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Taking medications like Ozempic is associated with suicidal thoughts

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Scientists have linked the use of semaglutide to suicidal thoughts. Artem Hvozdkov/Getty Images
  • A new study finds a significant association between taking semaglutide medications such as Ozempic, antidepressants or benzodiazepines and suicidal thoughts.
  • No such association was found between the GLP-1 drug liraglutide and suicidal thoughts.
  • National health authorities have not yet found a link between GLP-1 drugs and suicidal thoughts, but research is ongoing.

A new study adds to the discussion about the possible effects of GLP-1 diabetes/weight loss drugs on suicidal thoughts, but its message is subtle.

The study finds that a disproportionately high proportion of people taking semaglutide-based GLP-1 medications and antidepressants or benzodiazepines report suicidal thoughts.

Glucagon-like peptide 1 (GLP-1) receptor agonist drugs were originally developed to help diabetics maintain their blood sugar levels and weight. Since then, they have become popular as a weight loss agent. Wegovy has been officially approved by the U.S. Food and Drug Administration (FDA) for this purpose, and Zepbound (tirzepatide) has received FDA approval for weight management in November 2023.

Many of these drugs are based on semaglutide, which first became available to patients in 2017. These include Wegovy, Ozempic and Rybelsus, all manufactured by Novo Nordisk.

Early GLP-1 drugs that are still in use include liraglutide. Liraglutide-based drugs include Saxenda and Victoza.

The researchers found no evidence of increased suicidal thoughts in people who took the drug liraglutide (GLP-1) together with antidepressants.

The experts' concerns about GLP-1 drugs and suicidal thoughts stem from three patients reported in Iceland and 201 similar reports received by the FDA. Since then, the European Medicines Agency (EMA) and the FDA have been investigating the issue. On January 11, 2024, the FDA published a opinion on the grounds that no link had been found between the drugs and suicidal thoughts. In April 2024, the EMA did the same.

In fact, the US National Institutes of Health reported in January 2024 on a study The finding that people taking GLP-1 drugs fewer suicidal thoughts than other people.

What is unusual about the new study and its contribution to the discussion is that it found a “signal” of disproportionality specifically in people who were taking both semaglutide medication and antidepressants and benzodiazepines.

To reach their conclusions, the authors of the new study analyzed the World Health Organization's global database of adverse drug reactions suspected of being caused by semaglutide or liraglutide.

The study was published in JAMA network opened.

First, lead author Georgios Schoretsanitis, MD, PhD, pointed out Medical news today“The disproportionality signal is an indication and cannot be interpreted as an indicator of the severity of the situation.”

It is not clear how strong this association is, nor does the study in any way demonstrate a causal relationship.

Mir Ali, MD, board-certified bariatric surgeon and medical director of the MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California, who was not involved in the study, said:

“As far as I know, there is no clear mechanism linking GLP-1 drugs and suicidal thoughts. [has been described].” He also said: “There is disagreement because the incidence [of suicidal ideation] is so rare that it is difficult to accurately assess it and determine a possible cause for it.”

It is also difficult to distinguish existing psychological stress factors from stress factors possibly caused by GLP-1.

Ian Douglas, PhD, BSc, Professor of Pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, who was also not involved in the study, pointed out:

“The timing of when someone begins treatment for their obesity may itself be related to mental health issues, and the effects of medications on weight – whether it's dramatic weight loss or a disappointing lack of weight loss – can also trigger mental health changes.”

“If we want to know whether GLP-1 agonists cause changes in mental health status, either through their direct pharmacological action or indirectly through their effect on weight, we ideally need studies comparing people treated with GLP-1 agonists with similar people who do not receive them to see if there are differences in their risk of mental health problems.”
— Ian Douglas, PhD, BSc

Regarding the NIH study, Douglas said: “Based on these findings, I wouldn't go so far as to say that GLP-1 agonists prevent mental health problems, but the results certainly don't suggest that they are harmful.”

Douglas questioned the methodology of the new study, saying, “Isolated spontaneous reports of suspected drug side effects … such as those used in the new study are not an appropriate source to test this hypothesis about GLP-1 agonists.”

Ali expressed a similar concern. “Disproportionality analysis is a quick and inexpensive way to determine whether a particular group is over- or underrepresented in a particular outcome.”

Shoretsanitis said they recommend “that physicians who prescribe semaglutide should inform their patients about the risks of the drug, obtain their psychiatric history, and assess the mental status of patients before starting treatment with semaglutide.”

“If necessary, such as in the case of persistent suicidal thoughts or other relevant mental disorders, the treating physician should consult various specialists, including a psychiatrist and/or clinical psychologist, for psychological and psychiatric assessment.”
—Georgios Schoretsanitis, MD, PhD

What is particularly worrying about GLP-1 drugs is that some people purchase prescriptions online and have them delivered to their homes. “We strongly advise against off-label use of semaglutide without medical supervision,” said Zhoretsanitis.

“One of the reasons most medicines are available only by prescription is to ensure that they are used appropriately, including possible monitoring for side effects that may occur,” Douglas added.

“There is a world of difference,” Douglas said, “in terms of tracking whether a drug is prescribed by a known GP or a relatively anonymous online provider. There is a fundamental duty of care on all prescribers to ensure that they are available and accessible for tracking and monitoring.”

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