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Zepbound ® (tirzepatide) injection
2.5 mg/ 5 mg/ 7.5 mg/ 10 mg/ 12.5 mg/ 15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Can Zepbound® (tirzepatide) cause or worsen preexisting anxiety, panic, manic, or bipolar disorder?
There is no information about tirzepatide causing or worsening anxiety, panic, manic, or bipolar disorders because this has not been studied.
See important safety information, including boxed warning, in the attached prescribing information.
Tirzepatide and Anxiety, Panic, Manic, or Bipolar Disorders
No information about new or worsening anxiety, panic, manic, or bipolar disorders is included in the current US Zepbound (tirzepatide) prescribing information.1 At the time of review, to the extent there was data available on new or worsening anxiety, panic, manic, or bipolar disorders from the tirzepatide clinical trials and postmarketing experience, it did not meet Food and Drug Administration's criteria for clinical significance, causality to the drug, or relevance to patient safety and treatment decisions.2
Patient safety is Eli Lilly and Company’s top priority, and we actively engage in evaluating, monitoring, and reporting safety information for all our medicines. If new information indicates a new safety concern or signal for the product or the class, including postmarketing experience, the prescribing information will be properly updated in alignment with regulatory authorities.2
The efficacy and safety of tirzepatide in patients with anxiety, panic, manic, or bipolar disorders have not been evaluated.
Relevant SURMOUNT Clinical Trial Exclusion Criteria
In the SURMOUNT clinical program for weight management, participants were excluded if they had
- a history of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 years, or
- a current or history within the past 3 months of treatment with medications that may cause significant weight gain including, but not limited to, tricyclic antidepressants, atypical antipsychotics, and mood stabilizers.3-7
Participants with MDD or generalized anxiety disorder whose disease state was considered stable and expected to remain stable throughout the course of the study, in the opinion of the investigator, could be considered for inclusion if they were not on excluded medications. Selective serotonin reuptake inhibitors other than paroxetine were permitted.3-7
Clinical Recommendations
Eli Lilly and Company cannot provide treatment recommendations on the use of tirzepatide in people with comorbid anxiety, panic, manic, or bipolar disorders. The health care practitioner should consider potential risks and benefits of treatment options and monitor appropriately.
Special Warnings and Precautions Related to Suicidal Behavior and Ideation
Suicidal behavior and ideation have been reported in clinical studies with other weight management products.1
Monitor patients treated with tirzepatide for
- the emergence or worsening of depression
- suicidal thoughts or behaviors, and/or
- any unusual changes in mood or behavior.1
Discontinue tirzepatide in patients who experience suicidal thoughts or behaviors.1
Avoid tirzepatide in patients with a
- history of suicidal attempts, or
- active suicidal ideation.1
Enclosed Prescribing Information
References
1Zepbound [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
2US Food and Drug Administration. Frequently asked questions about labeling for prescription medicines for healthcare professionals. Updated April 1, 2024. Accessed August 19, 2024. https://www.fda.gov/drugs/fdas-labeling-resources-human-prescription-drugs/frequently-asked-questions-about-labeling-prescription-medicines
3Jastreboff AM, Aronne LJ, Ahmad NN, et al; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. https://doi.org/10.1056/NEJMoa2206038
4Garvey WT, Frias JP, Jastreboff AM, et al; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-626. https://doi.org/10.1016/S0140-6736(23)01200-X
5Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909-2918. https://doi.org/10.1038/s41591-023-02597-w
6Aronne LJ, Sattar N, Horn DB, et al; SURMOUNT-4 Investigators. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. https://doi.org/10.1001/jama.2023.24945
7Aronne LJ, Horn DB, le Roux CW, et al; SURMOUNT-5 Trial Investigators. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. Published online May 11, 2025. https://www.doi.org/10.1056/NEJMoa2416394
Date of Last Review: May 29, 2025