The only way to have missed hearing about this study would be to have no contact with the media in the last 24 hours. Right now, Matt Lauer is in the other room waxing eloquent and it was the top story on my news and medical alerts this morning. Last night, the experts on the news pointed out that it was a small though significant difference and the OB types talked about the dangers of untreated depression in pregnancy:
Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Childrenby Takoua Boukhris, Odile Sheehy, Laurent Mottron, and Anick BérardJAMA Pediatrics. 2015/. Published online December 14, 2015.
IMPORTANCE The association between the use of antidepressants during gestation and the risk of autism spectrum disorder [ASD] in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression.OBJECTIVE To examine the risk of ASD in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression.DESIGN, SETTING, AND PARTICIPANTS We conducted a register-based study of an ongoing population-based cohort, the Québec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Québec from January 1, 1998, to December 31, 2009. A total of 145 456 singleton full-term infants born alive and whose mothers were covered by the Régie de l’assurance maladie du Québec drug plan for at least 12 months before and during pregnancy were included. Data analysis was conducted from October 1, 2014, to June 30, 2015.EXPOSURES Antidepressant exposure during pregnancy was defined according to trimester and specific antidepressant classes.MAIN OUTCOMES AND MEASURES Children with ASD were defined as those with at least 1 diagnosis of ASD between date of birth and last date of follow-up. Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios with 95%CIs.RESULTS During 904 035.50 person-years of follow-up, 1054 children [0.7%] were diagnosed with ASD; boys with ASD outnumbered girls by a ratio of about 4:1. The mean [SD] age of children at the end of follow-up was 6.24 [3.19] years. Adjusting for potential confounders, use of antidepressants during the second and/or third trimester was associated with the risk of ASD [31 exposed infants; adjusted hazard ratio, 1.87; 95%CI, 1.15-3.04]. Use of selective serotonin reuptake inhibitors during the second and/or third trimester was significantly associated with an increased risk of ASD [22 exposed infants; adjusted hazard ratio, 2.17; 95%CI, 1.20-3.93]. The risk was persistent even after taking into account maternal history of depression [29 exposed infants; adjusted hazard ratio, 1.75; 95%CI, 1.03-2.97].CONCLUSIONS AND RELEVANCE Use of antidepressants, specifically selective serotonin reuptake inhibitors, during the second and/or third trimester increases the risk of ASD in children, even after considering maternal depression. Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy.
[Note: I added the bottom line – the % of their pregnancy cohort on ADs]
I generally stay away from the big population studies, mostly because I don’t have anything to say. But his one brought back some memories. I had left the Emory full time faculty, but I heard about their doings a lot, and the use of antidepressants in pregnancy was a hot topic. It seemed like Dr. Charlie Nemeroff and Dr. Zach Stowe were everywhere talking about the dangers of untreated depression and Dr. Stowe was particularly vocal about treating depression in pregnancy. I knew a number of OBs at the time, and they all talked about how helpful he was – I think mainly because he implicitly gave them permission to use ADs [that was in a time when the promotion of antidepressants was everywhere, and patients really did show up saying, "I’ve been told I have a chemical Imbalance"]. I saw a number of depressed, pregnant women in those days [the ones who were afraid to take medications], and I can attest to the fact that depressed and pregnant is a tough place to be. Some got better and some just endured. But I thought a lot about the use of SSRIs in pregnancy. Reading was no help. Everybody had strong opinions, but they seemed morally driven rather than scientific [from both sides]. I knew I was in the nay camp myself from the start, and I remember what I said back then when asked:
"The most amazing undergraduate course I ever took was Embryology. We spent hours and hours looking at slides of chicken embryos, and the changes from week to week were astounding. We know next to nothing about the what drives and directs such a remarkable transformation. I was taking that course shortly after the Thalidomide tragedies, and I could see how whatever forces were operating might be easily interrupted by any number of things – including drugs. I’m on the side of staying away from drugs during pregnancy not because of what I know, but because of what we collectively don’t know."
The reason I calculated the % of patients on ADs from their data was that it looked low to me [average 1.29%]. I think the general population on ADs is definitely higher than that [though I don’t really know about Quebec from 1998 to 2009]. And that’s compatible with what I’ve heard from many pregnant women – a feeling similar to mine. So perhaps the mothers-to-be vote is often nay as well.
We worry a lot about drugs being promoted for commercial reasons. I even implied that earlier talking about Drs. Nemeroff and Stowe. But there’s another force that’s more benevolent to consider – therapeutic zeal. The OBs that I knew back then weren’t in that entrepreneurial camp at all. They were solid citizens who were genuinely worried about their patients’ plight. And I expect that the doctors and pharmacists in Germany [where Thalidomide became OTC] were using it benevolently. Hyperemesis Gravidarum can be an absolutely miserable and sometimes dangerous symptom of pregnancy, and I would bet Thalidomide was hailed as a real breakthrough [until its dreadful outcomes became apparent].
I’m aware that in this instance, I’ve gone for do no harm over therapeutic zeal, but that anything I say to explain that is post-hoc. My choice is really rooted in my reaction to those slides from 50+ years ago. It feels to me like we don’t know enough about the process of embryonic development to do anything that might mess with it and that feeling doesn’t ever change. I wonder sometimes how much these kind of personal experiences determine how we look at science, make decisions about practice, etc. And as for Autism and AD use in pregnancy, the most we can say right now is that it’s not a negative study, and the usual – awaits further study, and replication needed…
Looks like they did not look at an important confounding variable – paternal age.
Interesting academic/industry collaboration
http://switchrx.ca
It is difficult to imagine a study in this area which will change minds on either side.
http://www.autismpolicyblog.com/2015/12/antidepressants.html
And… plus ca change.
http://blogs.scientificamerican.com/mind-guest-blog/rethinking-how-we-diagnose-psychosis/
The editorial in JAMA Pediatrics accompanying this report gets to the issue of absolute risk, from which Number Needed to Harm (NNH) can be derived. “In real numbers, the findings suggest that, compared with the population who stopped taking ADs in the first trimester, there may have been an additional 12 children with ASD than otherwise would have been expected out of the 2532 children exposed in utero during the second or third trimester.”
From that it looks like the rate of drug attributable cases of ASD in those children would be 0.47% (12 of 2352) and the resulting NNH would be 212 (100 divided by 0.47). For comparison, the Number Needed to Treat (NNT) to prevent the hard outcome of suicide in depression has been estimated at 560 in adolescents (an age group proxy for pregnant women). Whenever NNH is less than NNT, then caution indeed is in order, as Dr. Mickey states. On the other hand, treating depressed pregnant women may result in other benefits such as reducing suicide attempts or promoting postpartum confidence and success in parenting. We just don’t have all the answers.
Mickey,
Have you seen the columns by Adam Urato, on the MIA site?
http://www.madinamerica.com/author/aurato/
Perhaps I am missing something but it doesn’t seem like more research is needed to indicate that SSRIs and pregnancy don’t go together.
This article in particular seems to do a good job in thoroughly discussing the relevant issues such as a great increase in hard to the baby which could be kind of depressing.
https://www.madinamerica.com/2015/06/chemicals-have-consequences-antidepressants-pregnancy-and-the-new-york-times/
And be sure to read this section:
2. No one Wants a Pregnant Woman to Kill herself. (Anecdotes have Limitations)
AA,
Adam’s article is good. It may not need confirmation from your point of view, or Adam’s, or even mine. But if you saw the news interviews, there are a lot of OBs that need convincing and the gold standard is replication. I’m glad Adam mentioned his cases and how sick some of them get. The treatment of depression in pregnancy is a whole topic unto itself with many dimensions. These patients have a hard road to travel with or without medications…
“Treating depressed pregnant women” need not demand psychiatric drugs.
As social isolation is a key factor in both “depression” and “post-natal depression,” simply promoting peer support groups for pregnant women, where women can make friends in their geographical areas, might be a compassionate, cost-effective way to improve quality of life all around.
Its just incredible the lack of common sense with an issue regarding medicating women in pregnancy.
There’s only two questions you ask a psychiatrist who’s more than willing to offer medications to a woman who is pregnant, especially in the first trimester:
The first is, “would you as a female provider or your wife if a male providet take medications while pregnant”, and the second is ” would you be supportive of giving meds to a family member or someone close to you while pregnant?”
It is just amazing to watch the provider then either squirm and babble incoherently, or just reflexively say yes and then try to change the topic literally in the next sentence
Which speaks volumes about who you’re dealing with when they’re so willing to medicate a woman in pregnancy!
Did they separate out women who took antideps during lactation? The only way to isolate the independent variable is to not include women who took during pregnancy and elected for bottle feed or go off antideps postterm. Or you could have a third group who took during lactation but not pregnancy. Obviously the term of pregnancy matters too as third term is clearly much lower risk of problems.
Also the problem with ASD is the same with MDD…it’s so broadly defined that construct validity is question. If you used the old definitions, it would be a better design.
I’ve gotten to the point with psych research that I have to question everything because of the definitions they are using. In the best hands with the most brilliant and ethical researchers because they are hamstrung.
You’re right, James. The framers of DSM-III through DSM5 tried to finesse the issue of diagnostic validity and they led the field into a quagmire. See here.
That link doesn’t work right. Here is another.
I worked under Dr Mottron and can dig out the situation of SSRIs in Quebec. Anyone interested?
Al