Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations

Abstract

Fluoxetine and paroxetine should be avoided in the first trimester and among those at risk of an unplanned pregnancy.

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

“…A meta-analysis of first trimester exposure to several classes of antidepressant confirmed these observations . Additionally, a meta-analysis found an increased risk of major malformations with fluoxetine and paroxetine exposure specifically in the first trimester (Myles et al, 2013). Although studies continue to examine this endpoint, the data do not point to a significant Prenatal Antidepressant Exposure association of prenatal antidepressant exposure and a specific pattern of congenital malformations.…”

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: a European register-based study

“…Thereafter, starting with paroxetine [22], the SSRIs have come under scrutiny particularly in relation to congenital heart defects (CHD) [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Although not all studies have supported this association [38][39][40][41][42][43][44][45], meta-analyses have found positive overall evidence [46][47][48][49][50]. Some non-CHD congenital anomalies have also been linked to SSRI exposure in first trimester pregnancy [24,29,32,[34][35] although this literature is much smaller.…”

Pharmacotherapy of obsessive-compulsive disorder during pregnancy: a clinical approach

“…[22][23][24][25][26][27][28][29][30][31] However, paroxetine and most recently fluoxetine are two SSRIs for which increasing evidence shows negative effects on the fetus. A recent meta-analysis by Myles et al 27 indicated that paroxetine (odds ratio [OR] = 1.29, 95% confidence interval [95%CI] 1.11-1.49) and fluoxetine but not sertraline or citalopram were associated with a higher risk of major malformations. Conversely, Grigoriadis et al 28 have reported that paroxetine and fluoxetine were not significantly related to major congenital malformations.…”

“…32 Three meta-analyses in the literature have reported odds ratios between 1.12 (95%CI 0.98-1.28) and 1.25 (95%CI 1.03-1.51) for congenital defects associated with fetal exposure to fluoxetine. 27,28,32 Although there are conflicting reports published, a greater number of studies on the use of paroxetine describe deleterious effects such as increased risk of cardiac malformations. 24,[26][27][28]31,[33][34][35] This increased risk is also supported by two recent meta-analyses (reported OR = 1.43, 95%CI 1.08-1.88 and 1.44, 95%CI 1.12-1.86).…”

“…27,28,32 Although there are conflicting reports published, a greater number of studies on the use of paroxetine describe deleterious effects such as increased risk of cardiac malformations. 24,[26][27][28]31,[33][34][35] This increased risk is also supported by two recent meta-analyses (reported OR = 1.43, 95%CI 1.08-1.88 and 1.44, 95%CI 1.12-1.86). 27,28 The OR for the same defects in fluoxetine users was reported to be 1.17-1.60 by three meta-analyses.…”