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?