Blockbuster obesity drugs have changed the way we treat the condition, but doctors warn they could cause potentially serious psychiatric effects.
Two new case reports reveal how two American patients became psychotic after taking semaglutide, the key ingredient in Ozempic and Wegovy.
A morbidly obese woman, 42, had been taking the drug for three weeks when she began suffering from delusions that she was dead and tried to strangle herself.
The symptoms disappeared after she stopped taking the medication.
Another man, 72, who was described as ‘highly functional’, became manic after six weeks of taking the drug. He began compulsively cleaning the house and was convinced that all his neighbors were dead.
Patients taking weight loss medications such as semaglutide, the main ingredient in Wegovy and Ozempic, have reported behavioral changes such as manic episodes and impulsive behavior leading to suicide attempts.
The case reports were discussed at a recent meeting of the American Psychiatric Association (APA).
There have been a slew of reports like these cases around the world.
The doctors treating the patients have called for patients receiving the new obesity drugs to be checked once a week, even if they have no history of mental health problems.
For patients who do, they want providers to do a thorough background and family history check to assess their risk.
Zepbound and Wegovy include warnings on their labels about possible suicidal behavior, while Ozempic contains no warnings about psychological effects.
None of their labels contain warnings or contraindications for people with bipolar disorder, warning them that they may experience worsened depression or manic episodes.
A new KFF survey found that one in eight American adults has taken the new obesity drugs, meaning millions could be susceptible to potentially serious psychiatric problems.
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 was also morbidly obese, meaning her body mass index was over 40, and type 2 diabetes.
Due to her psychiatric history, she was not considered a candidate for bariatric surgery and was started on Ozempic.
According to Dr. Syed, the medication increased her anxiety, causing her to exhibit impulsive behavior, such as attempting to commit suicide.
Just three weeks later, the patient suddenly developed “behavioral disturbances,” including the feeling that she had died. She also tried to strangle herself, Dr. Syed said.
He said: ‘I suspect we will unfortunately see many more cases like this, if only because prescribing these drugs is so common.’
Doctors generally don’t yet know why semaglutide would cause mania and other behavioral changes. Semaglutide acts 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 the levels of dopamine, which are associated with motivation, reward and pleasure, can contribute to manic symptoms such as impulsivity, restlessness, high energy and decreased inhibitions.
And serotonin plays a big role in regulating mood, so if the levels of this neurotransmitter become unbalanced, it can lead to severe mood instability typical of manic episodes.
‘It mainly works on the fat cells, but it also works on the muscles. And the brain is essentially all of that. Would this affect the brain? We do not know.’
An FDA review of Ozempic and similar drugs found no evidence that they cause suicidal thoughts after conducting “detailed reviews.”
Meanwhile, the 72-year-old man, otherwise described as “highly functional,” prescribed semaglutide for his type 2 diabetes.
He also had a history of depression, dementia-like symptoms after a neurological procedure, a benign tumor in his pituitary gland and hypothyroidism.
About six weeks after his treatment, the man’s wife noticed major behavioral changes. He suddenly switched from an existential crisis to goal-oriented activities, such as thoroughly cleaning the house in an instant.
He had been hospitalized because he thought he had encephalitis, or inflammation in the brain, “because there was such an acute change,” said Dr. Jodie Nghiem of Weill Cornell Medicine in New York City.
But the blood tests were normal, and because of the man’s old age — psychotic and bipolar disorders typically emerge in early adulthood — psychiatrists ruled out mania and psychosis.
Still, doctors placed him on an antipsychotic, the main class of medications used to treat schizophrenia and psychosis, and sometimes to treat bipolar disorder.
About 18 percent of American adults, roughly 45 million people, are being treated for depression, which can worsen obesity and prompt 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 – regardless of their psychiatry – to do neurology, endocrine, a thorough family history and psychiatric history .’