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.