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A Systematic Review and Meta-Analysis Considering the Risk for Congenital Heart Defects of Antidepressant Classes and Individual Antidepressants

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Abstract

Introduction

Antidepressant use during the first trimester is reported in 4–8% of pregnancies. The use of some selective serotonin reuptake inhibitors during the first trimester has been identified as increasing the odds for congenital heart defects; however, little is known about the safety of non-selective serotonin reuptake inhibitor antidepressants.

Objective

The objective of this study was to assess the odds of congenital heart defects associated with the use of antidepressants during the first trimester of pregnancy, and to update the literature as newer studies have been published since the latest systematic literature review and meta-analysis.

Methods

PubMed and Embase were searched till 3 June, 2020. Study quality was assessed, and study details were extracted. Meta-analyses were performed using RevMan 5.4, which assessed: (1) any antidepressant usage; (2) classes of antidepressants; and (3) individual antidepressants.

Results

Twenty studies were identified, encompassing 5,337,223 pregnancies. The odds ratio for maternal use of any antidepressant during the first trimester of pregnancy and the presence of congenital heart defects from the random effects meta-analysis was 1.28 (95% confidence interval [CI] 1.17–1.41). Significant odds ratios of 1.69 (95% CI 1.37–2.10) and 1.25 (95% CI 1.15–1.37) were reported for serotonin norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors, respectively. A non-statistically significant odds ratio of 1.02 (95% CI 0.82–1.25) was reported for the tricyclic antidepressants. Analyses of individual SSRIs produced significant odds ratios of 1.57 (95% CI 1.25–1.97), 1.36 (95% CI 1.08–1.72), and 1.29 (95% CI 1.14–1.45) for paroxetine, fluoxetine, and sertraline, respectively. The norepinephrine-dopamine-reuptake inhibitor bupropion also produced a significant odds ratio of 1.23 (95% CI 1.01–1.49).

Conclusions

The selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor classes of antidepressants pose a greater risk for causing congenital heart defects than the tricyclic antidepressants. However, this risk for individual antidepressants within each class varies, and information regarding some antidepressants is still lacking.

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Authors and Affiliations

  1. Clinical and Health Sciences, University of South Australia, North Terrace adjacent Morphett St Bridge, Adelaide, 5000, SA, Australia

    Courtney De Vries, Matthew J. Sykes & Michael Ward

  2. Quality Use of Medicines and Pharmacy Research Centre, University of South Australia, Adelaide, SA, Australia

    Svetla Gadzhanova, Michael Ward & Elizabeth Roughead

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  1. Courtney De Vries
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Correspondence to Courtney De Vries.

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No funding was received for this work.

Conflicts of interest/competing interests

Courtney De Vries, Svetla Gadzhanova, Matthew J. Sykes, Michael Ward, and Elizabeth Roughead have no conflicts of interest that are directly relevant to the content of this article and declare no support from any organization for the submitted work.

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CDV has the right to grant on behalf of all authors and does grant on behalf of all authors, a worldwide licence to the publishers and its licensees in perpetuity, in all forms, formats, and media.

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Authors’ contributions

ER and CDV designed the study. CDV performed the literature search. CDV and SG extracted data from the identified articles. CDV conducted the meta-analyses and drafted the manuscript. All authors reviewed the manuscript, contributed to its revision, and approved the final version submitted.

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De Vries, C., Gadzhanova, S., Sykes, M.J. et al. A Systematic Review and Meta-Analysis Considering the Risk for Congenital Heart Defects of Antidepressant Classes and Individual Antidepressants. Drug Saf 44, 291–312 (2021). https://doi.org/10.1007/s40264-020-01027-x

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