Five years ago, the Croen et al article in the Figure above appeared suggesting that antidepressant use in pregnancy can cause Autistic Spectrum Disorder (ASD). Pharmaceutical companies rushed to manage the risks – to them.
What you do is you convene your experts and you put them in boxes, a teratology box, an animal studies box, an epidemiology box, a psychology box, a pharmacology box and other boxes and you make sure none of the boxes can communicate with each other. You ask the experts in each box to tell you whether the evidence from their area alone demonstrates conclusively that your drug causes ASD – you make sure they hear the question clearly – it’s your drug not all SSRIs or all antidepressants.
So each group reports back to the person managing the process, who for the sake of objectivity is not an expert in any of these areas, that no there is no conclusive evidence from their little box that our drug causes ASD. Cause here is code for the fact we can fight this in court.
For those not conversant with the data, the epidemiological studies in the figure above show conclusively a link between SSRI use and ASD.
If the person coordinating the process is asked whether she got her hermetically sealed experts to review all studies pointing to Neurodevelopmental Delay of one sort or another, she will almost certainly say no she didn’t, that her brief was to get the groups to review studies that have the words Autistic Spectrum Disorders (ASD) in their title or abstract. If asked the question, do you not think that that ASD is pretty well another word for neurodevelopmental delay, she will say she has no idea, she knows nothing about this. The brief was just to consider articles with ASD in the title or abstract.
Far-fetched? Absolutely not. This is standard company MO when faced with an adverse effect. It’s about being objective. We want to find what is absolutely established without letting personal views get in the way. It would be irresponsible to our shareholders, and any of you who have your pensions invested in our company, to do anything else. Sounds good – no one wants to lose their pension over a media scare story. But the same kind of thinking underpins Holocaust Denialism.
Here is what the Neurodevelopmental Delay studies look like.
For those of you not conversant with Figures like this, the data show SSRIs cause Neurodevelopmental Delay.
So do SSRIs cause Autistic Spectrum Disorder? The first thing to say is that ASD is fuzzy. People contact me who are politicians, or working in the caring professions, wondering if they have ASD. Almost by definition they don’t if they are interacting effectively with people. But we seem to be in a time when the normal variation that exists between all of us is at risk of getting recategorized as a disorder if we do not appear to be exactly the same as some notional average man or woman. Plus we live in a world of horoscope medicine where fuzzy criteria are worded so that it’s easy to figure they apply to you.
That said, what these figures show is that pretty well whatever we dump into the ASD diagnostic basket, SSRIs increase it. The latest study not yet included in the table above shows reduced rates of verbal fluency and disordered communication styles caused it seems by SSRIs. These difficulties are linked to ASD.
For SSRI usage to have played a part in increasing rates of ASD, we would expect there to be evidence that there has likely been an increase in the use of these drugs in women of child-bearing years and a more relaxed medical and public attitude about the use of these drugs during pregnancy.
For antidepressants before the SSRIs, the market was largely in older age groups. For the SSRIs, for whom the marketing mission was to persuade cases of Valium they were really cases of Prozac or Seroxat or Zoloft, it was clear that a large part of the market would be to women of child-bearing years.
In the early 1990s when the SSRIs were marketed first, the prevailing wisdom was that giving psychotropic drugs in pregnancy was to be avoided; regulators supported avoidance , professional bodies supported avoidance , and leading psychiatrists warned of the teratogenic potential of psychotropic drugs [121-123].
There was not thought to be any increase in the incidence of mood disorder during pregnancy . There was not thought to be any risk from mood disorders to the fetus; the risk from mood disorders lay in the risk posed to the mother such as suicide .
In contrast today when Antidepressants are the most commonly used drugs in pregnancy, it is common to hear claims that depression directly or indirectly causes birth defects; to see depressive symptoms regarded as depressive illnesses, so that rates of 15-20% for depressive disorders are cited when this should only apply to depressive symptoms ; and it is not widely noted that the majority of states treated with these drugs left untreated clear up spontaneously within weeks.
In 2015, in the absence of any intervening data that depression causes birth defects or that SSRIs are effective in antenatal depression, the exact same authors who advocated caution before the marketing of the SSRIs can be found supporting claims that:
If SSRIs work, as claimed by marketing, namely by correcting a serotonergic abnormality it might be thought they would reduce the risk of things going wrong. But there is no such abnormality and treatment with an SSRI on balance will leave serotonin systems more abnormal than they were to begin with .
If working means that SSRIs reduce risky behaviors including alcohol and drug intake, the evidence is the opposite; SSRIs increase alcohol and drug use and risky behaviors [131,84].
For anyone who wants to check out the references listed here, they can be found HERE.
Anyone who is concerned about a link between SSRIs and ASD will be faced with the following counter arguments.
First, rates of ASD from these studies, as is the case with rates of birth defects on SSRIs, fall within the background rate of the population at large and on this basis it is claimed that even where the rates in the treated group exceed those in the control group, these rates can be discounted [see 132,128]. This argument is not valid for birth defect studies where the background rate is determined by the study design. The argument is even more misplaced for a condition like ASD or neurodevelopmental spectrum disorders where the background rate appears to be changing by the year.
Second, studies of SSRI use during pregnancy show a consistent rate of problems and that when all studies are meta-analyzed the risks disappear. We have not been able to analyze all studies as some groups, such as the Motherisk group, refuse to share their data. [This was written before the Motherisk group, which had close links with Pharma, imploded, and its director Gideon Koren has vanished.]
Third, it is claimed that depression causes both birth defects and ASD and is endemic in pregnant women at rates of 15-20%. There is no good evidence for these propositions. These claims are from the Donald Trump – Josef Goebbels school of propaganda. [Although it should be noted that the Nazis did good things like try to ban smoking before anyone else and Trump has proposed some useful things too where Clinton has advocated a problematic increase in screening].
Fourth, it is proposed that there are no adequate and well-conducted studies in this area. This statement means that there are no RCTs and assumes the reader will accept the proposition that only RCTs can demonstrate whether an antidepressant causes birth defects or ASD or not. This is just plain wrong. RCTs can get the answer as badly wrong as any other epidemiological study [see 133]. They can easily be gamed to get the wrong answer. To establish what is happening will need judgments that take both epidemiological and biological data into account. It is only when there is a good understanding of what is happening that an appropriate RCT can be designed, and might be useful to confirm (not prove) what is already known.
Finally, it is claimed that the results cited from a majority of studies show no statistically significant difference between women treated and those not treated. For some, if an increase in risk is not significant, they take a view that there is in fact no increase in risk. Other than when it comes to questions about the use of drugs in medicine, there is nowhere else in science that this view has any credibility . The visual plots of the meta-analyses demonstrate the flaws in this argument.
All references to these points can be found in the article above.
BMJ Open refused to take this article because the review covered everything – both human and animal studies – and BMJ only take human studies. They are a human box only journal.
The Brown et al study showing SSRIs causing Neurodevelopmental delay, also available above, that has just appeared has been difficult to access in JAMA Psychiatry but a critique of it by Lee Cohen – one of those who once advocated caution about the use of antidepressants in pregnancy has been readily available. What does Cohen find wrong with the Brown study? It’s not an RCT etc – see points 1-5 in the coda.