People who use prescribed weight loss medications face a significantly increased risk of experiencing depression and suicidal thoughts, according to newly published research from scientists in South Korea.
The researchers found that users of the medications had 93 percent higher odds of suffering from depression and 168 percent higher odds of reporting suicidal thoughts when compared with individuals who did not use the drugs.
Furthermore, the scientists discovered that the risk of suffering from severe mental health problems rose substantially over the decade-long tracking period if patients experienced weight regain after being prescribed the medication.
Writing in the Korean Journal of Family Practice, Dr. Ki Young Son and the study's co-authors outlined their findings. "The use of weight loss medications is associated with an increased risk of depression and suicidality," the researchers wrote in the paper. "The risk is further elevated among individuals who experience weight regain after medication use."
FDA warnings and previous concerns
Suicide risk has historically been a major safety concern surrounding the rapidly growing market for weight loss drugs. The United States Food and Drug Administration (FDA) previously received hundreds of reports from patients who stated they began to experience severe despair or suicidal thoughts while taking the medications. In some of these documented cases, the patients had no prior history of mental health problems before starting the treatment.
The modern medications driving the current weight loss boom include highly popular options such as Wegovy, produced by Novo Nordisk, and Zepbound, manufactured by Eli Lilly. Both belong to a class of medications known as GLP-1 receptor agonists. These drugs were initially developed and approved to treat type 2 diabetes by stimulating the pancreas to produce more insulin after meals.
They have since become highly sought after globally for weight management because they mimic naturally occurring hormones that signal fullness to the brain. The medications also slow down the emptying of the stomach, helping patients feel satiated for longer periods and consume significantly fewer calories.
Initially, these modern GLP-1 drugs were required by regulators to carry explicit suicide warnings on their packaging labels. This requirement was a legacy inherited from patients taking much older weight loss treatments who had reported suffering from depression and suicidal ideation. Clinical depression was also previously listed on the warning label alongside the suicide warning, advising patients and their doctors to carefully monitor for any developing psychiatric symptoms.
However, in January of this year, the FDA removed those specific warnings from the GLP-1 medications. At the time, the regulatory agency stated that an extensive review of both clinical trial results and real-world observation data demonstrated no increased risk of suicide among users of the drugs. The warning for depression was also withdrawn simultaneously following the review.
The South Korean study details
For the newly published research, the South Korean scientists analyzed mental health data gathered from 27,000 adults. This expansive cohort included 846 individuals who specifically reported using a prescribed weight loss medication.
The data was drawn from the Korea National Health and Nutrition Examination Survey. This government-backed program is a major, ongoing survey of adults across the country designed to assess the general health and nutritional status of the population. The researchers utilized survey data collected over a nine-year period, spanning from 2013 to 2022.
Across the entire survey group, approximately 60 percent of the adults included in the analysis were female, with an average age of 48 years old. However, the demographics shifted significantly when isolating those taking the medications. Among the weight loss drug users, 90 percent were female, and they had a considerably lower average age of 41 years old. The researchers noted that they adjusted the data in their statistical analysis to properly account for variable factors, including age and gender differences between the user and non-user groups.
The resulting figures highlighted a stark contrast in mental health outcomes. Overall, 22 percent of the weight loss drug users reported suffering from depression, which was exactly double the 11 percent rate seen among those who did not use the medications.
The disparity also extended to suicidal ideation. Nearly 10 percent of the medication users reported suffering from suicidal thoughts, compared to just 4.5 percent among the non-users.
When participants were asked if they had ever actively planned a suicide, 2.2 percent of the weight loss drug users confirmed they had done so, compared to 1.4 percent of the non-users. Additionally, 8.4 percent of the medication users reported that they had sought professional counseling for mental health issues, while only 3.4 percent of non-users had sought similar medical help.
Impact of weight regain
The study did not specify the exact GLP-1 medications that the individual users had taken. However, medications based on both semaglutide, the active compound in Wegovy, and tirzepatide, the active compound in Zepbound, have been officially approved by medical authorities for use in weight loss in South Korea.
In the second part of their study, the researchers shifted their focus to analyze data specifically concerning patients who reported regaining weight after having been initially prescribed the drugs.
The patients in the survey did not state whether they had actively stopped taking the medications before regaining the weight. Obesity is increasingly treated by the medical establishment as a chronic condition requiring long-term management, and separate medical studies have consistently shown that patients who use and then stop taking GLP-1 drugs tend to regain about 60 percent of the weight they lost within a year, on average, as the drug leaves their system and their appetite returns.
The South Korean researchers categorized the amount of weight regain to measure its impact on mental health. They used patients who regained between 6 and 13 pounds after using the GLP-1 drugs as their baseline for comparison.
Compared to that baseline group, the researchers found that patients who reported regaining between 13 and 22 pounds had 65 percent higher odds of reporting suicidal thoughts. This specific group also had 36 percent higher odds of saying they had planned a suicide, and 30 percent higher odds of stating they had sought counseling for mental health problems.
The risks escalated dramatically for those who put on even more weight. Patients who reported regaining more than 22 pounds after using the medications had 267 percent higher odds of reporting suicidal thoughts compared to the baseline group. They also experienced 96 percent higher odds of saying they had planned a suicide, and 70 percent higher odds of having sought mental health counseling.
Interestingly, the researchers noted that patients were no more likely to experience clinical depression when they regained weight after receiving a prescription than if they did not regain the weight, meaning the risk for depression did not seem to compound with weight gain in the same way that suicidal thoughts did.
Observational limitations
While the South Korean study highlights a significant association between the medications and mental health struggles, the broader medical community emphasizes that prior studies have not yet established a definitive, clear link between the drugs and conditions like depression. Researchers frequently note that clinical depression can be caused by a complex multitude of interacting factors.
Furthermore, the scientists acknowledged that their study was observational. Because it relied on survey data, it could identify statistical correlations, but it could not ultimately prove that using GLP-1 drugs directly caused the users to be more likely to suffer from mental health problems than the non-users.
