FDA Reports No Link between Weight-Loss Drugs and Suicidal Thoughts

The Washington Post

17:51 JST, January 12, 2024

Popular drugs used for weight loss do not appear to spark suicidal thoughts in patients, according to a preliminary review conducted by the Food and Drug Administration following reports of potential safety concerns.

The finding Thursday came barely a week after the agency said it was evaluating the need for regulatory action on the drugs – sold under brand names including Mounjaro, Ozempic, Wegovy and Zepbound – because of possible side effects, including thoughts of suicide. The drugs are part of a class of medicine called glucagon-like peptides, named for the natural hormones they mimic and also known by the abbreviation GLP-1.

The FDA said Thursday that it had conducted “detailed reviews of reports of suicidal thoughts or actions” from its system that collects accounts of patients having bad reactions to drugs. “We determined that the information in these reports did not demonstrate a clear relationship with the use of GLP-1” drugs, according to an agency statement.

The FDA also reviewed data from clinical trials that found no link between the drugs and suicidal thoughts or actions. The FDA cautioned, however, that “we cannot definitively rule out that a small risk may exist.”

The drugs have become cultural touchstones, popular with influencers but often short in supply – leading to a proliferation of knockoffs and sales from pharmacies making copies of the drugs. Doctors, pharmaceutical companies and regulators stress that the drugs are safe and, for most patients, do not pose a significant risk to mental health. The FDA’s findings come days after the release of a study conducted in part by the National Institute on Drug Abuse that reached a similar conclusion.

Well-established side effects of the drugs include constipation, nausea and vomiting. Still, regulators have been monitoring their potential impact on mental health for months.

The European Medicines Agency, the continent’s equivalent of the FDA, announced in July it was investigating reports of patients taking drugs such as Ozempic and Wegovy and having suicidal thoughts. It said in December that while “no conclusion can be drawn” yet on whether the drugs cause such a condition, “there are several issues that still need to be clarified.” The European watchdog agency plans to hold another meeting on the topic in April.

On Jan. 2, the FDA said it was investigating reports that the drugs were associated with thoughts of suicide, blockage of lung pathways and the hair-loss condition alopecia. The drugs included Ozempic, Rybelsus and Wegovy, whose main ingredient is a compound known as semaglutide; Mounjaro and Zepbound, made with tirzepatide; and Saxenda and Victoza, made from liraglutide.

The drugs spur the pancreas to produce a naturally occurring hormone known as glucagon-like peptide 1, or GLP-1, that lowers blood sugar and signals to the brain a sensation of feeling full. In addition to activating the GLP-1 hormone, tirzepatide also targets another similar hormone known as GIP.

The agency said it was “evaluating the need for regulatory action” based on reports from patients taking the drugs who said they had experienced health issues. FDA prescribing labels for Wegovy and Zepbound – approved to treat obesity – say suicidal behavior and ideation have been reported in clinical trials for other weight-management drugs. Yet Mounjaro and Ozempic, which contain the same active ingredients but are approved by the FDA for diabetes, don’t contain such warnings.

“At this time, the FDA maintains that the benefits of these medications outweigh their risks when they are used according to the FDA approved labeling,” the agency said Monday, before releasing its preliminary finding.

Novo Nordisk, which makes Ozempic and Wegovy, said in a statement that its semaglutide and liraglutide products have been on the market for years, and it “stands behind the safety and efficacy” of them “when used as indicated.” Eli Lilly, maker of Mounjaro and Zepbound, said the “medicines continue to be monitored by the FDA and manufacturers for safety” even after clinical trials and agency approval.

Experts caution that it is not unusual for drugs to appear in the FDA’s adverse effects database, especially as more patients use them. Millions of patients take Ozempic, Wegovy and similar drugs.

Days after the FDA announced it was investigating possible adverse effects of the drugs, the National Institute on Drug Abuse issued a news release detailing a major study that may have eased concerns about the risk of suicide.

The study, published Jan. 5 in Nature Medicine, found no higher risk of suicidal thoughts among patients taking semaglutide for weight loss or diabetes.

Researchers from Case Western Reserve University School of Medicine and the National Institute on Drug Abuse analyzed millions of electronic health records for more than 240,000 patients prescribed Wegovy or other weight-loss drugs over a six-month period. Patients on Wegovy had a 49 to 73 percent lower risk of suicidal thoughts compared with those taking other classes of weight-loss drugs.

Some researchers not involved in the study urged caution about reading too much into the Nature Medicine study.

Thomas J. Moore, a professor at the Center for Drug Safety and Effectiveness at Johns Hopkins Bloomberg School of Public Health, pointed out that a significant percentage of patients on semaglutide in the study had been taking potent psychiatric medications with known risks for suicidal ideation – and that use of such medications was even higher among subjects taking the other anti-obesity drugs, potentially muddying the picture. He added that he does not believe the records analyzed are comprehensive enough to reach conclusions about the risks of suicidal ideation.

While research still suggests suicide and suicidal thoughts are rare, Moore said, he urged doctors to remain open-minded. “Physicians should investigate and not dismiss patient complaints” about psychiatric side effects, Moore said.

Mental heath is intertwined with the treatment of obesity. Patients may despair if they can’t shed enough pounds with drugs – or suffer a loss of identity if they lose too much weight too quickly. Some research shows patients who have undergone bariatric surgery are at a greater risk of suicidal thoughts.

Doctors and patients have largely reported that the medications boost mental health for many patients who found success with the drugs after struggling with dieting. Jennifer Duncan, a clinical psychologist who works with obesity and diabetes patients at Cleveland Clinic, said her patients have not reported that the drugs imperil their mental health.

“I’ve really seen these medications have a significant impact positively on patients that can get it,” Duncan said. “I think the most distress that I see in patients is frustration with their insurance companies not covering it, or that they’ve had to discontinue the medications because they’re too expensive.”

The medications dull the “food noise” in the brain – obsessive thinking about food that wreaks havoc long-term on a patient’s psyche, Duncan said. “Patients will be like, ‘Oh my gosh, I didn’t realize how much food controlled my life,'” she said.

In the same way GLP-1 drugs signal to the brain a feeling of being full, they may act similarly with alcohol, tobacco and other addictive substances. Clinical trials are underway to gauge how semaglutide affects alcohol and tobacco use.

Researchers say the medications may affect neural receptors tied to the dopamine reward center in the brain that has been hijacked by those addictive substances, said Joseph Schacht, a University of Colorado neuroscientist running a clinical trial to gauge whether semaglutide affects alcohol cravings compared with a placebo. The trial was sparked by anecdotal, if compelling, reports.

“The patients are saying they’ve lost interest in alcohol, that they’re not thinking about drinking all the time, that they are better able to control urges or cravings,” Schacht said.