Investigating the Link Between Semaglutide and Suicidal Ideation

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SPECIAL REPORT: ADVANCES IN PSYCHIATRY

Semaglutide has garnered much attention due to its successes regarding weight loss, but what role should it play in patients with serious mental illness who struggle with weight loss?

In their 2024 APA Annual Meeting poster “Semaglutide-Induced Suicidal Ideation in a Patient With Psychiatric Comorbidities: A Case Report,” Raju Kakarlapudi and colleagues shared the story of a 42-year-old woman with type 2 diabetes mellitus who was morbidly obese.¹

Because of the patient’s significant psychiatric history of bipolar I disorder and posttraumatic stress disorder, bariatric surgery was contraindicated. Instead, semaglutide (Ozempic) was considered a suitable alternative to assist the patient with her weight-loss journey.

Within 3 weeks of starting the medication, the patient began to experience significant psychiatric disturbances, including abrupt behavioral alterations and protracted nihilistic delusions, the researchers reported. The patient had several attempts of self-strangulation. These behavioral changes were ameliorated after the patient discontinued the weight loss agent.¹

Kakarlapudi and colleagues wrote in the poster that “the primary aim [was] to augment awareness regarding the potential adverse effects associated with Ozempic utilization, both among the general populace and within the psychiatric community.”¹ To do so, they conducted a literature review and analysis via Google Scholar, looking at studies since 2018. Studies included patient data obtained via direct clinical interviews and behavioral monitoring. The researchers looked for observable trends among pharmacological interventions.

The researchers found approximately 60 documented cases of suicidal ideation and 7 suicide attempts associated with semaglutide use in patients. According to the researchers’ analysis, many patients reported significant improvement in depression after discontinuing the agent. Thus, Kakarlapudi et al concluded that the drug may induce depression in some patients, which could ultimately lead to suicidal ideation.¹

Approved by the US Food and Drug Administration for the treatment of type 2 diabetes in 2017, the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide mimics the GLP-1 hormone, which promotes the production of insulin as a result of eating. GLP-1 receptors “act on the brain stem, lateral septum, and hypothalamus, modulating food intake and reward with GLP-1 receptor stimulation promoting dopaminergic neuron activity at the ventral tegmental area and increased expression of dopamine transporters on neuronal cell surfaces, thereby reducing free dopamine levels in synapses prompting reduced dopamine levels,” Kakarlapudi et al explained.¹

There are 3 semaglutide products approved by the FDA. Wegovy injection is approved for weight loss in 2021 for patients 12 years or older who are obese and for adults who are overweight and have a medical condition related to excessive weight. Ozempic injection and Rybelsus tablets are approved to reduce blood sugar in adult patients with type 2 disease. Additionally, Ozempic is approved to reduce the risk of cardiovascular issues (eg, stroke, heart attack) in patients with type 2 diabetes and heart disease.²

Semaglutide has garnered interest from clinicians, researchers, and patients alike due to its success in helping patients lose weight. Additional posters at the APA meeting explored its usefulness vs potential adverse effects, including low mood.^3,4 Yet, because of its neuroprotective properties, there also is speculation that it may have potential use for patients with Alzheimer disease.⁵ It therefore becomes even more important to better understand the benefits and risks, especially for patients with psychiatric disorders.

“Numerous studies have illuminated the complications associated with GLP-1 medication in patients with psychological disorders,” Kakarlapudi et al wrote. “Further research to identify the specific proteins and enzymes implicated in exacerbating current psychological conditions and inducing such ideations [is warranted].”¹

References

1. Kakarlapudi R, Syed SA, Abbasi M, Jafary Z. Semaglutide-induced suicidal ideation in a patient with psychiatric comorbidities: a case report. Poster presented at: 2024 APA Annual Meeting; May 4-8, 2024; New York, NY. Accessed May 5, 2024. https://s7.goeshow.com/apa/annual/2024/poster_search.cfm?session_key=8E8DFE6F-90B1-1C06-DFD2-CA2230FD8375&session_

2. Medications containing semaglutide marketed for type 2 diabetes or weight loss. FDA. January 10, 2024. Accessed May 5, 2024. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type-2-diabetes-or-weight-loss

3. Kuntz L. Semaglutide and depression: what is the relationship? Psychiatric Times. May 5, 2024. Accessed May 5, 2024. https://www.psychiatrictimes.com/view/semaglutide-and-depression-what-is-the-relationship

4. 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 May 5, 2024. https://s7.goeshow.com/apa/annual/2024/poster_search.cfm?session_key=8E8E03C5-90B1-1C06-DFD2-56B4A81EDBC0&session_

5. Joshi P, Tampi RR. Can semaglutide help in psychiatry too? Research shows promise for AD and PD. Psychiatric Times. 2024;41(2):1;8-10.