Question: In pregnant women with current major depression, what is the most effective and safest antidepressant for reducing depressive symptoms?


There is currently insufficient evidence to draw meaningful conclusions about the effectiveness and safety of antidepressant therapy in pregnant women with major depression.

Four systematic reviews, all with major methodological limitations, reported results indicating that antidepressant use during pregnancy may be associated with adverse outcomes, including congenital cardiovascular abnormalities in the newborn, spontaneous abortion, and major congenital abnormalities in the newborn. However, it should be noted that all of these results were derived from comparisons of pregnant women with depression who were exposed to antidepressant treatments and un-exposed pregnant women who were not depressed; this approach is fundamentally flawed in that it takes no account of the possible effects of depression itself.

Further research is required to adequately explore the risks and benefits associated with antidepressant use in pregnancy. If randomised controlled trials are not considered appropriate a large, prospective cohort study of pregnant women with depression, including both women who are exposed to pharmacological antidepressant therapy during pregnancy and women who are not exposed, could be used as the basis for regression modelling. It is important that all study participants should have a diagnosis of depression and that other potential confounding factors are adequately considered. Meta-analytic techniques could be used if individual patient data (IPD) were available from existing studies. Standard meta-analysis, as used by the studies included in this summary, is not appropriate since each individual study is likely to adjust for a different set of confounding factors. Hence combining the results of these studies in a single model does not produce a meaningful effect estimate. 

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