Paroxetine and congenital malformations: Meta-Analysis and consideration of potential confounding factors

Antidepressant Exposure During Pregnancy and Congenital Malformations: Is There an Association?

“…Note, however, that this was not a consistent finding, as our main analysis, which was with the higher quality studies, was not significant, although it was reduced to 4 studies. Several meta-analyses previously did report an increased risk for cardiovascular malformations with paroxetine (ie, Bar-Oz et al, 13 Wurst et al 16 ) but, unlike Wurst et al, 16 we did not find an increased risk for congenital malformations with this drug. Ours is the first meta-analysis, to our knowledge, to specifically examine the type of malformation implicated, and our results suggest that septal heart defects are associated with antidepressant exposure.…”

“…Furthermore, many more women with depression may request diagnostic testing of their infants compared to healthy mothers. 13 All of the aforementioned potential sources of bias could increase the chance of false detection of an increased risk for septal defects and SSRI exposure. More research is certainly needed that focuses on these types of malformations, with the goal of determining whether an association with the type of cardiovascular effect exists, if it is dependent on a particular drug, or if indeed it is a class effect.…”

“…Sources of uncontrolled bias leading to the marginal increased risk for septal defects may include detection bias. 13 Women with depression may be more likely to have an ultrasound and echocardiogram in pregnancy and after birth. They may also have an increased use of health care services due to the depression itself or due to the publicity surrounding the risks of congenital malformations with SSRIs.…”

“…63 Previous research suggested that the inclusion of common reversible Grigoriadis et al heart defects such as the ventral ones may inflate any existing association found with antidepressant exposure. 13,49,52,63 We attempted to differentiate between atrial septal defects and ventral septal defects, but there were not enough studies. Although our ventral septal defects analysis was not significant, the RRs were in a similar range to the overall septal defects analysis, which was significant.…”

“…3,7 The results of prior meta-analyses have been conflicting. Several have found no evidence of increased risk of major congenital malformations above the baseline [8][9][10] rate, which has been widely cited as 1%-3% for any pregnancy in North America [11][12][13][14] and less than 4% for minor congenital malformations. 15 The most recent meta-analyses did report an increased risk for congenital malformations 16 and cardiac malformations 13,16 with paroxetine exposure specifically.…”