Weight loss drugs that use semaglutide—such as Ozempic, Wegovy and Mounjaro—were not found to be associated with an increased risk of depression, suicidal thoughts or suicidal behavior in a recent analysis.
Fears were previously raised about these drugs after some people reported experiencing depressive or suicidal symptoms after taking them.
But when scientists at the University of Pennsylvania analyzed data from four major clinical trials, they found no correlation between taking semaglutide and symptoms of depression, or suicidal thoughts or behavior.
"Our new analyses provide assurance that the medication, when taken by individuals who are free of significant mental health concerns, does not increase the risk of depression, suicidal thoughts, or suicidal behavior," said lead author Professor Thomas A. Wadden, a psychology and psychiatry specialist, in a statement.
Ozempic, Wegovy and Mounjaro are the brand names for weight loss drugs that use glucagon-like petide-1 (GLP-1) analogs such as semaglutide to help control blood sugar and reduce appetite, helping people with obesity to lose weight and those with type 2 diabetes to better manage their condition.
This analysis looked at data from four major clinical trials—called Semaglutide Treatment Effect in People with obesity (STEP)—involving more than 3,500 participants, funded by the pharmaceutical company that developed semaglutide, Novo Nordisk.
In these trials, people with obesity and no known serious mental health disorders took either semaglutide or a placebo for 68 weeks—one year and three months—cumulatively.
"All four STEP trials did not include participants who had experienced major depressive disorder in the past two years or had bipolar disorder, schizophrenia, or other significant mental illness," Wadden told Newsweek.
"In addition, no participants had a lifetime history of a suicide attempt or present clinically significant suicidal thoughts or behaviors. The drug companies and the FDA believe that it is appropriate, when first testing the safety of a new drug, to exclude persons who could be most vulnerable to adverse side effects, including psychiatric side effects."
Those who took semaglutide did so at a dosage of 2.4mg, the same as Wegovy: the brand name for semaglutide when it is prescribed for weight loss.
Participants in the trial recorded their mental health symptoms using a Patient Health Questionnaire and the Columbia Suicide Severity Rating Scale.
Overall, 1 percent of the participants or fewer reported suicidal thoughts or behavior during treatment, and scientists found no difference between the group taking semaglutide compared to those taking a placebo.
Depressive symptoms—serious enough to warrant evaluation by a mental health professional—were experienced by 2.8 percent of those taking semaglutide and 4.1 percent of the placebo group, which the study authors said were consistent with the risk of significant depression in the general population.
Some previous studies have found associations between semaglutide and suicidal thoughts.
The Food and Drug Administration (FDA) is actively monitoring the psychiatric safety of semaglutide and similar medications.
"The FDA was aware of these data at the time it reviewed and approved semaglutide 2.4mg [Wegovy] for chronic weight management," Wadden told Newsweek. "However, our paper is the first to report these findings to researchers and health professionals in a journal article."
In a statement issued on January 1, 2024, the FDA said that their preliminary evaluation had not found evidence that the use of GLP-1 receptor analogs such as semaglutide caused suicidal thoughts or actions.
Having collected data from patients prescribed with these drugs, and reviewed data from clinical trials, it did not find an association between the use of semaglutide and the occurrence of suicidal thoughts or actions, the website said.
However, it also said it could not rule out that a small risk may exist because a small number of suicidal thoughts or actions had been observed in those using these medications, so the FDA would continue to investigate the issue.
Wadden told Newsweek that the exclusion of people with a history of significant mental illness from the STEP trials meant "carefully controlled examinations are needed of persons who have greater levels of depression and other psychiatric complications" before the drugs are concluded to be completely safe for those people.
Yet he also clarified that patients with a history of depression or another mood disorder whose symptoms were well controlled could be appropriate candidates for semaglutide-based drugs such as Wegovy.
This is because, he said, a 2024 report had shown that approximately 15 percent of those who took part in STEP trials 1, 2, 3 and 5 were taking antidepressants when they enrolled in the studies, but they reported few depressive symptoms.
"Until further carefully conducted studies have been conducted, caution suggests that patients with a history of significant mental illness talk with both their primary care provider (HCP) and their mental health professional before taking the medication," Wadden told Newsweek.
He explained that depressive symptoms could occur while on weight loss drugs because of the link between obesity, weight loss and mental health symptoms.
"It's important to note that people with obesity, particularly severe obesity, are at higher risk of experiencing depression and anxiety disorders than are people of average weight," said Wadden.
"This risk is present when patients are not trying to lose weight, as well as when they may be trying to. The risk of depression is related, in part, to the prejudice and stigma to which people are subjected about their excess weight.
"It is very difficult to isolate whether psychiatric complications in patients with obesity are associated with their distress about their weight, other life stressors, with a personal or family history of psychiatric illness, or with the effects of trying to lose weight or with having successfully lost it."
Wadden told Newsweek that weight loss could result in improvements to physical health and quality of life, and so could improve mental health—but in a small number of people, weight loss could also have a negative effect.
"Excess weight may serve an emotionally protective function in [individuals with a history of trauma], who can experience traumatic anxiety when they lose a large amount of weight in a short period," he said.
"Their relationship with their body may change dramatically, as may their relationships with family and friends.
"Thus, the possibility exists that some individuals could experience such feelings in losing large amounts of weight with weight management medication."
This study was funded by the pharmaceutical company that produces semaglutide-based drugs, Novo Nordisk. Wadden has received grants and consulting fees from Novo Nordisk.
Anyone experiencing depression, or suicidal thoughts or behavior, can call or text 988 or go to the website https://988lifeline.org for support.
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References
Ueda, P., Söderling, J., Wintzell, V., Svanström, H., Pazzagli, L., Eliasson, B., Melbye, M., Hviid, A., & Pasternak, B. (2024). GLP-1 Receptor Agonist Use and Risk of Suicide Death. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.4369
Wadden, T. A., Brown, G. K., Egebjerg, C., Frenkel, O., Goldman, B., Kushner, R. F., McGowan, B., Overvad, M., & Fink-Jensen, A. (2024). 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 Internal Medicine. https://doi.org/10.1001/jamainternmed.2024.4346
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