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Investigating Outcomes Following the Use of Selective Serotonin Reuptake Inhibitors for Treating Depression in Pregnancy

A Focus on Methodological Issues

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Abstract

The aim of this review was to critically appraise the existing literature with a particular focus on identifying methodological issues associated with studying outcomes following the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy.

Existing studies evaluating outcomes following prenatal SSRI exposure suffer from a number of important methodological limitations that should be taken into account when interpreting their results. The contradictory results obtained from prospective and retrospective cohort studies and case-control studies could be accounted for by dissimilarity between study populations, selection bias, detection bias, confounding, or differences in underlying maternal illness, data sources used, exposure classification, follow-up and statistical power/analysis. Only a small number of studies actually account for underlying maternal illness and how this may lead to adverse pregnancy outcomes. Even when such information is available, studies that include data on maternal illness have small sample sizes, limiting the statistical power to identify statistically and clinically relevant associations. Pregnancy outcomes may be confounded by the higher incidence of smoking, alcohol consumption and substance abuse frequently encountered amongst those suffering from depression, factors that are often insufficiently controlled for.

While evidence of associations between prenatal SSRI exposure and adverse pregnancy outcomes are conflicting, there is an urgent need to evaluate how the particular SSRI used, the dose, timing and duration of use, genetics (maternal, paternal and/or fetal), concomitant medication use, maternal characteristics and underlying maternal illness all interact to alter pregnancy outcomes.

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Acknowledgements

Janna L. Morrison was supported by a Career Development Award from the National Heart Foundation of Australia and the National Health and Medical Research Council, and a South Australian Cardiovascular Research Network Fellowship (CR10A4988). Luke E. Grzeskowiak and Andrew L. Gilbert have no conflicts of interest to declare that are directly relevant to the content of this review.

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  1. Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia

    Luke E. Grzeskowiak & Andrew L. Gilbert

  2. Early Origins of Adult Health Research Group, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia

    Janna L. Morrison

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  1. Luke E. Grzeskowiak
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Correspondence to Luke E. Grzeskowiak.

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Grzeskowiak, L.E., Gilbert, A.L. & Morrison, J.L. Investigating Outcomes Following the Use of Selective Serotonin Reuptake Inhibitors for Treating Depression in Pregnancy. Drug-Safety 34, 1027–1048 (2011). https://doi.org/10.2165/11593130-000000000-00000

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