Semaglutide May Raise Suicidality Risk, Study Says

Patients simultaneously taking semaglutide and antidepressants may be at a higher risk of suicide, according to a new study, although more precise data is needed.

Glucagon-like peptide 1 (GLP-1) receptor agonists are first-line treatments for type 2 diabetes, increasingly used for weight loss. Between 2020 and 2023, their use rose by 594% in young people, particularly in women.

While clinical trials suggest that GLP-1s are safe and well tolerated, rare events due to their increasing use could have a public health impact. The medications have been associated with a possible increased likelihood of depression and suicidality, although the findings are contradicting.

The relationship is hard to determine: people with obesity are at a higher risk of depressive disorders, while depression raises the likelihood of developing obesity.

A new study that appeared in JAMA Network Open analyzed the global World Health Organization adverse drug reaction database.

It found that suicidal ideation was disproportionately reported among patients using semaglutide (Ozempic, Rybelsus, Wegovy) but not among those on liraglutide (Victoza, Saxenda). This was especially true for patients with co-reported use of antidepressants and benzodiazepines.

The use of these drugs indicates affective disorders, and people with these conditions are often excluded from premarketing clinical trials.

“We believe that a precaution of use in patients with psychiatric disorders or psychological lability could be added in the semaglutide package insert,” the authors wrote.

In patients with a new onset of depression without other apparent causes, immediate discontinuation of GLP-1s should be considered, they added.

At the same time, some psychiatrists prescribe GLP-1s to reduce weight gained while using antidepressants and antipsychotics, according to the New York Times's survey.

However, the study does not prove that semaglutide causes suicide ideation; it only shows an association.

The authors point out the evidence from bariatric surgeries, suggesting that a history of depression or anxiety is a predictor of suicide risk. Researchers say this may be due to emerging frustration, as patients undergoing the procedure have high expectations, but some have limited resources to deal with mental distress.