Monday, October 5, 2009

Pregnancy & Depressive Relapse

I was looking at an article in JAMA from 2006, which was about pregnant women taking antidepressants. They were followed through pregnancy, and depressive relapses were related to changes in antidepressant dose. Here's a link to the abstract:

The study is too weakly designed to allow strong conclusions. Yet the abstract makes a statement about "pregnancy not being protective" which--while possibly true--is not directly related to the findings from the study. This criticism was wisely conceived by the author of "The Last Psychiatrist" blog:

Yet the JAMA study is not uninformative.

And the criticism mentioned above goes a bit too far, in my opinion. The critique itself makes overly strong statements in its own title & abstract.

It appears quite clear that pregnant women with a history of depressive illness, who are taking antidepressants, but decrease or discontinue their medication during the pregnancy, have a substantially higher risk of depressive relapse.

Because the study was not randomized, we cannot know for sure that this association is causal. But causation would be reasonably suggested. It does not seem likely that this large effect would have been caused by women whose "unstable" depressive symptoms led them to discontinue their antidepressants (i.e. it does not seem likely to me that "reverse causation" would be a prominent cause for this finding). I think this could happen in some cases, but not frequently. Nor does it seem likely to me that a woman already taking an antidepressant, who becomes more depressed during the pregnancy, would therefore stop taking her medication. This, too, could happen (I can think of clinical examples), but I don't think it would be common. It seems most likely to me that the causation is quite simple: stabilized depressive illness during pregnancy is likely to become less stable, and more prone to relapse, if antidepressant medication is discontinued.

The critique of this article also discusses the fact that women in the study who increased their doses of medication also had higher rates of depressive relapse, yet this fact is not mentioned very much in the abstract or conclusion. This finding is also not surprising--what other reason would a pregnant woman have to increase a dose of medication which she was already taking during her pregnancy, other than an escalation of symptoms? In this case, depressive relapse (which can happen despite medication treatment) is likely the cause of the increased dose--the increased dose is unlikely to have caused the depressive relapse.

Yet, as I said above, the study only allows us to infer these conclusions, as it was not randomized. And I agree that the authors overstate their conclusions in the abstract. In order to more definitively answer these questions, a randomized prospective study would need to be done.


Anonymous said...

New study suggests that mothers on anti depressants correlate positively with childhood ASD symptoms? The rate was very small so I am not really convinced due to all other confounds....


Do you know of any other strong evidence that antidepressants during pregnancy have an observable effect into the infants future childhood? (this is something I haven't really considered?)

GK said...

I don't know of good evidence one way or the other.
The closest type of information I think is out there is some data from animal studies. Here's an example:
This article certainly has a cautionary point of view, based on the evidence from rodent studies.
But once again, I think the risk to the fetus from maternal depression is high as well, and would need to be balanced with the relatively unknown risk of the medication.

A fair conclusion at this point would be to aim for thorough non-medication treatment of depression in pregnancy, and if medications are needed to keep the regimen simple with the lowest possible doses.