Fetal Congenital Cardiac and Vascular Disorders Associated with Sertraline Treatment during Pregnancy: Analysis of FAERS Data

Abstract

Objective. Sertraline is one of the most commonly used antidepressants worldwide and is one of the first-choice treatments for depression during pregnancy. This study is aimed at testing the possible association between sertraline intrauterine exposure and congenital cardiac and vascular disorder occurrences by assessing the publicly available US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods. Disproportionality analysis and Bayesian analysis were used to mine FAERS for suspected congenital cardiac and vascular disorder data for sertraline intrauterine exposure from the first quarter of 2004 to the second quarter of 2021. Results. Among the 914 cases of sertraline used with congenital cardiovascular disease in the FAERS database, the reporting areas were mainly in the United States and Europe. The number of adverse events reported every year since 2004 has no many differences. Congenital anomalies are the most frequently reported serious clinical outcome. Among the 69 positive signals detected from 914 cases, 31 were invalid signals, and 38 were valid signals according to criteria. The most common ones are heart disease congenital, atrial septal defect, ventricular septal defect, patent ductus arteriosus, and persistent fetal circulation. Conclusions. Mining FAERS data can analyze and study the adverse reactions of sertraline in a more comprehensive and in-depth manner, thereby effectively reducing the risk of clinical medication.

ReproTox-KG: Toxicology Knowledge Graph for Structural Birth Defects

“…Besides inhibiting the activity of PI3K, LY-294002 increases the expression of DUSP6, a dual specificity phosphatase that dephosphorylates members of the PI3K pathway. The approved antidepressant drug sertraline was reported to induce cardiac and vascular birth defects based on analysis of FAERS [58]. The ReproTox KG subnetwork of cliques/cycles suggests that such adverse birth defects could be mediated via the activation of the dehydrocholesterol reductase DHCR7 and DHCR24.…”

Treatment of depression during pregnancy: a protocol for systematic review and meta-analysis

“…Given the potential risks to the mother and baby, antidepressants are indicated as a first-line treatment for pregnant women with severe depression ( 15 ), whereas non-pharmacological interventions are suitable for mild to moderate cases ( 16 ). Deciding when to start, switch, or stop antidepressants during pregnancy requires careful weighing of the maternal and infant risks related to treatment and the risks related to the illness itself ( 17 ). It is mandatory to compare unfavorable outcomes after intrauterine exposure to antidepressants with those that affect the offspring of women with untreated depression, both to differentiate disease and treatment effects and to provide clinically useful information about the management of women with depression ( 15 ).…”

“…The use of antidepressants during pregnancy is a subject of debate as evidence of adverse fetal and infant outcomes remains inconclusive ( 19 ). Studies have found an association between the use of antidepressants by pregnant women and an increased risk of cardiovascular malformation ( 17 , 20 , 21 ), persistent pulmonary hypertension ( 21 , 22 ), premature birth, low birth weight ( 23 – 27 ) and an increased risk of psychiatric disorders in offspring, including mood disorders, TEA ( 28 ), and ADHD ( 29 , 30 ). There is, to date, a consensus in previous systematic reviews that the increased risk of premature birth and low birth weight is associated with exposure to antidepressants ( 27 ); however, the impact of the antidepressants use in the increased risk of congenital anomalies and miscarriage is unclear ( 15 , 23 ).…”

“…The prescription of drugs during pregnancy remains a common practice, with antidepressants being the class with the greatest increase in indication over time when compared to other drugs associated with potentially harmful neonatal effects ( 32 ). Among pregnant women using antidepressants, 63%-85% use selective serotonin reuptake inhibitors (SSRIs) ( 17 ). Among SSRIs, sertraline is one of the most widely used drugs worldwide and is one of the first-choice treatments for depression during pregnancy ( 33 ).…”

The ethanolic extract of Salvia lachnostachys Benth is not maternotoxic, does not alter reproductive performance, but has teratogenic potential

“…As an example, we can mention duloxetine, which can lead to an increase in the number of abortions [ 15 ], and selective serotonin reuptake inhibitors, which increase the risk of congenital heart diseases, neonatal maladaptive syndrome, or persistent pulmonary hypertension. This is because serotonin is essential for developing all embryonic cells and organogenesis [ 14 , 16 - 18 ]. In view of the above, we consider that allopathic drugs can harm embryonic and fetal development.…”