Evaluation of the Risk of Congenital Cardiovascular Defects Associated With Use of Paroxetine During Pregnancy

Einarson, Adrienne; Pistelli, Alessandra; Desantis, Marco; Malm, Heli; Paulus, Wolfgang D.; Panchaud, Alice; Kennedy, Debra; Einarson, Thomas R.; Koren, Gideon

doi:10.1176/appi.ajp.2007.07060879

Cited by 161 publications

(68 citation statements)

References 22 publications

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“…4 In 2005, based on early results of two epidemiologic studies, the US Food and Drug Administration (FDA) warned healthcare professionals that early prenatal exposure to paroxetine may increase the risk of congenital cardiac malformations and reclassified it to pregnancy category D. 5 Most malformations in the early reports leading to the FDA warning were septal defects. Since then, several studies have evaluated the teratogenicity of SSRIs and other antidepressants [6][7][8][9][10][11][12][13][14][15][16][17][18][19] , but considerable controversy remains as to whether this is a "serious concern or much ado about little" as noted in an editorial published with two of the reports. 13,1420 Existing studies have reported different associations, often in the context of multiple comparisons.…”

Section: Conclusion-resultsmentioning

confidence: 99%

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Huybrechts

Palmsten

Avorn

et al. 2014

Obstetrical &Amp; Gynecological Survey

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Background-There is controversy regarding whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants in pregnancy is associated with increased risks for congenital cardiac defects. In particular, concerns exist about a possible association between paroxetine and right ventricular outflow tract obstruction (RVOTO), and between sertraline and ventricular septal defects (VSD).

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Section: Conclusion-resultsmentioning

confidence: 99%

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Huybrechts

Palmsten

Avorn

et al. 2014

Obstetrical &Amp; Gynecological Survey

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“…This finding led the US Food and Drug Administration to advise women to avoid paroxetine during pregnancy if possible and to change pregnancy labeling from a category C to D. Paroxetine is the only SSRI whose pregnancy category labeling has changed. However, a recent meta-analysis 23 that reviewed both previously published and unpublished data noted no association between paroxetine and cardiovascular defects.…”

Section: Discussionmentioning

confidence: 99%

Congenital Heart Disease Associated With Selective Serotonin Reuptake Inhibitor Use During Pregnancy

Wichman

Moore

Lang

et al. 2009

Mayo Clinic Proceedings

147

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OBJECTIVE:To determine the risk of congenital cardiac abnormalities associated with use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. PATIENTS AND METHODS:We conducted a retrospective review of the medical records of all pregnant women presenting at Mayo Clinic's site in Rochester, MN, from January 1, 1993, to July 15, 2005, and identified 25,214 deliveries. A total of 808 mothers were treated with SSRIs at some point during their pregnancy. We reviewed the medical records of the newborns exposed to SSRIs during pregnancy to analyze their outcomes, specifically for congenital heart disease and persistent pulmonary hypertension of the newborn. RESULTS:Of the study patients, 808 (3.2%) took an SSRI at some point during the antenatal period. Of the 25,214 deliveries, 208 newborns (0.8%) were diagnosed as having congenital heart disease. Of the 808 women exposed to SSRI during pregnancy, 3 (0.4%) had congenital heart disease compared with 205 (0.8%) of the 24,406 women not exposed to an SSRI (P=.23). Of the total number of deliveries, 16 newborns were diagnosed as having persistent pulmonary hypertension of the newborn, none of whom had exposure to SSRIs (P>.99). © 2009 Mayo Foundation for Medical Education and ResearchR ecent data indicate that approximately 10% to 15% of women will have depression at some point during pregnancy or the postpartum period. 1,2 Untreated depression during pregnancy may lead to poor outcomes, including low birth weight, preterm delivery, or lower Apgar scores; poor prenatal care; failure to recognize or report signs of labor; and an increased risk of fetal abuse, neonaticide, or suicide. 1,2 Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacotherapy for depression, and SSRI use during pregnancy has been well documented.Overall, data regarding the use of SSRIs during pregnancy have been reassuring. Most studies 3-9 have reported relatively consistent findings on the adverse effects of SSRI use during pregnancy, which include neonatal withdrawal syndrome, low birth weight, and preterm birth. Many studies 10-12 have indicated no major fetal malformations higher than the baseline population risk of 1% to 3% with use of SSRIs during pregnancy. One study 13 has indicated increased risks for specific defects, whereas another study 14 noted an association between overall SSRI use during pregnancy and 3 distinct types of birth defects.Congenital heart disease (CHD) is recognized in approximately 0.4% to 1% of all live births, 15-17 and several studies have suggested that use of an SSRI, particularly paroxetine, may be associated with an increased risk of CHD. In particular, ventricular septal defects (VSDs) have been associated with use of paroxetine during the first trimester, 18-22 although a recent meta-analysis 23 that reviewed both previously published and unpublished data did not confirm this association. One report 20 showed a dose response in neonates exposed to paroxetine during the first trimester; infants exposed to paroxetine at dosag...

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Grigoriadis¹,

VonderPorten²,

Mamisashvili³

et al. 2013

J. Clin. Psychiatry

Self Cite

155

117

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Objective: Depression is often not optimally treated during pregnancy, partially because of conflicting data regarding antidepressant medication risk. This meta-analysis was conducted to determine whether antenatal antidepressant exposure is associated with congenital malformations and to assess the effect of known methodological limitations. Data Sources: EMBASE, CINAHL, PsycINFO, and MEDLINE were searched from their start dates to June 2010. Keywords of various combinations were used, including, but not limited to depressive/mood disorder, pregnancy, antidepressant drug/agent, congenital malformation, and cardiac malformation. Study Selection: English language studies reporting congenital malformations associated with antidepressants were included. Of 3,074 abstracts reviewed, 735 studies were retrieved and 27 studies were included. Data Extraction: Two reviewers working independently assessed article quality. Data on use of any antidepressant, including fluoxetine and paroxetine specifically, were extracted. Outcomes included congenital malformations, major congenital malformations, cardiovascular defects, septal heart defects (ventral septal defects and atrial septal defects), and ventral septal defects only. Results: Nineteen studies were above quality threshold and make up the primary meta-analyses. Pooled relative risks (RRs) were derived by using random-effects methods. Antidepressant exposure was not associated with congenital malformations (RR = 0.93; 95% CI, 0.85-1.02; P = .113) or major malformations (RR = 1.07; 95% CI, 0.99-1.17; P = .095). However, increased risk for cardiovascular malformations (RR = 1.36; 95% CI, 1.08-1.71; P = .008) and septal heart defects (RR = 1.40; 95% CI, 1.10-1.77; P = .005) were found; the RR for ventral septal defects was similar to septal defects, although not significant (RR = 1.54; 95% CI, 0.71-3.33; P = .274). Pooled effects were significant for paroxetine and cardiovascular malformations (RR = 1.43; 95% CI, 1.08-1.88; P = .012). These results are contrasted with those addressing methodological limitations but are typically consistent. Conclusions: Overall, antidepressants do not appear to be associated with an increased risk of congenital malformations, but statistical significance was found for cardiovascular malformations. Results were robust in several sensitivity analyses. Given that the RRs are marginal, they may be the result of uncontrolled confounders. Although the RRs were statistically significant, none reached clinically significant levels.

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Evaluation of the Risk of Congenital Cardiovascular Defects Associated With Use of Paroxetine During Pregnancy

Abstract: Paroxetine does not appear to be associated with an increased risk of cardiovascular defects following use in early pregnancy, as the incidence in more than 3,000 infants was well within the population incidence of approximately 1%.

Cited by 161 publications

References 22 publications

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Antidepressant Use in Pregnancy and the Risk for Cardiac Defects

Congenital Heart Disease Associated With Selective Serotonin Reuptake Inhibitor Use During Pregnancy

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

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