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Without a doubt, they’re two of today’s most alarming health trends:

These two megatrends intersect, researchers say, when pregnant women are treated for depression, anxiety and other maladies with antidepressants.

Indeed, multiple studies conducted over several years now lead research scientists to conclude that women taking any brand of modern antidepressants – commonly called “SSRIs” (selective serotonin reuptake inhibitors) – while pregnant run an increased risk of giving birth to a child with an autism spectrum disorder.

Yet, the public – most importantly, the tens of millions of American women currently taking antidepressants, including 7-13 percent of all pregnant women – strangely has heard very little about this research and its important implications.

Why would that be? Let’s find out.

’4 times as likely to develop autism’

Two-and-a-half years ago, a groundbreaking peer-reviewed study out of California-based Kaiser Permanente documented a significantly increased prevalence of children born with autism spectrum disorders in pregnant mothers taking antidepressants, especially during the first trimester, compared with mothers not taking such medications.

And yet, the obvious implication of such a study – that pregnant women should probably avoid taking antidepressants – was all but neutralized by two factors: 1) It was the first human study, which understandably led the lead researcher, Kaiser Permanente’s Dr. Lisa Croen, to say more studies were needed to confirm the findings; and 2) most news organizations strongly skewed their coverage toward urging pregnant women to continue “taking their meds” despite the newly reported dangers to their unborn children.

For example, CNN’s story, “Are antidepressants linked to autism?,” started off reasonably enough:

Children whose mothers take Zoloft, Prozac, or similar antidepressants during pregnancy are twice as likely as other children to have a diagnosis of autism or a related disorder, according to a small new study, the first to examine the relationship between antidepressants and autism risk.

This class of antidepressants, known as selective serotonin reuptake inhibitors (SSRIs), may be especially risky early on in a pregnancy, the study suggests. Children who were exposed to the drugs during the first trimester were nearly four times as likely to develop an autism spectrum disorder (ASD) compared with unexposed children …

After this quick summary, however, the next five paragraphs of CNN’s report – like virtually all other big-media news accounts – focused on minimizing or undermining the study’s impact:

The study included fewer than 300 children with a diagnosed ASD and does not prove that taking SSRIs during pregnancy directly causes ASDs, which affect approximately 1 percent of children in the U.S. The findings will need to be confirmed in larger studies, and should not dissuade women from starting or continuing to take SSRIs, experts on prenatal drug exposure and mental health say.

“Poor maternal mental health during pregnancy is a major public health issue,” says Tim Oberlander, M.D., a professor of developmental pediatrics at the University of British Columbia, in Vancouver. “Nontreatment is not an option. While some children might be at risk from an SSRI exposure – and we don’t know who, and how that works – there are many mothers and their children as well who will benefit.”

The lead author of the study, Lisa Croen, Ph.D., the director of autism research at Kaiser Permanente Northern California, a large nonprofit health plan based in Oakland, emphasizes the preliminary nature of her team’s findings. “This is the first study of its kind to look at the association, and the findings have to be interpreted with a lot of caution,” she says. “We can’t detect causality from one study.”

Untreated depression during pregnancy carries its own risks, such as preterm birth and growth problems, Croen adds, and “the potential risks to the child really have to be balanced with the risk to the untreated mom. We don’t want people to rush off and stop taking antidepressants if they’re on them. They really need to talk to their doctors about the risk-benefit ratio.”

Max Wiznitzer, M.D., a pediatric neurologist at Rainbow Babies & Children’s Hospital and an associate professor of pediatric neurology at Case Western Reserve University School of Medicine, both in Cleveland, says the study is too small to draw any conclusions. The study is a “signal,” he says, “but with a really small group.”

By this time, most readers are reassured they should “stay on their meds” and that “more studies are needed.” OK, so where are they?

I recently asked Dr. Croen whether, since the public release of the 2011 study, her research team or others had delved further into the antidepressant-autism link.

“Since my article was published, there have been at least two publications that reported similar findings” corroborating the troubling antidepressant-autism link, Croen told me. “There are also other groups looking at this question and finding the same association.”

The plot thickens.

‘Trying to hide the problem’

The next – and larger – study was conducted in Sweden and released in April 2013.

“In our study,” the researchers concluded, “we found that mothers of children with autism were over 3-fold more likely to have reported using antidepressants during their first antenatal [pre- birth] interview than mothers of children without autism.”

The report’s bottom line: “In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability.”

That’s a second study essentially confirming the findings of the first. So, where was the media coverage?

There wasn’t any.

Well, there was one very nice – and refreshingly balanced – “parenting blog” published online by the New York Times, headlined “Study Links Autism With Antidepressant Use During Pregnancy.” But that was pretty much it. With one in 50 American school kids reportedly diagnosed with autism, and something like one in 10 pregnant woman taking the suspected antidepressant drugs, virtually no other major media organization found this study newsworthy.

Then there was yet another study of possible linkage, conducted in Denmark and released just this past November.

Similar to the other two studies, the Danish researchers discovered, as they explained in their report’s main analysis section: “Children exposed to any kind of antidepressant during pregnancy had a 50% higher risk for ASD [autism spectrum disorders] … compared with those not exposed.”

However, when the Danish researchers then “controlled” for a variety of “confounding factors” (a standard statistical discipline for interpreting raw data), the remaining increased autism risk was somehow deemed “not significant.” (Moreover, a second Danish study, which analyzed the exact same Danish database as the first study and was released about the same time, arrived at – no surprise – the same conclusion as the first Danish study.)

I reached out to Dr. David Healy – a U.K.-based psychiatrist, psycho-pharmacologist and expert on antidepressants and other psyche meds – to explain how an initial finding that children born to mothers on “any kind of antidepressant … had 50 percent higher risk for [autism]” could somehow morph into “no significant risk.”

“When they control for confounders like this,” Healy explained, “what happens is they reduce the size of the sample – and this reduction makes the increased risk no longer statistically significant.”

“But,” he warned, “it’s still an increased risk. By saying it’s not ‘statistically significant,’ these researchers are inviting you to agree there is no increase in risk – which is wrong.”

“Why are they inviting you to do this? I think because they are trying to hide the problem,” said the outspoken Healy.

Then I went back to Kaiser Permanente’s Lisa Croen, an expert on autism research and lead author of the first American study.

Noting that the Danish research “didn’t find an independent effect of SSRIs on autism risk once they controlled for maternal depression,” Croen told me:

However, only 20 percent of those women who took antidepressants had a diagnosis of depression, so analyses trying to tease apart the treatment from the indication for treatment may have been biased.

“Biased”? “Trying to hide the problem”? What’s going on here?

Adam Urato, M.D., assistant professor of maternal-fetal medicine at Tufts University School of Medicine in Boston, sizes up the Danish study this way:

In the Danish registry we do see an association between SSRI antidepressant use and child autism, but the authors state that the result is not statistically significant. What this means statistically is that the authors cannot say that an association exists with 95 percent certainty. But for most patients and the public, 95 percent certainty is not necessary to cause concern.

Indeed, even the Danish study’s lead researcher, Anders Hviid of the Statens Serum Institute in Copenhagen, agrees, in the words of a WebMD report, that “the findings do not prove that SSRIs carry no autism risk. And a connection is biologically plausible, Hviid said.”

Nevertheless, our big media went utterly hog-wild with this story, their headlines triumphantly – if ignorantly – trumpeting the news:

Hooray! Except – that’s not what the research says.

‘Pretty well certain’

I asked Dr. Healy, author of the highly acclaimed 2013 book, “Pharmageddon,” for a reality check on the state of research on the antidepressant-autism link.

“That these drugs cause ASD is pretty well certain,” he confirmed in an email, adding: “At this stage, the science is looking increasingly solid. I think virtually every study looking at this issue so far shows increased rates of developmental delay in children born to mothers on SSRIs during the first trimester and through pregnancy. The biological mechanisms through which this is happening are also increasingly understood.”

The “biological mechanisms” Healy mentions are no doubt what head Danish researcher Hviid was referring to when acknowledging a connection between SSRIs and autism is “biologically plausible.”

It all has to do with brain’s main neurotransmitter – serotonin.

Basically, the “biological mechanism” consists of chemically interfering with the mother’s serotonin levels – exactly what SSRI antidepressants do – which in turn, researchers warn, has been proven to affect the in-utero offspring’s brain development. As the authors of one important animal study put it: “Repeated findings of elevated platelet serotonin levels in approximately one-third of children with autism has led some to believe that dysfunctional serotonin signaling may be a causal mechanism for the disorder.”

Indeed, for physicians knowledgeable on this issue, the relatively few human studies are just the most recent arrivals in an already large and compelling body of research. For years, animal studies have reached the same disturbing conclusion.

Writes Urato: “Study after study, after study, after study, after study, after study, after study, after study, after study (and these are only a few – there are many more) show changes in the brain and behavior that result when the serotonin system is altered during development by the use of the SSRI antidepressants. In the discussion section of these manuscripts, again and again, the authors warn us that their findings of harmful effects in animals should make us concerned with using them in humans.”

After all, Urato summarizes: “A developing embryo and fetus has millions of serotonin receptors, and serotonin plays a critical role in development. Why wouldn’t chemically interfering with this system affect human development – particularly in the brain? The SSRI antidepressants have been shown to be linked to miscarriage, preterm birth, and other pregnancy complications that suggest that the drugs can cause injury to the developing baby/pregnancy. It should come, then, as no surprise that such medications could injure the fetal brain.”

‘Drug salesmanship’

As it happens, there are dozens of other reasons for pregnant mothers to avoid antidepressants.

“Current research suggests that antidepressant use (typically the SSRIs) by pregnant women is associated with increased risks of miscarriage, birth defects, preterm birth, preterm premature rupture of membranes, preeclampsia, and decreased fetal growth,” says Urato, who adds:

After birth, newborns who were exposed to antidepressants in utero have increased rates of what is called the newborn behavioral syndrome, which can consist of a variety of symptoms including tremors, agitation, excessive crying, respiratory difficulties and seizures. Exposed newborns also have been shown to have changes in heart conduction (i.e., the prolonged QT syndrome) and a potentially fatal condition called Persistent Pulmonary Hypertension of the Newborn (PPHN) in which the arteries to the baby’s lungs are constricted leading to trouble breathing or, in severe cases, death.

And Time magazine reported that “new research, published in the Archives of General Psychiatry, finds that women who took antidepressants during pregnancy were more likely to have babies with reduced head size and had twice the risk of preterm birth, compared with depressed women who did not take medication.”

Despite all the profound negatives, are there cases when a pregnant mother should still take antidepressants?

Croen tells me, “Individual clinicians and their patients must evaluate the research results in the context of their specific situation and make decisions accordingly.”

Urato expands on this theme:

I frequently give lectures on this topic and am asked, “What about the woman with severe depression who is suicidal when she comes off her antidepressant?” To me, it sounds like she should stay on the medication. But, let’s be clear, the vast majority of women on these drugs have mild to moderate depression. Furthermore, my main point on this is not that we should be telling anyone what to do. Psychotropic medication use during pregnancy is a personal choice and these women need care and support. But what they also need is accurate, correct, and complete information so they can make an informed decision; that is not what is currently happening.

Regarding that “vast majority of women” who are mildly to moderately depressed, Psychology Today offers some dumbfounding facts:

  • More than two-thirds of those on antidepressants are not currently depressed.
  • Since the placebo response rate for mild depression approaches 50 percent, many people are using antidepressants as placebos – incurring their side effects and costs without any real benefit.
  • The sharp escalation of antidepressant use in those with mild or nonexistent disorder suggests that much of the prolonged use is unnecessary and placebo driven.
  • Most of the prescriptions are written by primary care doctors, with little training in psychiatric diagnosis and treatment, after very brief visits and under the influence of drug salesmanship.

In “Pharmageddon,” Healy has a lot to say about “turbo-charged pharmaceutical industry marketing”: “The horrors are best caught by the example of the increasing numbers of pregnant women who religiously steer clear of alcohol, tobacco, soft cheeses, or anything that might harm their unborn child, but who are nonetheless being urged by their doctors to take drugs like the antidepressants – now the most commonly prescribed drugs in pregnancy – even as the evidence accumulates that these drugs cause birth defects, double the rate of miscarriages, and cause mental handicap in children born to mothers who have been taking them.”

More than half a century ago, in what was probably history’s worst pharmaceutical disaster, the German drug thalidomide was widely marketed, over the counter, to pregnant women to help them sleep better, and to cope with nausea and morning sickness. It worked – thalidomide relaxed and relieved the uncomfortable symptoms of pregnant mothers. But it also caused thousands of babies to be born with malformed or missing limbs, as well as blindness, deafness, deformed eyes, hearts, alimentary and urinary tracts. Worldwide, out of 10,000 reported cases of afflicted infants, only half survived.

Like the sinking of the Titanic, the thalidomide disaster brought into being new regulations around the world, including in the U.S., designed to prevent a recurrence.

What a sad and ironic scenario, then, that more than 50 years later, we are enticing millions of pregnant mothers to take powerful and poorly understood drugs to remedy a supposed brain problem – a problem experts admit could in most cases be managed without antidepressants – and we end up creating a real brain problem for their children.

Yet too many doctors remain “addicted” to drugs as a quick, one-size-fits-all solution to the anxieties, fears and conflicts of the troubled souls looking to them for understanding and help. Likewise, most “mainstream” journalists, seemingly oblivious to reality, just keep on urging expectant mothers to ignore all that nasty research and “stay on their meds.”

Meanwhile, for those who remain unconvinced by years of researchers’ warnings and who require even more conclusive evidence of the antidepressant-autism link, Croen tells me her Kaiser Permanente team is engaged in a major new study “conducted in six distinct geographic locations across the U.S.” and funded by the CDC. She anticipates the results will be released publicly sometime during 2015.

Read David Kupelian’s previous articles in this series:

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