Risk of congenital anomalies associated with psychotropic medications: a review of neonatal reports in the FDA adverse event reporting System (FAERS)

Purpose: This study investigates the potential association between commonly prescribed psychotropic medications, such as Atypical Antipsychotics (AAs), Selective Serotonin Reuptake Inhibitors (SSRIs), and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), and congenital anomalies in newborns. The analysis uses data from the Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: Spontaneously reported cases of congenital anomalies in newborns (under 28 days old) were extracted from the FAERS database, covering January 2004 to June 2023. Four signal detection methods-Reporting Odds Ratio (ROR), Medicines and Healthcare products Regulatory Agency (MHRA), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS)-were employed to identify signals associated with neonatal deformities caused by specific drugs, ensuring signal stability and reliability.

Results: The FAERS database contains 21,605 reports involving neonates, with 6,208 cases reporting congenital anomalies. Of these, 6,164 cases (99.29%) attributed the adverse events to drugs. The top ten psychotropic drugs associated with neonatal congenital anomalies were venlafaxine, quetiapine, olanzapine, sertraline, citalopram, mirtazapine, duloxetine, paroxetine, aripiprazole, and fluoxetine. Different drug classes showed varying risks of congenital anomalies, with higher signal frequencies observed for cardiac, nervous system, respiratory-thoracic-mediastinal, and musculoskeletal-connective tissue disorders.

Conclusions: Our study suggests that commonly used psychotropic drugs may increase the risk of congenital abnormalities in newborns, necessitating caution for pregnant women. Compared to other psychotropic drugs, the teratogenic effects of aripiprazole and fluoxetine are relatively minor.

Article highlights: Overcoming the Limitations of Clinical Trials in Special Populations: Due to ethical considerations involving pregnant women and newborns, conducting clinical trials is often challenging. Real-world studies are currently one of the most important sources of evidence for evaluating the safety of medication use during pregnancy. Addressing Challenges in International Signal Detection: There is no established gold standard for signal detection, and different countries use varying methods. To minimize the impact of false-positive signals on the results, this study employs a combination of four different methods for signal mining. Advancing Beyond Small Retrospective Cohort Studies and Case Reports: Most current research on the safety of medication use during pregnancy relies on small retrospective cohort studies or case reports. Studies based on large pharmacovigilance databases overcome these limitations. This approach not only captures information on all drugs that may lead to congenital anomalies in newborns but also monitors rare yet significant safety information, providing more comprehensive data support for assessing the safety of medication use during pregnancy.