Ozempic Does Not Increase Depression Risks, Study Says

Scientists say that semaglutide, a popular injectable weight loss/diabetes drug, does not cause depression or suicidal thoughts in individuals without a mental health condition.

Semaglutide, the active ingredient in weight loss drugs like Ozempic and Wegovy, is a highly sought-after treatment for type 2 diabetes and obesity. Its ability to help people with obesity shed a significant amount of body weight and reduce the risk of obesity-related health conditions has led to an uptick in prescriptions.

For example, according to a recent study, prescription fills for the medication increased by 442% from January 2021 to December 2023.

Despite being an effective tool for weight loss, semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been linked to several serious side effects, including intestinal blockage, hair loss, and suicidal thoughts. Reports of these and other adverse effects prompted the U.S. Food and Drug Administration (FDA) to investigate these medications and assess the need for regulatory action.

Can semaglutide cause suicidal thoughts?

Recent studies investigating one specific side effect — suicidal thoughts or thoughts of self-harm — have shown mixed results.

For instance, one large study found that people using semaglutide had a lower risk of suicidal ideation than those taking non-GLP-1 diabetes/weight loss medications.

Other research published in Annals of Internal Medicine also found no link between semaglutide and suicidal thoughts.

However, a more recent study suggests that people taking semaglutide and antidepressants may face a higher risk of suicidal thoughts or ideation.

Now, new research by scientists from the Perelman School of Medicine at the University of Pennsylvania has found more evidence that the blockbuster weight loss/diabetes drug does not increase the risk of depression or suicidal thoughts and behaviors — at least in people without a mental health condition.

To conduct the study, published on September 3 in JAMA Internal Medicine, the scientists analyzed data from over 3,500 participants in the 68-week Semaglutide Treatment Effect in People with Obesity (STEP) 1, 2, and 3 trials and the 104-week STEP 5 study. They also assessed changes in the participants' depressive symptoms and suicidal thoughts and behavior using the Patient Health Questionnaire-9 (PHQ-9).

The analysis showed that 1% or fewer of participants in the STEP trials experienced suicidal thoughts or behaviors while using semaglutide (2.4 mg).

Moreover, 2.8% of participants taking semaglutide and 4.1% taking a placebo reported experiencing depression at some level. The researchers say these depression rates are similar to those among the general population.

"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 Thomas Wadden, Ph.D., a professor of Psychology in Psychiatry and the former director of Penn's Center for Weight and Eating Disorders, in a news release.

The findings align with another study published on September 3 in JAMA Internal Medicine, which found no association between GLP-1s and an increased risk of depression, suicidal behavior, or self-harm in people with type 2 diabetes.

The study's authors note that their results are similar to the FDA's recent post-marketing analysis which found no evidence that semaglutide causes suicidal ideation or behaviors.

Still, people with major depression, other significant mental health conditions, or a history of attempting suicide were not included in the STEP trials. The scientists say that more research is needed to determine whether semaglutide could increase mental health risks in this population.