There is no link between the widely used diabetes and obesity medications known as GLP-1 receptor agonists and increased suicidal thoughts, depression or other serious psychiatric harm based on an integrative review of current scientific evidence conducted by researchers at New Mexico State University and the University of Nevada, Las Vegas.
The review, published in the journal Diabetology, traced the earliest concerns raised over GLP-1 RA therapies and found that after subsequent investigations, the medications do not increase psychiatric risk. GLP-1s include medications such as Ozempic, Wegovy, Saxenda and Zepbound.
“GLP-1 RAs have become a cornerstone treatment for Type 2 diabetes and obesity, now used by tens of millions of patients worldwide,” said Jagdish Khubchandani, a professor of public health at NMSU, who co-authored the study with Kavita Batra, executive director of medical research and scholarly activities at the UNLV Kirk Kirkorian School of Medicine.
Reports that GLP-1s might trigger suicidal ideation, depression or anxiety began appearing soon after the medications gained mainstream popularity. Those reports then prompted formal safety reviews by the U.S. Food and Drug Administration and the European Medicines Agency, beginning in 2023.
The research team analyzed five years of mechanistic, pharmacovigilance, observational and regulatory evidence to trace how early reports were investigated and how the scientific and regulatory consensus shifted over time. Earlier this year, the FDA removed its suicidality warning from GLP-1 medications.
“When reports of depression and suicidal thoughts first surfaced with GLP-1 RA use, they came from patients and doctors voluntarily reporting what they saw, and such reports can raise a question, but can’t answer it,” Batra said. “Since then, studies following millions of patients, including a pooled analysis of 91 clinical trials, have found no increase in psychiatric risk. But an answer for millions isn’t an answer for everyone. The right response is to screen and check in with each patient, not to take an effective treatment off the table.”
The review found that early warning signals were largely tied to one drug from selected patient groups, while larger controlled studies often pointed in contradictory directions – something the research team attributes to study design rather than the drugs themselves.
Khubchandani said spontaneous adverse-event reports can be skewed by media attention, by the fact that people with obesity and diabetes already have higher baseline rates of depression and suicidality, and by more frequent medical visits among treated patients that create more opportunities for symptoms to be reported. Controlled studies that account for these factors do not show exceptionally high risks, he added.
Still, the review found that some groups using GL-P1s may need closer monitoring. Patients already taking antidepressants or benzodiazepines showed a substantially amplified reporting signal for suicidal ideation, suggesting that any residual risk may be concentrated among those with pre-existing psychiatric vulnerability rather than the general patient population.
“Depression is more common in people with Type 2 diabetes than in the general population, and it works in both directions: Depression makes diabetes harder to manage, and diabetes makes depression more likely,” Batra said. “So, the mood symptoms a patient reports on any diabetes medication may have been there long before the prescription. That’s exactly why asking about mental health should be a routine part of diabetes care, not a special step reserved for when a drug is under suspicion.”
Khubchandani said the pace of research on GL-P1 medications needs to catch up with their pace of usage, particularly among groups like adolescents, those with serious mental illnesses and other groups underrepresented in clinical trials to date.
“Just like for several other medications, the decision to use GLP-1 RA should include individualized screening of patients for psychiatric history and suicidality before starting treatment, watching more closely for patients with a history of mood disorders or concurrent psychiatric medication use, and educating patients and caregivers to report mood changes promptly,” Khubchandani said.
To read the review, visit https://www.mdpi.com/2673-4540/7/8/144.
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CUTLINE: Jagdish Khubchandani of New Mexico State University and Kavita Batra of the University of Nevada, Las Vegas, co-wrote a study that found no link between GLP-1 receptor agonists and increased suicidal thoughts, depression or other serious psychiatric harm. Courtesy photos