Some Patients Suffered Psychiatric Issues After Ozempic Initiation

NEW YORK CITY -- Some patients who newly started a GLP-1 receptor agonist quickly developed psychiatric symptoms, a few case reports detailed here.

One case involved a female, age 42, with a history of bipolar I disorder, post-traumatic stress disorder (PTSD), morbid obesity, and type 2 diabetes. Because of her psychiatric history, she was deemed not a candidate for bariatric surgery and was started on semaglutide (Ozempic).

Just 3 weeks into semaglutide treatment, the patient suddenly developed behavioral disruptions, protracted nihilistic delusion, and then attempted to self-strangulate, reported Shahan Syed, MD, of Bergen New Bridge Medical Center in Paramus, New Jersey, at the American Psychiatric Association (APA) annual meeting.

But after the patient stopped semaglutide, the suicidal ideation and behavior slowly reversed.

"I suspect that we're going to see much more of these sorts of cases, unfortunately, just because of how commonplace the prescribing is of these medications," Syed told MedPage Today. "Even those patients who are prescribed [GLP's] who may not have a [psychiatric] history should be evaluated once a week just to check in on their mood, their sleep, their appetite, and especially their anxiety."

"This is becoming such a popular medication and it has a lot of great effects," he continued. "It works on fat cells primarily, but it also works on muscles. And the brain is essentially all that. Would this be affecting the brain? We don't know."

A slew of reports just like this case have been reported, prompting the FDA and European Medicines Agency (EMA) to look into the link between GLP's and suicidality. But just last month, the EMA issued its final conclusion following a 9-month review of reports and data, clearing this popular class of agents of having a causal link with suicidal thoughts. The FDA is still currently reviewing the issue, but released its preliminary evaluation in January saying these drugs "likely" don't cause suicidality.

Agents in the GLP-1 agonist class include exenatide (Byetta, Bydureon BCise), liraglutide (Victoza), dulaglutide (Trulicity), lixisenatide (Adlyxin), semaglutide (Ozempic, Rybelsus, Wegovy), and tirzepatide (Mounjaro, Zepbound), a dual GIP/GLP-1 receptor agonist. These agents carry indications for treating type 2 diabetes, obesity, or both.

Though there isn't one currently, Syed said he thinks these agents should carry a boxed warning for bipolar disorder. He also said clinicians should prescribe these agents ultimately on a case-by-case basis.

"I would really like all healthcare providers -- irrespective of psychiatry -- neurology, endocrine, to do a thorough family history and psychiatric history," Syed advised.

"This particular patient escalated quickly and within 2 to 3 weeks she was having hypomanic-type symptoms: irritability, mood lability, sleep disturbances, she wasn't sleeping for about 2 to 3 days," he explained. "That resulted in [what] could be akathisia, could be restlessness, but subsequently anxiety is the biggest factor that tips us over the edge doing something impulsive, which this patient particularly did."

This wasn't the only case report from the meeting linking GLP's with psychiatric behaviors.

A male patient, age 72, who was previously described as "highly functional" was started on semaglutide for type 2 diabetes, explained Jodie Nghiem, MD/MBA candidate at Weill Cornell Medicine in New York City. In addition to diabetes, he also had a history significant for depression, normal pressure hydrocephalus status post ventriculoperitoneal shunt (VPS), prolactinoma on cabergoline, and hypothyroidism.

But 6 weeks into semaglutide treatment, his wife noticed a drastic change in his behavior -- described as manic. This involved a sudden swing towards goal-directed activities like cleaning house and an "almost nihilistic delusion" that neighbors were dead.

"[It was] just very different from his baseline activity," Nghiem told MedPage Today. "He was admitted for the thought of encephalitis because it was so acute of a change."

But his hospital work-up was notable for normal prolactin, thyroid hormone, with functioning VPS, and unremarkable autoimmune panel. A primary psychiatric disorder like psychosis or mania was also deemed unlikely because of the patient's age, though he was ultimately discharged from the hospital on an antipsychotic.

Nghiem echoed a similar sentiment as Syed, agreeing that as GLP-1 receptor agonists continue to grow in popularity, that healthcare providers across all specialties should be aware of potential adverse effects. Providers should also be aware of any patient-specific factors, like age in this case, that may make patients more vulnerable to adverse effects, she suggested.