Weight-Loss Drugs and Mental Health: What You Need to Know

New medications for weight loss seem to be flying off pharmacy shelves these days. But could they be linked to mental health conditions?

Researchers are looking more closely at possible associations between medications known as GLP-1 drugs (such as Wegovy for weight management and Ozempic for diabetes) and mental health. In an analysis of global data that recently captured headlines, researchers found an association between taking semaglutide, the active ingredient in Ozempic and Wegovy, and suicidal ideation.

And anecdotal reports have suggested some patients are reporting changes in mood, including anxiety, depression and suicidal thoughts, according to a Healthline article describing what some people are calling “Ozempic personality.”

On the other hand, researchers recently published an analysis in JAMA Internal Medicine which concluded that semaglutide did not increase the risk of depression or suicidal ideation. They based their findings on a post-hoc analysis of data from four major clinical trials involving, in total, more than 3,500 patients taking semaglutide 2.4 mg once weekly.

The clinical trials “provide strong evidence that semaglutide 2.4 mg reduces body weight and improves numerous health complications associated with obesity,” Thomas Wadden, PhD, a professor of Psychology in Psychiatry at the University of Pennsylvania’s Perelman School of Medicine and lead researcher on the new study, said in a news release.

“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.”

Those findings mirror what regulators in the United States and Europe have reported. The U.S. Food and Drug Administration found that evidence did not support that GLP-1 medications cause suicidal thoughts or actions, and the European Medicines Agency reached the same conclusion.

A Patients’ Dilemma

If you’re on one of these medications or may be prescribed one, you may be asking yourself the following questions: Is it safe to take? Or are the risks greater than the benefits?

Those questions are of interest to more people as prescriptions for GLP-1s continue to rise. According to a survey by KFF (formerly Kaiser Family Foundation) reported in May 2024, 12% of American adults have taken one or more of the medications.

Considering how much isn’t yet known about weight-loss medications’ impact on mental health, patients, especially those with mental health conditions, should talk about the potential risk of mental health side effects with their primary care physician and/or psychiatrist, according to medical professionals and researchers who have commented publicly on the findings.

Researchers involved in analyses of weight management drugs and mental health have suggested that patients with a mental health condition should exercise caution.

“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,” Penn’s Dr. Wadden told Newsweek.

In addition, “People with obesity should be monitored for mental health concerns so they can receive appropriate support and care,” the researchers noted in the article published in JAMA Internal Medicine.

Nora Volkow, MD, director of the National Institute on Drug Abuse, told online publication Everyday Health that patients should be screened for mental health conditions before taking GLP-1 drugs.

“It is important for clinicians to continue screening for suicidal ideations and mental health conditions in patients with obesity and diabetes so that proper support can be given to those at risk and harmful health outcomes can be prevented,” Dr. Volkow said.

Exclusions in Clinical Trials

One reason further study is needed is that clinical trials for semaglutide didn’t include people with known mental health conditions.

Novo Nordisk, the company that submitted semaglutide to the FDA for approval, screened patients for mental health. They excluded those with major depressive disorder within the previous two years, as well as those reporting certain other severe or recent mental health conditions, according to the article published in JAMA Internal Medicine.

The authors of the study suggest that, while there is data to support that semaglutide was both safe and effective for those taking an antidepressant at their baseline visit, “controlled investigations and continued postmarketing surveillance are needed to assess the safety and effectiveness of [these weight management medications] in people with obesity and major psychopathology.”

Also, it’s important to know the active ingredient in the weight-loss drug you’re taking. The study published in JAMA Internal Medicine focused only on semaglutide, the active ingredient in Wegovy and some other weight management medications. Other approved weight-loss medications include Saxenda, which has liraglutide as its active ingredient, and Zepbound, with tirzepatide as the active ingredient.

Authors of the study that found an association between semaglutide and suicidal ideation, did not find the corresponding link in their analysis of liraglutide.

The bottom line if you’re taking a weight-management medication: There are many benefits for those with obesity or diabetes, but you should also talk to your physician or mental health professional and pay attention to any changes in your mental well-being. And if you and your clinician are considering medication as part of your treatment plan for your mental health, it may be helpful to discuss use of the GeneSight test with your clinician. The GeneSight test analyzes clinically important genetic variations in your DNA, and the results, along with other clinical and patient specific factors, can be used to help inform your healthcare provider’s treatment decisions for mental health medications.

“All patients who are being treated with an anti-obesity medication need to be periodically monitored for changes in mood or symptoms of depression,” Robert Kushner, MD, a professor of medicine at Northwestern University and a co-author of the study published in JAMA Internal Medicine, said in a story published by Northwestern Medicine.