Weight regain after obesity drugs tied to higher odds of suicidal thoughts in observational study
A new observational study from South Korea finds that adults using prescription weight-loss drugs report higher rates of depression and suicidal thoughts, with risks climbing among those who regained weight.
Adults who used prescription weight-loss medication in the past year reported significantly higher rates of depression, mental-health counseling, suicidal thoughts, and suicide-related behaviors than people who did not take the drugs, according to a new observational study. The research, conducted at Asan Medical Center in South Korea, analyzed data from 27,741 adults, including 846 people who had taken prescription medications for weight control during the previous year.
The findings, published in the Korean Journal of Family Practice on Aug. 23, showed that weight-loss drug users were 1.9 times more likely to experience depression and twice as likely to seek mental health counseling. They were also 2.7 times more likely to have suicidal thoughts and 1.7 times more likely to make a suicide attempt. The associations were stronger among those who gained or regained weight while using the medications.
“The tendency for depression and suicide-related indicators to increase as weight rebounds after using weight-loss drugs may reflect not only the neuropsychiatric effects of the drugs themselves, but also a complex interplay of psychological and social factors associated with failed weight control,” the research team wrote in the study.
Bonnie Mitchell, a licensed professional clinical counselor in California, noted that the study is observational and cross-sectional, meaning it shows a correlation but cannot prove causation. “It does not demonstrate that weight-loss medications directly induce depression or suicidal thoughts,” she said.
The data was collected between 2013 and 2022, a period when modern GLP-1/GIP receptor agonists such as high-dose semaglutide or tirzepatide were either not yet on the market or had limited real-world uptake in South Korea, Mitchell said. “The study sample captures older anti-obesity agents historically prescribed in South Korea during that decade, including phentermine, diethylpropion, phendimetrazine, topiramate and orlistat.”
Central nervous system stimulants, including phentermine-based drugs, have been shown to carry risks of anxiety, mood changes, and insomnia, the counselor noted. The study also highlighted a striking sub-finding: users who gained weight despite taking the medication had 4.2 times higher odds of suicidal ideation compared to non-users.
Weight regain or perceived failure in weight management can trigger profound guilt, shame, helplessness, and psychological distress, according to Mitchell. “Individuals with severe obesity have higher baseline rates of depression, anxiety and body dysmorphia,” she said. “A cross-sectional survey cannot separate pre-existing mental health struggles from new symptoms that arose after starting a medication.”
More research is needed to determine whether weight-loss medications themselves affect mental health or whether depression and other symptoms are related to factors such as obesity or difficulties losing weight. Researchers also need to determine whether mental health risks differ between specific weight-loss drugs.
Mitchell noted that even though GLP-1 clinical trials show low absolute risk, the FDA’s product labels for chronic weight management drugs like Wegovy and Zepbound include warnings to monitor for mood changes. She recommends that physicians conduct a baseline mental health history before prescribing new weight-loss medications, evaluating past or current depression, bipolar disorder, or history of suicidal ideation or behavior.
“Doctors can inform patients and caregivers about potential mood changes so they know what to watch for,” Mitchell said. “The next important step for ongoing monitoring would be to schedule check-ins at 4- to 8-week intervals during dose escalation, to evaluate both physiological progress and psychological well-being.”
Patients should contact their healthcare provider immediately if they notice new or worsening depressive symptoms. “Any active suicidal thoughts require immediate emergency medical care,” Mitchell advised. “If a patient develops emergent depression or suicidal ideation during treatment, clinicians should discontinue the weight-loss medication and connect the patient with psychiatric support.”
Eli Lilly, manufacturer of the tirzepatide weight-loss medication Zepbound, explicitly mentions “depression or thoughts of suicide” in its safety information. “You should pay attention to changes in your mood, behaviors, feelings or thoughts,” the company’s website reads, advising patients to contact a healthcare provider if mental health changes are “new, worse or worry you.” On its medical-information site, Lilly says that after reviewing clinical trials and medical reports, “no increased risk” of suicidal ideation or psychiatric adverse effects was identified. Novo Nordisk, manufacturer of the semaglutide weight-loss medication, also addresses mental health considerations in its product information.
