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Adults who reported using prescription weight-loss medication in the last year had higher rates of depression, mental-health counseling, suicidal thoughts and suicide-related behaviors compared to people who did not take the drugs, according to an observational study.
The research, conducted at Asan Medical Center in South Korea, analyzed data from 27,741 adults (10,908 men and 16,833 women).
Of these participants, 846 had been taking prescription medications for weight control during the previous year, while 26,895 did not take them.
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The 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 using the medications who gained or regained weight.
“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.
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The findings were published in the Korean Journal of Family Practice on Aug. 23.
Bonnie Mitchell, a licensed professional clinical counselor in California, noted that this was an observational, cross-sectional study.
“It shows a correlation between weight-loss drug use and self-reported mental health symptoms, but it cannot prove causation,” she told Fox News Digital. “It does not demonstrate that weight-loss medications directly induce depression or suicidal thoughts.”
The data was collected between 2013 and 2022.
“During most of this period, modern GLP-1/GIP receptor agonists used for weight loss (such as high-dose semaglutide/Wegovy or tirzepatide/Zepbound/Mounjaro) were either not yet on the market or had very limited real world uptake in South Korea,” Mitchell said.
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“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 highlighted a striking sub finding that found users who gained weight despite taking the medication had 4.2 times higher odds of suicidal ideation compared to non-users,” Mitchell noted.
Weight regain or perceived “failure” in weight management can trigger profound guilt, shame, helplessness and psychological distress, according to the expert.
“Individuals with severe obesity have higher baseline rates of depression, anxiety and body dysmorphia,” Mitchell said. “A cross-sectional survey cannot separate pre-existing mental health struggles from new symptoms that arose after starting a medication.”
“Individuals with severe obesity have higher baseline rates of depression, anxiety and body dysmorphia.”
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.
The researchers also need to determine whether mental health risks differ between specific weight-loss drugs.
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“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,” Mitchell noted.
She recommends that a physician conducts 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.”
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Patients should contact their healthcare provider immediately if they notice new or worsening depressive symptoms, including the following.
- Persistent low mood, unexplained sadness or severe fatigue
- Anhedonia (loss of interest in activities once enjoyed)
- Increased anxiety, agitation, panic attacks or extreme restlessness
- Sleep disturbance or insomnia
- New or worsening thoughts of self-harm or suicide
- Marked changes in behavior or personality, reported by friends or family
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“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.”
“Any active suicidal thoughts require immediate emergency medical care.”
Eli Lilly, manufacturer of the tirzepatide weight-loss medication Zepbound, explicitly mentions “depression or thoughts of suicide” in its safety information.
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“You should pay attention to changes in your mood, behaviors, feelings or thoughts,” the website reads.
It further advises patients to contact a healthcare provider if mental health changes are “new, worse or worry you.”
On Lilly’s medical-information site, the company 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 Wegovy, states in its trials that less than 1% of participants experienced suicidal ideation or behavior during treatment. It also says there was “no difference between semaglutide 2.4 mg and placebo.”
Fox News Digital reached out to Lilly and Novo Nordisk for comment.
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