Semaglutide and Depression: What Is the Relationship?


This 2024 APA Annual Meeting poster investigated the relationship between antiobesity agents like semaglutide and depression.


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Semaglutide, a glucagon-like peptide-1 (GLP-1) analog approved for the treatment of type 2 diabetes, was also approved in the US, Europe, the UK, and Canada in once-weekly subcutaneous formulation for weight management in overweight adults with at least 1 weight-related comorbidity and obesity. The only other GLP-1 analog approved for obesity by the FDA, liraglutide, regulates appetite via action on the hypothalamus. While no significant psychiatric adverse effects have been reported with semaglutide compared with placebo thus far, psychiatric adverse effects, including suicidal ideation, have been reported with other GLP-1 receptor agonists.

Presented at the 2024 American Psychiatric Association Annual Meeting, the poster, “Semaglutide: An opportunity or an obstacle? A literature review and case report exploring the relationship between the popular drug and depression,” examined the relationship between antiobesity agents and depression.1

To demonstrate this relationship, investigators presented the case of a 57-year-old woman with a psychiatric history of recurrent major depressive disorder and a medical history of obesity who had worsening depression associated with semaglutide. At initial evaluation, she reported experiencing 6 months of depressive symptoms, including poor appetite. She attributed her decreased appetite to semaglutide, which she had been taking for 4 months, successfully losing 20 lbs. Since starting treatment with semaglutide, she also reported symptoms of decreased gastric motility, including nausea, and constipation, further contributing to her low mood. To target depressive symptoms, her clinicians added vortioxetine to her ongoing treatment regimen. During her 4-week follow-up, she reported only mild improvement in mood and persistent gastrointestinal symptoms, which interfered with her emotional well-being.

The most commonly reported adverse effects associated with semaglutide are gastrointestinal discomfort including nausea, vomiting, diarrhea, and decreased appetite, with potentially severe adverse events including hepatobiliary disorders, and acute pancreatitis. Although current studies do not report psychiatric adverse effects associated with semaglutide, liraglutide has been associated with depression and suicidality.

The investigators noted that many antiobesity agents initially approved for clinical use were eventually withdrawn from global and regional distribution due to adverse effects including psychiatric disturbances, cardiotoxicity, and dependency. This may suggest a link between appetite suppression and mood through involvement of shared brain regions. Assessing these drugs’ neuropsychiatric safety is of utmost importance, especially considering the higher prevalence of neuropsychiatric disorders in obese individuals compared with the general population.

Further research to explore the relationship between semaglutide and depression is needed. Identifying and limiting the impact of antiobesity medications on patients’ social, mental, and physical health. There is also increased interest in using antidiabetic agents in the treatment of Alzheimer disease (AD) and Parkinson disease (PD) due to the identification of possible links between diabetes mellitus (DM) and the development of AD and PD.2-4 There could be a possible mechanistic link between DM, AD, and PD, including inflammation, insulin resistance, and oxidative stress. Available evidence indicates that semaglutide reduces all-cause dementia rates when compared with placebo.5 Overall, investigation into the effects of semaglutide and other antiobestiy agents, besides weight loss, is necessary.

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1. Bhatia GK, Patel S, Ferrer GF. Semaglutide: an opportunity or an obstacle? A literature review and case report exploring the relationship between the popular drug and depression. Poster presented at: 2024 APA Annual Meeting; May 4-8, 2024; New York, NY. Accessed April 25, 2024.,%20May%2005,%202024

2. Cardoso S, Moreira PI. Antidiabetic drugs for Alzheimer’s and Parkinson’s diseases: repurposing insulin, metformin, and thiazolidinediones. Int Rev Neurobiol. 2020;155:37-64.

3. Klimova B, Kuca K, Maresova P. Global view on Alzheimer’s disease and diabetes mellitus: threats, risks and treatment Alzheimer’s disease and diabetes mellitus. Curr Alzheimer Res. 2018;15(14):1277-1282.

4. Yue X, Li H, Yan H, et al. Risk of Parkinson disease in diabetes mellitus: an updated meta-analysis of population-based cohort studies. Medicine (Baltimore). 2016;95(18):e3549.

5. Joshi P, Tampi RR. Can semaglutide help in psychiatry too? Research shows promise for AD and PD. Psychiatric Times. 2024;41(2).

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