Safety Profile of Lithium: A Disproportionality Analysis Using the FDA Adverse Event Reporting System

Introduction: Although lithium has long been considered the gold standard for mood stabilization in the treatment of bipolar disorder, growing concerns about its adverse events have significantly undermined its once-trusted status. This study aims to conduct a pharmacovigilance analysis of lithium to provide a more comprehensive understanding of its safety profile.

Four disproportionality analysis methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM), were employed to detect potential signals between lithium and various adverse events.

Analysis of 6,909 adverse event reports from the FDA Adverse Event Reporting System (FAERS) showed that lithium-related adverse events occur in the endocrine, renal or urinary, nervous, and psychiatric systems. Well-known adverse events, such as hypothyroidism, nephrogenic diabetes insipidus, and ataxia, were found. In addition, several previously overlooked adverse events, such as renal oncocytoma, benign parathyroid tumor, and Adams-Stokes syndrome, were identified.

By analyzing real-world data, this study provides a comprehensive evaluation of lithium's safety profile, offering critical evidence for its clinical risk. However, given the inherent limitations of FAERS, such as underreporting of minor symptoms, the findings should be interpreted cautiously.