Should Ozempic come with a warning about a risk of suicidal thoughts?

Following reports of self-injury and suicidal thoughts among a small number of people who’ve taken Ozempic or Wegovy in Europe and the United Kingdom, health regulators there are investigating whether the drugs carry a risk of these side effects.

The European Medicines Agency said last month that it was reviewing 150 such reports from people who took drugs in this class, called GLP-1 receptor agonists, which lower blood sugar and suppress appetite by mimicking a hormone in the gut.

Then last week, the U.K.’s Medicines and Healthcare products Regulatory Agency told Reuters that it was reviewing safety data about the drugs following similar reports.

Neither Ozempic nor Wegovy, which are both versions of a drug called semaglutide at different dosages, carry warnings about suicidal ideation in Europe or the U.K., since clinical trials have not shown evidence of an increased risk.

But in the United States, the Food and Drug Administration requires that medications for weight management that work on the central nervous system carry a warning about suicidal thoughts. Because the agency approved Wegovy as a weight loss treatment, its prescribing label asks medical professionals to monitor for these symptoms and to discontinue the medication if people develop them. Ozempic, which is only FDA-approved to treat diabetes, does not come with that warning.

But some patients think it should.

Megan Stainer, a 45-year-old nurse who lives in Hamburg, Michigan, said a warning label might have made a difference in her case.

She started taking Ozempic off-label for weight loss in late June. Although this application of the medication has become somewhat common, Novo Nordisk, the drug’s maker, has said it does not promote or encourage it and leaves such decisions to doctors’ discretion.

By July 4, Stainer said, she began to feel unusually downtrodden.

“I was starting to have some pretty low feelings —  not suicidal, but just very low, just thinking about all the crap that I’ve gone through this last year,” she said.

Stainer said that although she attempted suicide when she was younger, the endocrinologist who prescribed her Ozempic did not ask about that aspect of her health history.

In early July, she said, she shared concerns about her mental health — along with physical symptoms like exhaustion — with an urgent care clinician, who sent her to the hospital. She was briefly put on psychiatric hold and stopped taking Ozempic.

Had she continued taking the medication, Stainer said, it’s possible her mental state would have become worse.

“Without a shadow of a doubt, I think I would have been at the cusp of, ‘Do I end my life here?’” she said.

Although Stainer said a doctor suggested Ozempic may have been the cause of her mental health challenge, it was not listed as such on her medical discharge paperwork. Determining causality in such cases is difficult. 

Anecdotes like Stainer’s have created a conundrum for regulators in the U.S. and abroad: Though some patients have described severe psychological reactions to GLP-1 receptor agonists, doctors aren’t noticing a trend and clinical trials don’t suggest that these side effects are correlated with the drugs.

That leaves lingering questions about what type of warning, if any, is warranted for patients taking Ozempic or Wegovy.

Doctors say this side effect is exceedingly rare, if it’s associated at all

Within two weeks of starting Wegovy in January, Teresa Bruce, a 53-year-old recruiter in Appleton, Wisconsin, said she felt “full-on depressed.”

“It started slowly and then all of a sudden, it was ‘wham!’ I was feeling suicidal,” she said. “I’m thinking about driving my car off a cliff or something.”

Bruce said she had shared her history of mild depression with the telehealth doctor who prescribed her Wegovy but was not told about any mental health side effects.

“I just had a gut feeling. I’m like, ‘I think this is the medication that’s doing this,’” she said, adding that she wasn’t feeling depressed before taking it.

A doctor’s note reviewed by NBC News attributed Bruce’s symptoms to Wegovy and said she should stop taking the drug.

But such experiences are quite rare, according to three medical experts interviewed for this article. None had seen any patients with experiences like that of Bruce or Stainer.

“As far as I’m aware, I have not seen it once in my patients,” said Dr. Eduardo Grunvald, an obesity medicine physician at UC San Diego Health.

As of March, the FDA’s adverse event reporting system, or FAERS, had received 57 reports of depression, suicidal ideation or suicide attempts related to Ozempic, and five related to Wegovy. By comparison, U.S. providers were writing around 60,000 new weekly prescriptions for Ozempic as of April, according to data from Novo Nordisk.

Chanapa Tantibanchachai, a press officer at the FDA, said the agency can’t verify that the reported events are directly caused by the medications.

“There has been no evidence of an increased risk of suicidal ideation, behaviors, or death due to suicide in any of the clinical programs,” she said.

Novo Nordisk said in a statement that it “remains confident in the benefit risk profile of the products.”

The drugmaker added that it takes all reports of adverse events seriously and is “continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals.”

Concerns about suicidal thoughts with other weight loss drugs

The reason weight loss drugs in the U.S. carry a warning about suicidal thoughts is that clinical trials of comparable medications, including Saxenda, Qsymia and Contrave, showed some evidence of this side effect in both the placebo groups and those who took the medications, according to Tantibanchachai.

But Tom Wadden, a psychology professor at the University of Pennsylvania’s Perelman School of Medicine, said he is not concerned that semaglutide could cause similar issues.

“I don’t think there’s a strong signal from this medication or class of medications that it’s associated with suicidal ideation, or with depression,” said Wadden, who sits on the scientific advisory board at Novo Nordisk and helped oversee a handful of Wegovy trials.

In the clinical trials, he added, “We did find that a couple of our patients reported suicidal ideation, but it seemed to be related to life events occurring.”

However, Grunvald pointed out that semaglutide trials excluded patients with history of suicidal behavior, so “they may be underestimating the risk.”

Still, the trials showed far lower rates of suicidal thoughts or behaviors than reported in the overall U.S. population, he said. Whereas around 4.3% of the adult population in the U.S. has had suicidal thoughts during the preceding year, only about 0.1% to 0.2% of trial participants did, Grunvald said.

Dr. Susanne Miedlich, an associate professor of medicine at the University of Rochester Medical Center, said more research is needed to determine how patients with a history of depression or suicidal ideation tolerate semaglutide — and if people with diabetes respond differently than those taking the medication for weight loss.

“If you give the same drug to a different population, you could, theoretically at least, have different outcomes,” she said.

Grunvald, meanwhile, suggested that other variables could factor in as well.

“There are some reports of suicidal ideation coming out of people who’ve had bariatric surgery, which raises the question: If there is a causation, is it from the therapy or does significant, massive weight loss cause any problems there?” he said.

If you or someone you know is in crisis, call 988 to reach the Suicide and Crisis Lifeline. You can also call the network, previously known as the National Suicide Prevention Lifeline, at 800-273-8255, text HOME to 741741 or visit SpeakingOfSuicide.com/resources for additional resources.