GLP-1 drugs and suicidal ideation: conflicting studies, small risk

A new observational study found that people taking Ozempic and Wegovy appeared to experience suicidal thoughts more often than people taking other medications, although experts raised concerns about the methodology and the findings contradict what some other studies have found about the class of GLP-1. medications for diabetes and obesity.

Academic researchers analyzed a World Health Organization database that tracks suspected side effects of medicines and found that there were 45% more reports of suicidal thoughts associated with semaglutide, the ingredient in Novo Nordisk’s Ozempic and Wegovy, compared to all other medicines in the world. database.

When comparing semaglutide specifically to other diabetes and obesity medications — including Farxiga, metformin and orlistat — researchers again saw a higher rate of suicidal ideation reported for semaglutide, according to the studypublished Tuesday in JAMA Network Open.

These observations do not mean that semaglutide caused suicidal thoughts, and the overall percentage of these thoughts was still small: only 0.3% of all reported side effects for semaglutide. Additionally, although semaglutide was associated with a higher rate of suicidal thoughts compared to other drugs in the database, it was linked to a lower rate of behaviors, such as suicide attempts and self-harm.

Notably, the researchers found no higher rates of suicidal ideation linked to an older and less effective GLP-1 drug from Novo called liraglutide, the ingredient in the diabetes treatment Victoza and the obesity therapy Saxenda.

The new study is part of an emerging mixed picture on whether the highly popular GLP-1 drugs are linked to a greater risk of suicidal thoughts. Another observational study saw an increased rate associated with GLP-1 drugs (although not causally related), while other studies do not. The Food and Drug Administration and the European Medicines Agency have investigated the issue, following anecdotal reports of suicidal thoughts, but have so far found no evidence of a causal link.

Some anti-obesity drugs that came before GLP-1 treatments were associated with a greater risk of suicidal thoughts, prompting doctors and regulators to watch for a similar phenomenon when evaluating new anti-obesity drugs. The label for Wegovy – which is approved for obesity – already warns doctors to monitor patients for suicidal ideation; the label for Ozempic – approved for diabetes – is not.

In a statement, Novo said “the known risks associated with the use of these medications are reflected in their current FDA and EMA approved product labeling.” The company said it stands behind the safety and efficacy of its GLP-1 drugs when used as directed, and that it continues to work with regulators to monitor the safety of its treatments.

Novo, as well as outside experts, noted that the new study is limited because it does not take into account variables such as how well patients adhered to treatment, and patients’ diagnoses and medical histories.

Rodrigo Mansur, an assistant professor of psychiatry at the University of Toronto who was not involved in the study, said this issue needs further study and that it is possible that there is a specific subgroup of patients at risk of suicidal thoughts while taking this medicine. the drugs, and not the entire population.

As regulators investigate this issue, researchers are also investigating another potential effect of GLP-1 drugs: whether they can actually help treat mental disorders. Mansoer is running a clinical trial to see if semaglutide can improve cognitive function in people with obesity and major depression.

He said it is not inconceivable that GLP-1 drugs benefit some people with mental disorders while increasing risks for some others – just as standard antidepressants may be helpful for many people but may also increase the risk of suicidal thoughts in others. enlarge.

In the new study, researchers found that a higher rate of suicidal ideation was reported, especially in patients taking both semaglutide and antidepressants – more than four times the rate of other drugs in the database. When researchers excluded these patients from their analysis, semaglutide was no longer linked to a higher rate of suicidal ideation.

There are many possible explanations for this finding. It may be that the combination of semaglutide with antidepressants increases the risk of suicidal thoughts. It may also be that once the people taking both drugs were excluded from the analysis, the sample size was too small to perform meaningful statistical analyses.

Or it could point to a confounding variable: It’s possible that people taking semaglutide were already at greater risk for depression and suicidal thoughts even without semaglutide, since diabetes and obesity are conditions that increase the risk of depression.

Rong Xu, a professor of biomedical informatics at Case Western Reserve University who was not involved in the study, said via email that “the database and method have limitations, all of which are related to unmeasured or uncontrolled confounders.”

Xu said the WHO database used in this new study does not contain comprehensive information on patients’ demographics, lifestyle factors and medical history, all potential confounders that are not fully taken into account in the study. Xu had led another study who found no link between GLP-1 drugs and suicidal ideation, using a different database.

Experts also wondered whether it was the drugs themselves or the weight loss that could lead to suicidal thoughts. When someone loses a significant amount of weight, he or she is going through a significant life change that can impact his or her mental health. Or, if patients expect to lose a lot of weight but don’t, the disappointment can also worsen their mental health, especially since semaglutide’s efficacy is so often highlighted in the media.

Stephen Burgess, group leader at the University of Cambridge’s MRC Biostatistics Unit, who was not involved in the study, said in a statement that “the impact of losing a large amount of weight could have negative emotional consequences. If someone thinks that losing weight is the key to happiness, but losing weight does not bring happiness, could this lead to depression and suicidal thoughts?

“We need to understand whether these results represent a specific side effect of these drugs, or an unusual but tragic consequence of some individuals’ weight loss,” he added.