New study links using semaglutide drugs like Ozempic to suicidal thoughts

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A new study finds a significant correlation between the use of semaglutide drugs such as Ozempic, antidepressant, or benzodiazepine use, and suicidal ideation.
No such link was found between liraglutide GLP-1 drugs and suicidal ideation.
Other recent research, however, has found no link between semaglutide use and symptoms of depression, or suicidal behaviors, in people with no existing mental health diagnoses.
National health authorities have so far found no connection between GLP-1 medications and suicidal thoughts, but research is continuing.
A new study adds to the conversation regarding the possible effect of GLP-1 diabetes/weight loss drugs on suicide ideation, although its message is a subtle one.
The study finds a disproportionality in the number of people who take semaglutide-based GLP-1 drugs and antidepressants or benzodiazepines and who report suicidal ideation.
benzodiazepines
Glucagon-like peptide 1 (GLP-1) receptor agonist medications were originally developed to help people with diabetes maintain blood sugar levels and a healthy weight.
They have since become popular as weight loss drugs, with Wegovy officially being approved by the Food and Drug Administration (FDA) for this use, as well as Zepbound (tirzepatide) receiving approval from the FDA for weight management in November 2023.
approval from the FDA for weight management
Many of these drugs are based on semaglutide, which was first made available to patients in 2017. These include Wegovy, Ozempic, and Rybelsus, all manufactured by Novo Nordisk.
Among the early GLP-1 drugs still in use is liraglutide. Drugs based on liraglutide include Saxenda and Victoza.
The researchers found no indication of increased suicidal ideation in people who took liraglutide GLP-1 drugs alongside antidepressants.
Experts’ concerns regarding GLP-1 drugs and suicidal ideation stem from three patients reported in Iceland, and 201 similar reports received by the FDA. Since that time, the European Medicines Agency (EMA) and the FDA have investigated the issue.
On January 11, 2024, the FDA released a statement saying it had found no connection between the drugs and suicidal thoughts. In April 2024, EMA did the same.
statement
EMA did the same
In fact, in January 2024, the U.S. National Institutes of Health reported on a study finding people on GLP-1 drugs had less suicidal ideation than other people.
study
What is unusual about the new study, and what it adds to the discussion, is that it found a disproportionality “signal” specifically among people who were taking both semaglutide medications and antidepressants and benzodiazepines.
In arriving at their findings, the authors of the new study analyzed the World Health Organization’s global database of adverse drug reactions that were suspected to be attributable to semaglutide or liraglutide.
The study is published in the JAMA Network Open.
JAMA Network Open
Possible link between GLP-1 drugs and suicidal ideation?
To begin with, lead author Georgios Schoretsanitis, MD, PhD, pointed out to Medical News Today that “the disproportionality signal is a hint and cannot be interpreted as a proxy of severity.”
Georgios Schoretsanitis, MD, PhD
It is not clear how strong the association is, nor does the study in any way demonstrate a causal relationship.
Mir Ali, MD, board certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the study, said:
Mir Ali, MD
“As far as I know, no definite mechanism to link GLP-1 medications and suicidal ideation [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 and try to delineate a possible reason for this.”
Separating existing psychological stressors from those possibly caused by GLP-1 is also difficult.
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:
Ian Douglas, PhD, BSc
“The time at which someone starts a treatment for obesity can itself be correlated with mental health difficulties, and the effects of the medication on weight, whether this is a dramatic reduction in weight, or a disappointing lack of weight reduction, can also trigger changes in mental health.”
“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 action on weight, we ideally need studies that compare people treated with GLP-1 agonists with similar people not receiving them to see if there are differences in their risk of mental health outcomes.”— Ian Douglas, PhD, BSc
Of the NIH study, Douglas said, “I wouldn’t go so far as to say GLP-1 agonists prevent mental health problems based on these findings, but the results are certainly not consistent with a harm.”
Douglas questioned the methodology used in the new study, saying that “individual spontaneous reports of suspected adverse drug reactions […] such as those used in the new study are not an appropriate resource in which to test this hypothesis about GLP-1 agonists.”
Ali expressed a similar concern. “A disproportionality analysis is a quick and inexpensive way to assess whether a certain group is overrepresented or underrepresented in a particular outcome.”
Contradictory evidence on semaglutide and mental health
Moreover, another newly published study, which appears in JAMA Internal Medicine, found no association between semaglutide treatment and suicidal behaviors in users with no history of mental health conditions.
JAMA Internal Medicine
The research, which examined data from four of the five Semaglutide Treatment Effect in People with obesity (STEP) trials, looked for changes in symptoms of depression using the Patient Health Questionnaire-9 (PHQ-9), and for indications of potential suicidal ideation and behavior using the Columbia Suicide Severity Rating Scale.
Columbia Suicide Severity Rating Scale
“Our new analyses provide assurance that the medication, when taken by individuals who are free of significant mental health concerns, does not increase the risk of depression, suicidal thoughts, or suicidal behavior,“ said the lead author of the study, Thomas Wadden, PhD, a professor of Psychology in Psychiatry at the Perelman School of Medicine at the University of Pennsylvania, and the former director of Penn’s Center for Weight and Eating Disorders, in a press release.
Thomas Wadden, PhD
press release
While these findings do provide reassurance, it is important to note that this study may not be entirely free of bias. Several of its authors have declared potential conflicts of interest, as — outside of this study — they are affiliated with companies that commercialize semaglutide drugs, such as Novo Nordisk, Sanofi, Eli Lilly, and AstraZeneca.
This study received funding from the Strategic Research Area Epidemiology program at Karolinska Institutet in Sweden, one of the institutions supporting this research.
How semaglutide users can stay safe
Schoretsanitis said that he and his team suggest “that physicians prescribing semaglutide should inform their patients about the medications’ risks, assess their psychiatric history, and evaluate the mental state of patients before starting treatment with semaglutide.”
“If needed, such as in cases of persisting suicidal ideation or in cases of other relevant mental disorders, the treating physician should involve different specialists, including a psychiatrist and/or clinical psychologists for a psychological and psychiatric evaluation.”— Georgios Schoretsanitis, MD, PhD
Of particular concern with GLP-1 drugs is that some people obtain online prescriptions and receive them by home delivery. “We highly discourage off-label use of semaglutide and without any medical supervision,” said Schoretsanitis.
“One of the reasons most medications are only available by prescription is to make sure they are used appropriately, and this includes potential monitoring for emerging side effects,” added Douglas.
“There is a world of difference,” Douglas said, “in terms of follow-up between being prescribed a medication by a known family physician and a relatively anonymous online operator. There is a vital duty of care for all prescribers to ensure they are available and accessible for follow-up and monitoring.”