Tirzepatide, a dual GIP and GLP-1 receptor agonist, has shown substantial weight loss benefits in adults with obesity, with or without type 2 diabetes. To address concerns about its psychiatric safety, Thomas A. Wadden and colleagues conducted a pooled post hoc analysis of three SURMOUNT trials over 72 weeks.
The analysis included 4,056 adults (mean age 47.2 years; 63% women), with 2,806 receiving once-weekly tirzepatide and 1,250 receiving placebo, alongside diet and physical activity interventions. Tirzepatide doses ranged from 5 to 15 mg. Depression and suicidal risk were assessed using PHQ-9 and the Columbia-Suicide Severity Rating Scale throughout treatment and during a 4-week follow-up.
The following findings were reported:
- Baseline mean PHQ-9 scores were low and similar between groups, at 2.7 in the tirzepatide group and 2.6 in the placebo group, indicating minimal depressive symptoms.
- By week 72, mean PHQ-9 scores decreased to 1.9 among participants receiving tirzepatide and to 2.4 in the placebo group.
- Participants treated with tirzepatide were less likely to shift to more severe categories of depressive symptoms compared with those receiving placebo (18.2% vs 24.3%; p < 0.001).
- A smaller proportion of tirzepatide-treated participants reached a PHQ-9 score of 15 or higher compared with placebo (1.2% vs 2.3%), a level typically warranting referral for mental health evaluation.
- Rates of suicidal ideation were low and identical in both groups, reported in 0.6% of participants.
- Nonfatal suicidal behavior occurred in 0.1% of participants receiving tirzepatide and was not reported in the placebo group.
- The proportion of participants experiencing at least one psychiatric adverse event was similar between the tirzepatide and placebo groups (6.8% vs 8.2%).
- Nervous system disorders were reported at comparable rates in the tirzepatide and placebo groups (15.8% vs 13.0%).
The study authors emphasized the importance of continued monitoring of mental health in individuals with obesity, particularly those with a body mass index above 40 kg/m², due to the high baseline risk of depression and anxiety in this population. They noted that tirzepatide did not increase psychiatric risk and that its rates of suicidal ideation and behavior are similar to those observed with other incretin-based therapies.
In conclusion, the post hoc analysis of the SURMOUNT trials supports the psychiatric safety of tirzepatide in adults with overweight or obesity who do not have major psychiatric disorders. While further studies are warranted in populations with significant mental health conditions, these findings provide reassurance regarding tirzepatide’s safety profile in terms of depression and suicidal risk.
Reference:
Wadden, T. A., Oquendo, M. A., Kushner, R. F., Cao, D., Karanikas, C. A., Kechter, A., & Murphy, M. A. Psychiatric Safety of Tirzepatide in People With Obesity and No Known Major Psychopathology: A Post Hoc Analysis of SURMOUNT. Obesity. https://doi.org/10.1002/oby.70122
Disclaimer: This website is primarily for healthcare professionals. The content here does not replace medical advice and should not be used as medical, diagnostic, endorsement, treatment, or prescription advice. Medical science evolves rapidly, and we strive to keep our information current. If you find any discrepancies, please contact us at corrections@medicaldialogues.in. Read our Correction Policy here. Nothing here should be used as a substitute for medical advice, diagnosis, or treatment. We do not endorse any healthcare advice that contradicts a physician's guidance. Use of this site is subject to our Terms of Use, Privacy Policy, and Advertisement Policy. For more details, read our Full Disclaimer here.
NOTE: Join us in combating medical misinformation. If you encounter a questionable health, medical, or medical education claim, email us at factcheck@medicaldialogues.in for evaluation.