THE PSYCHIATRIC EFFECTS RESULTING FROM THE USE OF TIRZEPATIDE
DOI:
https://doi.org/10.63330/aurumpub.024-041Keywords:
Tirzepatide, GLP-1, GIP, Psychiatric effects, Mood, ObesityAbstract
Tirzepatide is a dual agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, indicated for the treatment of type 2 diabetes mellitus and obesity, with well-established metabolic efficacy in the scientific literature. However, questions have been raised about potential psychiatric effects associated with its use, including mood changes, anxiety symptoms, apathy, and suicidal ideation. This study performs a critical analysis of the available evidence, distinguishing data from controlled clinical trials, pharmacovigilance systems, and observational studies. Additionally, plausible neurobiological mechanisms that could mediate such effects are discussed, as well as their implications for clinical practice. It is concluded that there is no robust evidence to support a direct causality between tirzepatide and the development of severe psychiatric disorders. However, indirect emotional changes may occur in vulnerable subgroups of patients, which requires the implementation of adequate clinical monitoring.
Downloads
References
1. 1. Asfor, A. C.; Oliveira, T. R.; Sousa Lima, M. E. Eventos adversos neuropsiquiátricos relacionados ao uso de agonistas do receptor de GLP-1: Uma revisão sistemática. Diálogos Interdisciplinares em Psiquiatria e Saúde Mental, [S. l.], v. 4, n. supl. 1, p. e16811, 2025. DOI: 10.59487/2965-1956-4-16811. Disponível em: https://revistas.uece.br/index.php/dipsm/article/view/16811. Acesso em: 9 jan. 2026.
2. Di Stefano R, Rindi LV, Baldini V, Rossi R, Pacitti F, Jannini EA, Rossi A. Glucagon-Like Peptide-1 receptor agonists, dual GIP/GLP-1 receptor agonist tirzepatide and suicidal ideation and behavior: A systematic review of clinical studies and pharmacovigilance reports. Diabetes Metab Syndr. 2025 Apr;19(4):103238. doi: 10.1016/j.dsx.2025.103238. Epub 2025 May 13. PMID: 40388845. Disponível em: https://www.sciencedirect.com/science/article/pii/S1871402125000554?via%3Dihub. Acesso em: 9 jan. 2026.
3. Eli Lilly And Company. Can Zepbound® (tirzepatide) cause or worsen preexisting anxiety, panic, manic, or bipolar disorder? Indianapolis: Eli Lilly and Company, 2025. Disponível em: https://medical.lilly.com/us/products/answers/can-zepbound-tirzepatide-cause-or-worsen-preexisting-anxiety-panic-manic-or-bipolar-disorder-286586. Acesso em: 9 jan. 2026.
4. Gu S. Adverse Events Associated with Tirzepatide: Updated Pharmacovigilance Analysis Using FAERS (2022 Q1-2025 Q1) with an Adapted Time-to-Onset Method. Drug Healthc Patient Saf. 2026 Jan 8;18:556918. doi: 10.2147/DHPS.S556918. PMID: 41531800; PMCID: PMC12989282. Disponível em: https://www.dovepress.com/adverse-events-associated-with-tirzepatide-updated-pharmacovigilance-a-peer-reviewed-fulltext-article-DHPS. Acesso em: 9 jan. 2026.
5. Kornelius E, Huang JY, Lo SC, Huang CN, Yang YS. The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy. Sci Rep. 2024 Oct 18;14(1):24433. doi: 10.1038/s41598-024-75965-2. Disponível em: https://www.nature.com/articles/s41598-024-75965-2. PMID: 39424950; PMCID: PMC11489776. Acesso em: 9 jan. 2026.
6. Mergulhão, Alyson Oliveira et al. EFEITOS NEUROPROTETORES DA SEMAGLUTIDA E TIRZEPATIDA DURANTE TRATAMENTO DE OBESIDADE E DIABETES MELLITUS TIPO 2. ARACÊ, [S. l.], v. 7, n. 11, p. e10171, 2025. DOI: 10.56238/arev7n11-226. Disponível em: https://periodicos.newsciencepubl.com/arace/article/view/10171. Acesso em: 9 jan. 2026.
7. Meshkat S, Di Luciano C, Swiderski A, Li G, Aguilar RJ, Dunkley BT, Reichelt AC, Zhang Y, Greenshaw A, Vermetten E, Jetly R, Dash S, Agarwal SM, Swainson J, Bhat V. Efficacy and Safety of Glucagon-Like Peptide-1 Agonists for Psychiatric Symptoms: A Systematic Review. Brain Behav. 2025 Jul;15(7):e70661. doi: 10.1002/brb3.70661. Disponível em: https://onlinelibrary.wiley.com/doi/10.1002/brb3.70661. PMID: 40635383; PMCID: PMC12241715. Acesso em: 9 jan. 2026.
8. Müller Alves K, Teixeira da Silva M, Kramer CK, Viana LV. GLP-1R Agonists for Weight Loss in Psychiatric Disorders: A Systematic Review and Meta-analysis. J Endocr Soc. 2025 Nov 11;9(12):bvaf150. doi: 10.1210/jendso/bvaf150. PMID: 41230025; PMCID: PMC12602866. Disponível em: https://academic.oup.com/jes/article/9/12/bvaf150/8320247. Acesso em: 9 jan. 2026.
9. O'keefe, J. H.; Franco, W. G.; O'keefe, E. L. Anti-consumption agents: Tirzepatide and semaglutide for treating obesity-related diseases and addictions, and improving life expectancy. Progress in Cardiovascular Diseases, v. 89, p. 102-112, 2025. DOI: 10.1016/j.pcad.2024.12.010. Disponível em: https://www.sciencedirect.com/science/article/pii/S0033062024001798?via%3Dihub. Acesso em: 9 jan. 2026.
10. Pierret ACS, Mizuno Y, Saunders P, Lim E, De Giorgi R, Howes OD, McCutcheon RA, McGowan B, Sen Gupta P, Smith D, Ismail K, Pillinger T. Glucagon-Like Peptide 1 Receptor Agonists and Mental Health: A Systematic Review and Meta-Analysis. JAMA Psychiatry. 2025 Jul 1;82(7):643-653. doi: 10.1001/jamapsychiatry.2025.0679. PMID: 40366681; PMCID: PMC12079569. Disponível em: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2833558. Acesso em: 9 jan. 2026.
11. Wadden, T. A.; Brown, G. K.; Egebjerg, C. et al. Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials. JAMA Internal Medicine, Chicago, v. 184, n. 11, p. 1290-1300, 2024. DOI: 10.1001/jamainternmed.2024.4346. Disponível em: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2823084. Acesso em: 9 jan. 2026
12. Yu W-S, Huang J-Y, Lo S-C, Huang C-N, Yang Y-S and Kornelius E. (2025) Association of tirzepatide and the risk of suicide in a real-world cohort. Front. Psychiatry 16:1626103. doi: 10.3389/fpsyt.2025.1626103. Disponível em: https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1626103/full. Acesso em: 9 jan. 2026.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
