Semaglutide And Mental Health

4 min

Semaglutide, which we commonly know by the brand names Ozempic, Wegovy, and Rybelsus, is a GLP-1 agonist. That class of drugs was developed to act like glucagon-like peptide 1 (GLP-1), a hormone that regulates levels of blood sugar and insulin, as a treatment for type 2 diabetes. According to a March 2025 Gallup poll, some 15.5 million Americans have used or are using one of these new injectable medications, with half of them using the drugs for weight loss. Semaglutide is now being studied for potential benefits in Parkinson’s disease, Alzheimer’s disease, and polycystic ovary syndrome. Its relationship with mental health conditions, including anxiety and depression, is not yet well understood – the answer to your question is: it may be associated with either relieving or causing depression.

When a drug becomes as widely used as semaglutide, researchers have the opportunity to search for trends that may not have been noticeable in smaller populations or that weren’t discernable during its development and approval. In the United States, the Food and Drug Administration (FDA) maintains the FDA Adverse Event Reporting System (FAERS) database   to gather information on adverse effects and errors; EudraVigilance is the equivalent in Europe. Adverse drug effects can be as minor as a sore arm after receiving a shot or as major as death.

Alerted by reports of depression and suicidal ideation in patients taking GLP-1 agonists, researchers reviewed slightly more than two years’ worth of European data. They found that 372 of the13,444 total adverse effects in the database were psychiatric in nature – primarily depression, anxiety, and suicidal thoughts, with 9 of them resulting in death from suicide. In response to that, researchers evaluated 18 years’ worth of FDA data in the United States and found an increased incidence of depression and suicidal ideation in those using GLP-1 based products, but not of attempted or completed suicides. Yet another team used a private database called TriNetX and found that those using GLP-1 agonists had nearly double the risk of psychiatric disorders – including major depression, anxiety, and suicidal behavior – than those who did not. These are alarming results, requiring further study.

On the other hand, some studies have found that individuals who lose weight on GLP-1 agonists report an improvement in their mental health. Two independent teams evaluating Epic patient databases (software programs that track electronic heath records) looked at the data of 3 million diabetic patients and nearly a million non-diabetic patients and found that, in both groups, those taking the drugs had a reduced incidence of depression and anxiety compared to those who did not.

Researchers at the University of Pennsylvania who studied records of more than 3,600 patients enrolled in clinical trials of Semaglutide found no increase in depression or suicidal ideation in those without a previous history of mental health issues. (They excluded those who had known mental health diagnoses prior to taking the drug.) That raises the question of whether the drug has a different effect, or additional effects, on those with a pre-existing mental health condition.

This is a complicated issue. I would advise anyone considering one of these drugs to have a candid conversation with your prescribing doctor before beginning GLP-1 based therapy. Any history of depression or other mental health disorder needs to be carefully evaluated before starting on the drug.

See also: Semaglutide and Alzheimer’s Disease

Andrew Weil, M.D.

Sources
McIntyre RS, Mansur RB, Rosenblat JD, Kwan ATH. “The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS).” Expert Opin Drug Saf. 2024 Jan;23(1):47-55. doi: 10.1080/14740338.2023.2295397. Epub 2023 Dec 19. PMID: 38087976. pubmed.ncbi.nlm.nih/38087976/

Tobaiqy M, Elkout H. “Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database.” Int J Clin Pharm. 2024 Apr;46(2):488-495. doi: 10.1007/s11096-023-01694-7. Epub 2024 Jan 24. PMID: 38265519; PMCID: PMC10960895. pubmed.ncbi.nlm.nih/38265519/

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. PMID: 39424950; PMCID: PMC11489776.  pubmed.ncbi.nlm.nih/39424950/

Witaszek T, Babicki M, Brytek-Matera A, Mastalerz-Migas A, Kujawa K, Kłoda K. “Maladaptive Eating Behaviours, Generalised Anxiety Disorder and Depression Severity: A Comparative Study between Adult Women with Overweight, Obesity, and Normal Body Mass Index Range.” Nutrients. 2023 Dec 26;16(1):80. doi: 10.3390/nu16010080. PMID: 38201910; PMCID: PMC10780963. pubmed.ncbi.nlm.nih/38201910/

de Paiva IHR, da Silva RS, Mendonça IP, de Souza JRB, Peixoto CA. “Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis.” J Neuroimmune Pharmacol. 2024 Jul 23;19(1):36. doi: 10.1007/s11481-024-10142-w. PMID: 39042202. pubmed.ncbi.nlm.nih/39042202/

Li JR, Cao J, Wei J, Geng W. “Case Report: Semaglutide-associated depression: a report of two cases.” Front Psychiatry. 2023 Aug 29;14:1238353. doi: 10.3389/fpsyt.2023.1238353. PMID: 37706035; PMCID: PMC10495976. pubmed.ncbi.nlm.nih/37706035/

Wadden TA, Brown GK, Egebjerg C, Frenkel O, Goldman B, Kushner RF, McGowan B, Overvad M, Fink-Jensen A. “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 Intern Med. 2024 Nov 1;184(11):1290-1300. doi: 10.1001/jamainternmed.2024.4346. PMID: 39226070; PMCID: PMC11372653. pubmed.ncbi.nlm.nih/39226070/