Semaglutide may increase risk for suicidal thoughts

Key takeaways:

• Individuals with anxiety or depressive disorders on semaglutide may be at a higher risk for suicidal ideations.
• Greater clarification of patient-related risk factors is needed, researchers said.

Adults who take semaglutide may have increased risk for developing suicidal thoughts, according to results from a case-control study published in JAMA Network Open.

Researchers reported significantly higher odds for suicidal ideation among those who took semaglutide (Ozempic/Wegovy, Novo Nordisk) — a glucagon-like peptide-1 receptor agonist — compared with other medications for weight loss or type 2 diabetes. The trend persisted among individuals being treated simultaneously with antidepressants and benzodiazepines.

The findings ultimately show a need “for urgent clarification of patient-related and drug-related risk factors,” according to the researchers.

Preliminary FDA data showed no evidence that weight-loss drugs cause suicidal ideations and aspirations, although the agency said it could not rule out the possibility of a risk entirely.

Healio also previously reported that people receiving semaglutide as an obesity or a type 2 diabetes medication hadlower risk for suicidal ideation compared with those who were receiving a drug that was not a GLP-1 receptor agonist.

However, “typically, patients with suicidality are excluded from clinical trials,” Georgios Schoretsanitis, MD, PhD, from the Zucker School of Medicine at Hofstra University, and colleagues wrote. “Therefore, the reports from clinical trials may be less precise in capturing the risk of suicidal or self-injurious [adverse drug reactions (ARDS)] in later practice.”

In the disproportionality analysis, the researchers used WHO’s global database to assess potential signals for suicidal and self-injurious ARDs tied to semaglutide and liraglutide (Saxenda, Novo Nordisk).

They found that 107 cases and 163 cases of suicidal or self-injurious ARDs tied to semaglutide and liraglutide, respectively, were reported between November 2000 and August 2023.

A significant disproportionality was seen only for semaglutide-associated suicidal ideation (reported OR [ROR] = 1.45; 95% CI, 1.18-1.77) compared with all medications.

This association remained significant in patients with co-reported use of antidepressants (ROR = 4.45; 95% CI, 2.52-7.86) and benzodiazepines (ROR = 4.07; 95% CI, 1.69-9.82) vs. dapagliflozin, metformin and orlistat, “suggesting that people with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,” the researchers wrote.

“The number of reports showed a gradual increase over the years, which may indicate a widening therapeutic scope in obesity and accumulating clinical experience,” they added.

Schoretsanitis and colleagues explained that because the co-reporting between antidepressants and antidiabetics was “negligible,” patients with diabetes or obesity and without psychiatric disorders may not be at an increased risk for suicidal ideations.

There were several study limitations, which included potential selection bias, limited additional adjustments for potential confounders like alcohol use and the researchers’ inability to estimate the incidence of ARDs.

Based on the results, “we believe that a precaution of use in patients with psychiatric disorders or psychological lability could be added in the semaglutide package insert,” the Schoretsanitis and colleagues concluded. “Remarkably, the FDA label of semaglutide for obesity warned to monitor for depression or suicidal thoughts.”