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

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.