Blockbuster obesity drugs have transformed how we treat the condition – but doctors are warning they may cause potentially severe psychiatric effects.
Two new case reports reveal how two American patients became psychotic after taking semaglutide, the key ingredient in Ozempic and Wegovy.
One morbidly obese woman, 42, had been taking the drug for three weeks when she began suffering delusions that she was dead and attempted to strangle herself.
The symptoms went away after she came off the medication.
Another man, 72, who was described as ‘highly functional’, became manic after six weeks on the drug. He began cleaning the house compulsively and was convinced all his neighbors were dead.
Patients taking weight loss drugs such as semaglutide, the main ingredient in Wegovy and Ozempic, have reported behavior changes such as manic episodes as well as impulsive behavior leading to attempted suicides
The case reports were raised at a recent meeting of the American Psychiatric Association (APA).
A slew of reports just like these case have been reported around the world.
The doctors who treated the patients have called for patients given the new obesity drugs to be monitored once a week, even if they don’t have a history of mental health issues.
For patients who do, they want healthcare providers to do a thorough background and family history check to gauge their risk.
Zepbound and Wegovy include warnings on their labels about possible suicidal behavior, while Ozempic’s lacks any warnings about psychological effects.
None of their labels include warnings or contraindications for people with bipolar disorder, warning them that they could see worsened depression or manic episodes.
A new KFF poll found that one in eight American adults have used the new obesity drugs, meaning millions could be susceptible to potentially severe psychiatric issues.
Dr Shahan Syed, from Bergen New Bridge Medical Center in New Jersey, described how the 42-year-old woman had a history of PTSD and bipolar 1 disorder.
She also had morbid obesity, meaning her body mass index was above 40, and type 2 diabetes.
Because of her psychiatric history, she was deemed not a candidate for bariatric surgery and was started on Ozempic.
According to Dr Syed, the medication drove up her anxiety, which pushed her toward impulsive behavior such as attempting to take her own life.
Just three weeks in, the patient suddenly developed ‘behavioral disruptions’, including a feeling that she had died. She also attempted to self-strangulate, said Dr Syed.
He said: ‘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.’
Doctors generally do not know yet why semaglutide would cause mania and other behavior changes. Semaglutide works on receptors in the brain involved in appetite regulation.
Activation of these receptors can influence the activity of other neurotransmitters involved in mood, including serotonin and dopamine.
Altering levels of dopamine, which is associated with motivation, reward, and pleasure, can contribute to manic symptoms such as impulsivity, restlessness, high energy, and reduced inhibitions.
And serotonin plays an outsized role in mood regulation, so knocking levels of this neurotransmitter out of balance can lead to severe mood instability typical of manic episodes.
‘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.’
An evaluation by the FDA of Ozempic and similar drugs found no evidence they cause suicidal thoughts after conducting ‘detailed reviews‘.
Meanwhile, the 72-year-old man who was otherwise described as ‘highly functional’, and prescribed semaglutide for his type 2 diabetes.
He also had a history of depression, dementia-like symptoms following a neurological procedure, a benign tumor in his pituitary gland, and hypothyroidism.
About six weeks into his regimen, the man’s wife noticed stark behavior changes. He would suddenly swing from existential crisis to goal-directed activities, such as deep-cleaning the house at the drop of a hat.
He had been admitted to the hospital thinking he had encephalitis or inflammation in the brain ‘because it was so acute of a change,’ according to Dr Jodie Nghiem at Weill Cornell Medicine in New York City.
But blood tests came back normal, and because of the man’s advanced age – psychotic and bipolar disorders typically come on in early adulthood – psychiatrists ruled out mania and psychosis.
Still, doctors placed him on an antipsychotic, the main class of drugs used to treat schizophrenia and psychosis, and sometimes to treat bipolar disorder.
Around 18 percent of US adults, roughly 45 million people, are being treated for depression, which can worsen obesity and drive someone to seek out Wegovy, Ozempic, Zepbound, or its sister drug Mounjaro.
Dr Sayed, who has called for the addition of a warning for people with certain psychiatric conditions including bipolar disorder, said: ‘I would really like all healthcare providers — irrespective of psychiatry — neurology, endocrine, to do a thorough family history and psychiatric history.’
