Depression and suicide/self-injury signals for weight loss medications: A disproportionality analysis of semaglutide, liraglutide, and tirzepatide in FAERS database.

AIMS: Post-marketing surveillance has indicated potential suicide and self-injury signals in patients taking GLP-1RAs for weight management, despite no current psychiatric warnings in labeling. This study evaluated the association between GLP-1RAs and depression/suicide events using FDA Adverse Event Reporting System (FAERS) data. METHODS: A retrospective pharmacovigilance study analyzed FAERS data (2004-2024) using reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) analyses to evaluate depression and suicide/self-injury adverse events for liraglutide, semaglutide, and tirzepatide. RESULTS: Analysis included 8284 reports for liraglutide (n = 3022), 14,435 for semaglutide (n = 4233), and 15,597 for tirzepatide (n = 5722). Significant signals were identified only for semaglutide in both depression (ROR, 1.87; 95 % CI, 1.60-2.20) and suicide/self-injury events (ROR, 1.73; 95 % CI, 1.46-2.04). Effects were consistent across sex groups but most pronounced in ages 18-64. Post-weight management approval saw increased reporting, particularly in European and North American regions. Tirzepatide showed significantly lower mortality rates (0.26 %) compared to other agents. CONCLUSION: Findings identified significant depression and suicidality signals with semaglutide in weight management. For patients requiring weight reduction therapy, particularly those with psychiatric comorbidities, tirzepatide may represent a more appropriate choice based on its superior safety profile.