Is too much caution enough?

Comments on an article by N. Myles et al. (see record [rid]2013-39402-008[/rid]). Myles et al. provide us with a systematic review of first-trimester fetal exposure to SSRIs and the risk of congenital malformations. This review, like several others, identified a small, but significantly increased risk for congenital malformations associated with SSRIs (odds ratio: 1.10), with two agents, fluoxetine and paroxetine contributing to this risk. It is important to emphasize that while this is a statistically increased risk, the absolute risk of congenital malformation associated with SSRIs remains very low. Studies on congenital abnormalities associated with first-trimester exposure to SSRIs have produced inconsistent results, with some studies reporting an increased risk, whereas others have not, depending on the type of study and the sample size. The most consistent finding relates to the risks associated with exposure to paroxetine. An obvious conclusion from this paper, and from the other meta-analyses, is that the SSRIs are safe to use in pregnancy. After all, the major concern about fetal exposure to drugs is the risk of congenital malformation. The first issue relates to SSRIs having other effects on the developing fetus and the course of pregnancy that need to be considered. Second, it has recently been reported that infants who have been exposed to SSRIs during pregnancy, have an increased risk of having a low Apgar score at 5 minutes; this is a risk factor for poor intellectual performance in adolescence. Finally, SSRIs themselves can have an effect on the course of the pregnancy, with one study finding an increased risk of gestational hypertension and pre-eclampsia among women taking SSRIs during pregnancy. The second issue relates to the nature of depression in pregnancy—if indeed all the depressive-like symptoms seen in pregnancy are in fact due to a major depression. The final issue is the severity of the depression, as many women may be experiencing mild to moderate depression. There is increasing evidence about the low efficacy of SSRIs in mild to moderate depression, with little difference seen between drug and placebo in clinical trials. It needs to be emphasized that pregnant women are routinely excluded from clinical trials. Non-pharmacological treatments may be more appropriate for depression in pregnancy. There are two take-home messages. First, while there is a small, but acceptable increased risk of congenital abnormalities following exposure to SSRIs, there are other risks to be taken into account. Given this, I would argue that caution is still warranted in prescribing antidepressant medication during pregnancy, especially when there are alternative, effective and safe non-pharmacological treatments that can be applied for depression in pregnancy. If there are clear indications that pharmacotherapy is necessary (such as for moderate to severe depression or disabling anxiety), then it should be used ideally at the lowest effective dose. Second, we should always be mindful of the risks associated with antidepressants when prescribing them to any woman of childbearing age. Women should be informed about these risks at the initiation of treatment and their treatment reviewed if they want to conceive. If this is not under consideration, then having a discussion about contraception is important.