A recent study published in JAMA Internal Medicine indicates that semaglutide, a popular weight-loss drug marketed as Ozempic and Wegovy, does not increase the risk of depression or suicidal thoughts and behaviors in individuals without pre-existing major mental health disorders. The findings offer reassurance amid growing concerns about the potential psychiatric side effects of these medications, which have seen a surge in popularity for both weight management and type 2 diabetes treatment.
The study, led by researchers at the Perelman School of Medicine, University of Pennsylvania, analyzed data from over 3,500 participants across four major clinical trials funded by Novo Nordisk, the maker of Ozempic and Wegovy. The trials assessed the effects of semaglutide on adults with overweight or obesity. Participants completed mental health questionnaires before and after one to two years of treatment with weekly semaglutide 2.4 mg or placebo.
Key Findings
The analysis revealed that semaglutide did not increase the risk of depression, suicidal thoughts, or suicidal behavior compared to placebo in people without known mental health disorders. Approximately 1% or fewer of the clinical trial participants reported suicidal thoughts or behaviors, with no significant differences observed between those taking semaglutide and those taking a placebo. Moreover, 2.8% of those taking semaglutide developed depressive symptoms, compared with 4.1% of those taking a placebo.
"It is certainly possible that individuals with overweight or obesity who take semaglutide may experience depressive symptoms or suicidal ideation or behavior, but the data suggest that persons not taking semaglutide -- in the placebo group in this study -- are equally likely to experience these conditions," said researcher Gregory Brown, director of the Penn Center for the Prevention of Suicide at the University of Pennsylvania's Perelman School of Medicine in Philadelphia.
Context and Considerations
As many as 5 million Americans were prescribed semaglutide in 2023, with nearly 4 in 10 taking it for weight management. The rise in prescriptions has prompted increased scrutiny of potential side effects, including psychiatric concerns. The FDA has required all medications registered for treatment of obesity since 2012 to assess participants for suicidal ideation or suicidal behavior.
Robert Kushner, MD, professor of Medicine in the Division of Endocrinology said, "Since 2012, the FDA has required all medications registered for treatment of obesity to assess participants for suicidal ideation or suicidal behavior. That’s because of previous medications that have caused those side effects. Not only is it required, but there’s a popular concern: what are the effects on mental health and mood?"
Limitations and Future Research
The researchers emphasized that the study did not include individuals with moderate-to-severe depression, schizophrenia, or bipolar disorder. Therefore, further research is needed to assess the psychiatric effects of semaglutide in patients with pre-existing mental health conditions.
"What we can say, is that if individuals have either mild or moderate depression, it appears to be safe. But what we do not know is whether they truly are safe for individuals who come in with severe depression or a more recent history of suicidal behavior," Kushner said. "We need to be careful and study those individuals going forward. All patients who are being treated with an anti-obesity medication need to be periodically monitored for changes in mood or symptoms of depression."
Implications
While the current findings provide reassurance regarding the psychiatric safety of semaglutide in individuals without major mental health disorders, experts advise continued vigilance and monitoring of mood changes in all patients taking anti-obesity medications. The study underscores the importance of careful patient selection and ongoing assessment of mental health status during treatment with semaglutide.
