly, science-based) medicine is that all of the evidence is weighted, according to quality and quantity, to determine the most effective course of treatment of any patient. And sometimes that treatment must weigh the benefits along with the risks. That equation may not be readily apparently.
The study wasn’t powered to tell us what the risks of a pregnant mother who has some sort of depression disorder who is not properly medicated. Depression can lead to higher risks of suicide, eating disorders, significant weight loss or gain, and other issues. A pregnant mother who has bipolar disorder may engage in risky behaviors that could harm the fetus. Finally, depressed and pregnant mothers may ignore proper prenatal care, despite their best intentions.
Furthermore, pregnant mothers who see the headlines splashed across the internet, and suddenly stop taking their medication. In many instances, that’s very dangerous, which can lead to suicide or deeper depression.
Let me make this one point, being one of the most important I’ve ever written here. If you’re pregnant, or you know someone who is, and you or they are taking antidepressants, and you read this article…stop. Take a deep breath. If you think that the risk of autism is too high, a valid concern, speak to your medical professional who prescribed the anti-depressants. Talk to them with honesty about your concerns. And if you all agree to stop the antidepressants, then do it carefully, so that you don’t put yourself, or the developing fetus, at risk.
Steven Novella wrote an article about this same study, and emphasizes the same points that I do:
[infobox]As with all of medicine, decisions consider risk vs benefit (including the risk of not doing something). In this case pregnant women and their doctors need to consider the overall risk of not treating depression with medication vs the modest increased risk from the medication. For mild depression the risks of medication are probably not worth it, but for severe depression it probably is. Where to draw the line is a judgement call.
I do hope the reporting of this study does not cause pregnant women suffering from depression to stop their medication without consulting their doctors. The decision should be made with a full understanding of the risks on both sides.[/infobox]
Please be careful out there.
- Boukhris T, Sheehy O, Mottron L, Bérard A. Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children. JAMA Pediatr. 2015 Dec 14:1-8. doi: 10.1001/jamapediatrics.2015.3356. [Epub ahead of print] PubMed PMID: 26660917.
- Chaste P, Leboyer M. Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci. 2012 Sep;14(3):281-92. Review. PubMed PMID: 23226953; PubMed Central PMCID: PMC3513682.
- Clements CC, Castro VM, Blumenthal SR, Rosenfield HR, Murphy SN, Fava M, Erb JL, Churchill SE, Kaimal AJ, Doyle AE, Robinson EB, Smoller JW, Kohane IS, Perlis RH. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Mol Psychiatry. 2015 Jun;20(6):727-34. doi: 10.1038/mp.2014.90. Epub 2014 Aug 26. PubMed PMID: 25155880; PubMed Central PMCID: PMC4427538.
- Morgan VA, Croft ML, Valuri GM, Zubrick SR, Bower C, McNeil TF, Jablensky AV. Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression. Br J Psychiatry. 2012 Apr;200(4):282-9. doi: 10.1192/bjp.bp.111.093070. Epub 2012 Jan 12. PubMed PMID: 22241931.
- Robinson GE. Controversies about the use of antidepressants in pregnancy. J Nerv Ment Dis. 2015 Mar;203(3):159-63. doi: 10.1097/NMD.0000000000000256. Review. PubMed PMID: 25714252.