There’s Something About Mary

A paper looking at antidepressants and birth defects in Denmark has just appeared. Anyone can download it and read for themselves (Jimenez-Solem et al 2012). It’s worth reading.

The published data demonstrate an increased rate of major birth defects on SSRIs which fits what almost all other studies have found. But this study also finds that women who have stopped their SSRI 6-9 months previously are at a similarly increased risk.

This has led some of the authors apparently to say that the problem may stem from the underlying depression rather than its treatment. The paper puts it in a different way – there is something about the redemption of a prescription for an SSRI that leads to birth defects.

This is an extraordinarily worrying paper – perhaps one of the scariest in recent years.

The authors make the usual point about more research being needed. No paper is perfect and in this case there are known hazards with the method (prescription redemption records) the authors have used. Prescription redemption records fail to pick up many of the people taking a drug – and this might therefore explain why in this study relatively few Danish women register as being on antidepressants.

First the children born to women who are on or have been on an SSRI have a roughly doubled rate of heart defects even though many major heart defects will be terminated. The higher the dose of SSRI the woman is on, the higher the risk of a heart defect in her baby.

The risk of a neural tube defect is no higher – but almost all neural tube defects are terminated in Denmark. The rates of termination in other countries looked at are higher in women on SSRIs, so this is presumably also the case in Denmark.

In contrast, the children born to women on other antidepressants do not have this increased risk. This is a particularly interesting finding in the Danish study in that in the 1980s the Danish University Antidepressant Group (DUAG) ran studies demonstrating that tricyclic antidepressants (TCAs) work in severely depressed patients when SSRIs are ineffective. So it seems a reasonable assumption that the women in the TCA group in this study were more likely to be severely depressed than the women in the SSRI treated group but the women on TCAs do not have as high a risk of birth defects.

There is some risk of birth defects in the TCA group – not as high as in the SSRI group – but this most probably reflects the fact that some TCAs, like clomipramine and imipramine, are also serotonin reuptake inhibitors and some like desipramine and lofepramine are not. In the same way some antihistamines like diphenhydramine and chlorpheniramine inhibit serotonin reuptake and some don’t. Those that inhibit serotonin reuptake cause birth defects. Those that don’t inhibit serotonin reuptake don’t cause birth defects.

Crucially with antidepressants other than TCAs and SSRIs do not have an elevated risk of birth defects.

So what’s going on in the women who have stopped antidepressants for a few months but still seem to be at high risk of birth defects?

One option was outlined in Herding Women. Maybe these women, worried about the effects of taking something that sounds as unnatural as an antidepressant, figured that they’d switch to something more natural like St John’s wort, unaware that this also comes with a high risk of birth defects and miscarriages. Or maybe they switched to an antihistamine.

But the much more worrying option is this. SSRIs have far more enduring effects on the reproductive system and its related endocrinology than they have on mood. They shrink ovaries and testes and it is this that gives rise to the loss of libido associated with their use, which can sometimes be permanent. They reduce sperm quantity and function. These drugs really do have the kind of effects on testes and sperm that masturbation was once thought to have. Masturbation never did this, SSRIs do.

Before and After SSRIs

 

 

 

 

 

 

Ironically there is a striking similarity between this image and the usual image in advertisements of what SSRIs supposedly do – except of course the direction is reversed. There is no more evidence that this is the true effect of SSRIs on brain serotonin than there ever was that masturbation had the effects on semen outlined in the slide above.

Before and After SSRIs

 

 

 

 

 

 

 

Given comparably powerful effects throughout the endocrine system, effects that are far more substantial and enduring than any effects that the kinds of anxiety or depression for which SSRIs are given have on the endocrine system, it is much more likely that it is some direct effect of the SSRI that is the source of these birth defects in women than leaving their anxiety untreated has caused the problem.

Before the SSRIs came on stream, women who were diagnosed as depressed had a far more serious condition than women treated with SSRIs have now. This condition was variously called melancholia or endogenous depression. This is a condition that does lead to endocrine disturbances – raised cortisol levels – but melancholia has not been linked to birth defects.

The hypothesis that there might be a link between the kind of anxiety or milder mood disorders for which women get SSRIs now – in which there is no abnormality of cortisol – to birth defects is close to unprovable. What woman isn’t anxious at some point during her pregnancy?

Creating a culture where women were told that being anxious might cause their unborn child to have a birth defect sounds suspiciously like taking us back to the Middle Ages when women were told that birth marks on the faces of their children were caused by the mother looking at a fire.

It is far more likely that the risk of birth defects in women who have stopped their SSRI is mediated through some enduring epigenetic change or effect on the endocrine system brought about by previous treatment than it is that these birth defects are caused by untreated nerves. If this is the case, it means we do not know how long women have to stop SSRIs and other serotonin reuptake inhibiting antidepressants before it is safe for them to conceive.

Few doctors inform women of child-bearing years of the risks of dependence on an SSRI.  Few inform women of the risks of birth defects on an SSRI.  What is the right thing to say in the light of the most recent evidence? What would the American Woman who haunts these posts have to say?

3 COMMENTS

  1. I am an American woman who interestingly enough also had a baby in Denmark. I am grateful that I was not on antidepressants at that time or before. I have since been on them a few times for depressive symptoms starting about 15 years later. I do not have a diagnosis of chronic depression, thank God.

    My daughter born in Denmark is now expecting a baby herself. All I can say is that I warned her to avoid any psychiatric medications, no matter what, during the pregnancy. She is in total agreement, and does not need antidepressants for the present…. although she has needed them and taken them in the past for short periods.

    My other daughter has chronic depression and has been on anti-depressant medication for years. She has had great difficulty with recurring suicidal ideation. I honestly don’t know which anti-depressant she is taking as she is 24 and a practicing RN…..I’m on a “need to know” basis and we agree that I don’t need to know. But I warned her about the capacity of SSRI’s to create the exact problem that she is having. She has considerable insight, but she is kinda stuck….when she tries to wean off or switch to a less damaging med, she becomes so seriously anxious and suicidal she becomes unable to work….and jeopardizes her health insurance (which she needs for things like broken legs, God forbid). Her first job out of nursing school forced her to take a long leave of absence and eventually asked her to resign (which she refused to do)–because she sought help with suicidal thoughts! Punished for doing “the right thing.”

    As a practicing health care professional I am acutely aware of the fact that no psychiatric drug is safe for anyone’s pregnancy. As a mother, I am anxious for my children that they not harm my future grandchildren–inadvertently, by working to cope with their own depression or history of depression. Fortunately my pregnant daughter’s docs are all on board with the need to avoid any unneeded medication.

    But my other daughter, who is currently in a valiant fight to cope with chronic depression, is of greater concern to me. She has been depressed off and on since childhood. She has been off and on antidepressants as well. God grant that she doesn’t get pregnant anytime soon and that she can eventually wean off these drugs, whichever ones she is on. But the reality is that this will not happen overnight and she will require extensive support in the years to come, both vocationally and personally. It is hard to say whether or not she has a realistic chance of having children under these circumstances. She would never intentionally conceive if she could not go off of anti-depressants as she is very aware of the birth defect risk.

    For her, depression is life-threatening. When it is at its worst she has to fight off suicide like an invading assailant. When it is at its least, she has to fight to get out of bed and function to work and support herself. This is no passing malaise.

    My grandmother committed suicide in her late 30’s. My mother and her brother were 7 and 4 years old. Depression has left a horrible mark on my family and I myself work everyday to maximize my own mental health because I always have the family history in the back of my mind. I am proud of my mother that she lived to be 86 years old, but I know that it was a struggle for her as well. I don’t know why my own life has been as charmed as it has, but somehow I have had it much easier…. and I do NOT owe it to taking antidepressants.

    Dr. Healy, you are so right! This paper implies that women with chronic depression are damned if they do and damned if they don’t when it comes to motherhood. If they try to be mothers without the medication the outcome will be terrible, simply from depression alone. If they try to be mothers while taking antidepressants they are at a high risk for all kinds of birth defects and that could be a terrible outcome. The solution? It would seem that a woman with chronic or recurring depression (according to the study) perhaps should not have children. Hmmm. Sounds like a study that might support the proponents of eugenics.

    My RN daughter is a stubborn and determined soul and she will work it out. I have faith in her. It’s not so easy for most women with depression. We have to do what we can to help.

    • I’ve found that the major problem in getting off these tosic drugs is not the actual getting off, which can be incredibly difficult and time consuming, it’s finding things that promote wellness and well being to put in place of the drugs once you get off of them. The Icarus Project and a young man by the name of Will Hall have produced a “harm reduction guide” for coming off these nasty things. It’s become one of the best things around in helping people to taper and then get completely off. But it does no good to get off them if you have nothing to put in their place. There are numerous things to choose from and lots of things that can be done. Your daughter could tailor a regimen for herself based on her own personality and preferences. And you really have to work at your regimen to keep moving forward. but it can be done! that’s the really good message; it can be accomplished. If your daughter is stubborn that will be a great help thorugh getting off. One problem that most people don’t realize is that you suffer withdrawal when you try to get off and this is what causes so many problems. The psychiatrists lie and say that they aren’t addictive but we all know differently. Some of the drugs that are a bunch of little balls in a gel capsule have to be tapered by removing only one of those tiny little balls at a time in the tapering. It’s very time consuming and the saying is that it takes you as long to get off the damned things as you’ve been on them due to the fact that you hae to taper so slowly.

  2. I am glad you are mentioning men in your article and the effect of SSRIs on sperm production. My son was forcibly fed Risperidone which disrupts not only dopamine but serotonin reuptake as well, and the effect on his sexual functions was devastating. Although he has been off all medication for 3 years, he is only returning to normal now-he hopes!Psychiatrists and GPs don’t care. I wish somebody would look more closely into the effects of atypical antipsychotics and SSRIs on men. May be they are partly to blame for birth defects

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