A systematic review and meta-analysis considering the SSRI, SNRI and TCA classes of antidepressants and the risk for congenital heart defects

Abstract

AbstractBackgroundAntidepressant use during the first trimester is reported in 4% to 8% of pregnancies. The use of some selective serotonin reuptake inhibitors (SSRI) during this stage of gestation has been identified as increasing the odds for congenital heart defects, however little is known about the safety of non-SSRI antidepressants.ObjectiveTo assess the odds of congenital heart defects associated with the use of any antidepressant during the first trimester of pregnancy. To investigate individual classes of antidepressants: SSRIs, serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and individual antidepressants.Data sourcesPubMed and Embase were searched without restrictions from inception till 2 January 2020.Study selectionProspective and retrospective cohort and case-control studies were included if they documented the maternal usage of antidepressants during the first trimester of pregnancy and assessed the presence of congenital heart defects.Data extraction and meta-analysisData were extracted by two independent reviewers and the endpoint assessed was congenital heart defects. Where studies reported multiple results for different types of heart defects or individual antidepressants, results were combined when possible. Analyses assessing individual antidepressants and classes of antidepressants (SSRIs, SNRIs and TCAs) were undertaken.ResultsA total of 16 studies were identified, encompassing 4,564,798 pregnancy outcomes. The odds ratio for maternal use of any antidepressant and the presence of congenital heart defects from the mixed-methods meta-analysis was 1.22 (95% confidence interval (CI): 1.11 to 1.33).Analyses of antidepressants by class produced an odds ratio of 1.50 (95% CI: 1.19 to 1.89) for maternal SNRI use during the first trimester of pregnancy and the formation of congenital heart defects. A significant odds ratio of 1.22 (95% CI: 1.12 to 1.33) was reported for SSRIs. For the TCA class, no increased odds ratio was found.Analyses of individual antidepressants produced significant odds ratios of 1.53 (95% CI: 1.25 to 1.88), 1.28 (95% CI: 1.01 to 1.62), 1.28 (95% CI: 1.14 to 1.45) and 1.23 (95% CI: 1.01 to 1.50) for paroxetine, fluoxetine, sertraline and bupropion respectively.ConclusionWhile some insight has been gained into which classes of antidepressant and individual antidepressants pose more risk than others for causing congenital heart defects, information regarding some antidepressants is still lacking.