Studying the Mental Health Impact of Weight Loss Drugs

By

Robert Kushner, MD, professor of Medicine in the Division of Endocrinology, was a co-author of the study published in JAMA Internal Medicine.  

A popular weight loss drug is psychiatrically safe for people without a history of significant mental health disorders, according to a new clinical trial published in JAMA Internal Medicine.

Semaglutide, sold under brand names Ozempic and Wegovy, has shown promise in treating obesity, but the psychiatric effects of the drug have not been well-studied.

Obesity is associated with numerous mental health and social complications, making psychiatric safety a key concern for patients on weight loss drugs, said Robert Kushner, MD, professor of Medicine in the Division of Endocrinology and a co-author of the study.

“Since 2012, the FDA has required all medications registered for treatment of obesity to assess participants for suicidal ideation or suicidal behavior,” Kushner said. “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?”

In the current study, investigators pooled data from four previous international clinical trials studying the effects of semaglutide on adults with overweight or obesity. The analysis included 3,377 participants who had completed a mental health questionnaire before and after a year or two years of treatment with weekly semaglutide 2.4 mg or placebo.

Both groups had no clinically meaningful change in average depression score, however, patients on semaglutide were 37 percent less likely to change to a more severe level of depression than those who received placebo, according to the study.

The results suggest that semaglutide is psychiatrically safe for patients with obesity who have no major history of mental health disorders, Kushner said.

“We had an opportunity to look at participants prospectively and assess them at fixed times regarding their overall mood, depression and thoughts of suicidal ideation or behavior,” Kushner said. “What we found at the end of the study, which is one to two years, is that there was no increased risk of symptoms of depression or suicidal ideation or behavior from placebo versus semaglutide. In general, there’s either no change in depression score or there’s a slight improvement.”

While the results are encouraging, more research is needed to study the psychiatric effects of semaglutide on patients with obesity who have clinically significant depression or other mental health conditions, Kushner said. Patients with moderately-severe or severe depression, schizophrenia or bipolar disorder were not included in the analysis of the trials.

“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.”

Kushner and his colleagues will continue to study the physical and mental effects of semaglutide, he said.

The study was supported by Novo Nordisk.