Babies whose moms used antidepressants during pregnancy visit the doctor more often and have higher risks of certain health problems than other kids their age, according to a new study that examined medical records of nearly 39,000 Norwegian children through the first year of life,Reuters reports.
The study found rates of congenital heart defects and physical therapy, which is a potential sign of movement-related problems, were elevated among babies whose mothers used antidepressants throughout pregnancy. These children also tended to have more doctor visits and higher rates of such health problems as respiratory and digestive symptoms. However, those rates were also elevated among children whose mothers had stopped using antidepressants before pregnancy.
This raises the possibility that the risks were related to the mother's depression itself, rather than antidepressant use, according to researcher Tessa Ververs of the University Medical Center Utrecht in the Netherlands. But the question of whether to continue on antidepressants during pregnancy is not simple, Reuters writes.
Some recent reports have linked the meds to problems in newborns, including cases of congenital heart defects. Antidepressant use in the third trimester has also been connected to higher risks of respiratory distress, feeding problems and irritability in newborns, the researchers note in their report published in the British obstetrics journal BJOG. But there are also concerns about leaving depression untreated in expectant mothers, at a time when stress can be high, according to Reuters (here is the abstract).
Of the 38,602 babies in the current study, 197 were born to moms who used antidepressant throughout pregnancy. Another 820 stopped using the meds before pregnancy, while 543 used them only at certain points during pregnancy. Most women on medication during pregnancy, 71 percent, used a selective serotonin reuptake inhibitor (SSRI) such as Paxi or Prozac.
23 Comments
I wonder why they didn't identify mothers with depression who weren't taking medication for it. Seems that would be a logical comparison group.
Harpy, They probably just left that little tidbit out. It is ludicrous for one to believe that taking antidepressants during pregnancy isnt harmful to the fetus/baby. Bottom line, whatever mommy ingests, so does baby. Alcohol is a perfect example,..yes?
I agree that whatever mommy injests baby injests; however, if depression is a physiological condition, it would be reasonable to expect the study to identify mothers with depression weren't taking medication for it. Depression affects chemistry in the body so what ramifications does that have on the baby.
Jackson Roe says.."Depression effects chemistry in the body".... Would you please provide the Pharmalot readers with the scientific evidence to back up that statement. Eagerly awaiting your reply.
Jackson,
Even if depression did impact chemistry - or rather, if stress led to high cortisol - antidepressants do not lower cortisol but raise them. They raise serotonin leading to serotonin syndrome. Serotonin controls smooth muscle tissue constriction and altering levels of hormones artificially in the mother and baby has disastrous effects on the baby. The effects are well documented by the AMA and numerous others.
Here is a link to an article about how GSK knew since the early 1980s that Paxil caused birth defects but planned to bury the results:
http://tinyurl.com/yghf2lc
Here are a couple of links you might like to read on the AMA reports and FDA MedWatch reports.
http://tinyurl.com/yjo4psf
http://tinyurl.com/mj8ul2
Warnings/Studies Showing Risks Associated with Antidepressants and Pregnant Women or New Mothers:
There is ample evidence to support the risks associated with placing pregnant women or new mothers on antidepressant drugs:
* September 7, 2005: The Australian Therapeutic Goods Administration issued an information sheet to health professionals warning that SSRI antidepressant use—especially Paxil—in early pregnancy could cause congenital [defect at birth] heart abnormalities in newborns.[i] * September 27, 2005: The FDA and GlaxoSmithKline issued a warning that pregnant women taking Paxil or other antidepressants during their first trimester of pregnancy, placed their newborns at increased risk of major congenital and cardiovascular [heart] malformations at birth.[ii] * February 9, 2006: The New England Journal of Medicine found that mothers who took SSRI antidepressants in the second half of their pregnancies were 6 times more likely to give birth to infants with a lung disorder called persistent pulmonary hypertension (PPHN). The condition occurs when a newborn’s circulation system does not adapt to breathing outside the womb and causes high pressure in the blood vessels of the lungs making them unable to get enough oxygen into their bloodstream and can be fatal. Between 10% and 20% of infants with PPHN would die even if they receive treatment.[iii] * March 10, 2006: Based on the New England Journal of Medicine study, Health Canada issued a warning that SSRI antidepressants and other newer antidepressants when taken by pregnant women placed newborns at risk of developing the rare lung condition; persistent pulmonary hypertension or PPHN.[iv] * April 7, 2006: A Canadian study from the University of Ottawa published by the American Journal of Obstetrics and Gynecology, found pregnant women who used SSRI antidepressants were more likely to have premature and low birth weight babies.[v] * June 2006: An Archives of General Psychiatry study found women who take antidepressants during pregnancy at risk of giving birth to children with respiratory problems.[vi] * July 19, 2006: The FDA warned of the risk of a fatal lung condition in newborns whose mothers took SSRIs during pregnancy. The agency added it was seeking more information about persistent pulmonary hypertension in newborns from the drugs. It asked drug makers to list the potential risk on their drug labels.[vii] * November 2006: The journal Epidemiology published a study entitled “Maternal Use of Selective Serotonin Reuptake Inhibitors and Risk of Congenital Malformations.” Researchers did the study from Aarhus University. It found that pregnant women who take SSRI antidepressants are more likely to have babies with birth defects than mothers who don’t take these drugs.[viii] * August 2007: The American Journal of Psychiatry published a study that determined that antidepressant use during pregnancy was associated with premature births.[ix] * September 18, 2007: A study published in the Annals of Internal Medicine of nearly 500,000 women by researchers at the University of Pittsburgh Medical Center found that nearly 50% of women taking a prescription drug that could cause birth defects did not receive warnings to avoid pregnancy. * Moreover, experts say the seriousness of a life-threatening lung disorder found six times more often in infants born to mothers who take antidepressants during pregnancy is not being adequately conveyed to women while they are considering whether to use the drugs.[x] * The Physicians’ Desk Reference (PDR) states: “Like many other drugs, paroxetine [chemical name for the antidepressant Paxil] is secreted in human milk, and caution should be exercised when Paxil…is administered to a nursing woman.”
The point that stands out here is that heart birth defects were detected more in the continuous antidepressant users and not the other groups.
The abstract states:
"Children continuously exposed to antidepressants had an increased risk of cardiac interventions such as cardiovascular surgery or heart catheterisation, relative risk of 5.6 (95% CI: 1.8–17.4). The risk of physiotherapy was twice as high in the antidepressant group compared with the control group (relative risk 2.0; 95% CI: 1.5–2.6)."
The authors also talk about depressed women maybe being unable to deal with their babies health problems and I took it to mean that maybe they might run to the doctor more often.
But then I don't know why the women who stayed on antidepressants still went to the doctor more often if the drugs did what they were supposed to do in treating depression.
Which of course we know, they do very little, if anything, in only the most severely depressed people.
I'm sure women who stayed on antidepressants would need to go to the doctor way more for their child's health problems, which are often increased to deadly dangerous levels as a result of antidepressant exposure.
It seems funny to me that anyone would want moms to take their kids to the doctor less as a sign of mental progress. Aren't moms supposed to be protective and proactive with their kids' health? But then once you start taking meds during pregnancy I guess any other protectiveness could be moot.
Lisa,
To address your question, and on the most superficial of levels without providing any citation but my own academic knowledge, depression causes pain. Your body reacts to pain by releasing chemicals. Depression also causes issues that doctors refer to "irritable bowel syndrome", which is a professional way of saying "we have no idea what's up with your digestive system". They will even prescribe mood elevators to try ammending this as the toxins collecting in your body begin leetching into your bloodstream.
Yeah. Good stuff.
Father Bulgeotski
"My own academic knoweledge". You meant to say your perception, and subjectivity, and that you have no scientific evidence, correct?
Portraying yourself as a man of the cloth wasnt a good idea, medical professional would have been more appropriate, and of coarse you could have provided your real name for legitimacy purposes, yes?
Neah,... Bad Stuff
If you look at the reviews of the recently approved antipsychotic asenapine (Saphris - Merck) you will find evidence from animal studies of dose dependent deaths both pre- and postnatally in animal pups exposed in utero and when breast feed. There is also some evidence of problems in human children exposed prenatally.
(Around the same time as this review was being written and just before approval was expected the American College of Obstetrics and Gynecology came out with a white paper indicating there were no problems with administering these drugs during pregnancy.)
Similar toxicities can be found in the public reviews for Zyprexa (olanzapine), indicating that structurally similar compounds are causing similar toxicities and that there were concerns from at least the mid-1990's.
The reviews for Saphris indicate that cardiac toxicities and some deaths after long term use are consistent with a phen-fen like toxicity, pulmonary arterial hypertension (PAH). PAH in neonates is typically misdiagnosed as sudden infant death syndrome (SIDS). The death rate from SIDS as reported by the CDC began to increase in the 1980's with the introduction of SSRIs. Besides SIDs you also see interuterine growth retardation and poor placental development beginning around the border between the 2nd and 3rd trimester when growth begins to take off. The CDC also reports that some the most common causes of infant death are related to poor placental development and interuterine growth retardation.
It's interesting to note that the background package for the recent FDA advisory committee meeting on the use of Zyprexa in children had several cases of SIDS listed in children of mothers who took Zyprexa. Also that there were documented cases of PAH with Geodon. Since adverse effects are typically not reported it's noteworthy that there are reports to the FDA of a toxicity that are consistent with preapproval animal and human studies. Especially as the number of cases of idiopathic pediatric PAH in the FDA database would require that every such case in the US would have had to be reported to the FDA.
I think it's also interesting that one of the things that's increased in this study is cardiac cathetarization. The question I have is why was the cathetarization done in the first place. Especially since this is how PAH is diagnosed.
I have found public information that documents that certain companies knew their antidepressants caused neonatal PAH at least as far back as 2001. Yet this was not reported in the medical literature until 2005 with FDA not issuing a statement until several months later in July 2005.
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109352.htm#persistent
Salmon
Thanks for the input, Salmon, it was very much appreciated. Back in my childbearing years, OBs' were hesitant to give a pregnant woman an aspirin, antibiotics or cold medicine. Times sure have changed..
Lisa,
One of my fears is that the recent push by companies for the combined use of SSRI's and atypical antipsychotic will cause the incidence of these toxicities to increase exponentially. Similar to what occured with Phen-Fen (one of which was an SSRI).
Besides neonates I fear that there may be increased risk in the elderly due to physiologic changes that occur with aging that make them more susceptable.
These cardiac toxicities may be part of the reason for the progressive shortening of life expectancy in adult schizophrenics taking antipsychotics since the 1990's (it used to be about 10 years less than non-schizophrenics and is now 25 years less).
I am also afraid of the combined use of atypicals and stimulants in children. According to the astra-zenenca studies in children 50% of study participants were on both classes of drug and this was associated with increased heart rate and blood pressure (which we know long term increases mortality). This will also be compounded by the overdosing that occurs in children as compared to adults.
FDA is clearly aware of these concerns as one reviewer wrote an article a few months before this AC meeting discussing the possibility with long term use (Drugs - Dec 2008), and as Tom Laughren the Psych division director alluded to it at the AC meeting. Yet if you look at the Pediatric written requests from from the psych group they consistently only require short (3 week studies) and indicate the toxicities should be "qualitatively" similar to adults.
These risks need to be considered in the context of benefit and when I do this I am even more concerned. It's not that I believe that psychoactive drugs are without benefit. In fact in some people the responses can be dramatic. Yet we need to be especially careful of these examples when they're held out to us as a dramatic response in a few people can drive the statistical differences in the average degree of response that we know overall is marginal overall. In addition antipsychotics:
1) have not been demonstrated to have benefit in the elderly in dementia
2) Addition of an antipsychotic to an antidepressant only increases efficacy rates by 10% (so if 20% response above placebo you now have 22%).
3) In Bipolar I disorder only 20% respond even initially and then based on FDA data it's only the most sickest patients and not the patients with BP-1 who are less sick and definitely not patients with BP-2 or BP-NOS. (they're not approved for this as every company knows that any study would fail so they simply aren't done.)
4) The usage of antpsychotics in 1% of all children 6 - 17 yo is clearly inappropriate.
Only 0.1% of schizophrenics have psychosis at < 18 yo and the incidence of BP-1 maxs out at 1% at 25 yo. (only half of whom are even eligible for an antipsychotic). 0.3% of all adults with BP-1 have an onset of symptoms between 13 - 18 yo yet it takes 8 years on average between onset of symptoms (e.g. mild depression or other symptoms and full blown mania) So overall the max usage of these drugs should be in the 10ths of a % between 13 - 18 yo and virtually nonexistant at younger ages. Especially since it's thought that most people are not diagnosed even if symptoms are present. Consequently the only conclusion that can be drawn is that the vast majority of pediatric use is inappropriate and likely malpractice.
Consequently when I look at the risks of atyical antipsychotics (and lets not forget suicide 1 in 200 and other toxicities such as agranulocytosis 1 in 1200 in with some atypicals, and death 1 in 80 otherwise healthy adults) compared to the marginal degree of efficacy in most people and the massive inappropriate use. I become very concerned.
Remember, 'Doctors bury their mistakes'.
Salmon
Harpy, that's an excellent question - I was thinking the same thing myself. I briefly looked over the article and it appears to be a retrospective study. From my understanding if someone presents at his/her doctor's office with chronic depression, the MD will usually recommend medication. Therefore finding (retrospectively) a group of patients with untreated chronic depression is likely to be difficult or impossible.
This raises the possibility that the risks were related to the mother's depression itself, rather than antidepressant use, according to the researchers."
It was this quote from the Reuters article that brought it to mind, Nathan. I don't like the idea of blaming the person over the medication, especially when "depressed women not on medication" wasn't a category. And the "mothers who'd stopped using" isn't good enough for me unless they prove there were no residual effects from the meds. How long before they got pregnant did they stop using? A week? month? year?
Also I would have to question how many of the women were actually diagnosed as clinically depressed since off-label prescribing is so rampant for these drugs. Granted, this particular study only required the women be on the drugs, but if they're going to extrapolate the information it's negligent to assume that's why they were all taking the medication.
And to your last point - I'd like to believe there are still people out there who've chosen to deal with their depression through diet, exercise and *therapy* rather than taking a pill.
Harpy writes: "I don’t like the idea of blaming the person over the medication"
They are blaming the disease, not the person. Big difference.
Huge gray area all around.
As always things are more complex than we can discuss briefly here.
The quote above does not discuss whether the mothers had gone back on drugs and were breast feeding. Even if this is not the case assuming that SSRIs work via raising serotonin and this increase in serotonin causes PAH via receptors unrelated to receptors responsible for alleviating depression, isn't it possible that normal increases in serotonin in response to depression may also cause similar cardiac toxicities but at a lower level.
Thus we shouldn't discount the importance of additional risks due to drug induced toxicities simply because there may be an elevated but lessor risk without drugs.
Other things we need to consider include absolute risks and the total incidence in a population like the US where there are 5 million births per year.
The incidence of deaths due to SIDS has gone from 9 in 1000 births prior to the introduction of SSRIs to 35 in 1000 births today. With 5 million births per year in the US we now have ~130,000 excess infant deaths PER YEAR in the US due to SIDS alone. (This of course doesn't include deaths due to other causes but with similar underlying mechanims which doubles the incidence). Consequently I have wonder how many deaths have occurred over the years that are due to SSRIs or antipsychotics over and above any due to the underlying disease.
Salmon
Correction the rates should have been per 100,000.
So total numbers would be 13,000 instead of 130,000 for just SIDS alone. Still over 25 years they add up and are several fold more than the deaths due to Vioxx and COX-2 inhibitors, and as with COX-2 the deaths do not include the much greater numbers of injured but not killed.
Salmon
"How long before they got pregnant did they stop using? A week? month? year?"
This is a critical piece of information that is lacking. We know that withdrawal can last MUCH longer than the advertised "few weeks", which would make an assumption that the drugs physiological effect is long lasting. Using that rationale that effect could still be acting on the fetus long after stopping the drug. Not having a control group of "never medicated Mom's" and their fetal cardiac outcomes makes the situation incomplete research at best.
Then there's the "did the depression cause the IBS, or did the IBS cause the depression" argument, which is still ongoing. We could also throw in the "did the depression medication cause the IBS?" Depression also causes issues that doctors refer to “irritable bowel syndrome”, which is a professional way of saying “we have no idea what’s up with your digestive system”
So by your statement if medicine can't figure out the cause they assign a mental health diagnosis? Do they tell their patients that they are being treated with a random drug for a situation with an unknown cause?
Again,.. Ms Laurie hits paydirt..
Salmon,
Another condition that is rarely discussed in regards to ssri's and antipsychotics, is neuroleptic malignant syndrome, a potentially painful death. IBS cant begin to compare to that of NMS
Lisa,
Good point. We also can't forget rhadomyolysis.
Yes there are a number of toxicities with both classes of drugs (and others) that may be synergistic. Other ones might include suicide, violence, and akathesia and hepatotoxicity with selected agents such as Zyprexa and Cymbalta. As opposed to the hepatotoxicity many of these toxicities may involve the serotonergic systems or the intracellular systems they effect.
Things like akathesia, lactation and gynecomastia, and to a lessor extent tardive dyskinesia are less serious in my eyes as they don't result in death.
Now do you think the additional studies of antipsychotics with antidepressants for depression were powered or sufficiently long to pick up on synergistic toxicities?
Salmon
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