Some GLP-1 Patients Suffer Psychosis After Stopping, Reports Say
Two case reports describe men who developed psychiatric symptoms, including hallucinations and mania, within weeks of stopping tirzepatide. The authors call it an underrecognized phenomenon and urge more research into how GLP-1 drugs affect the brain.
Two men developed serious psychiatric symptoms within weeks of stopping the weight loss drug tirzepatide, according to case reports published in the Primary Care Companion for CNS Disorders, adding to evidence that some GLP-1 patients suffer mental health effects after quitting.
Tirzepatide is sold as Mounjaro and Zepbound. Both men were hospitalized.
By the end of their first year on GLP-1 drugs, more than half of patients stop taking them. Reasons include high costs, unpleasant side effects and satisfaction with weight already lost. Weight is likely to return quickly once the drug stops.
Two patients, two presentations
A 61-year-old man stopped tirzepatide in August 2025 because of nausea. Two months later he was hospitalized with worsening confusion and erratic behavior.
Doctors recorded paranoia, auditory and visual hallucinations and Cotard's delusion, in which a person believes they are dead or do not exist. His symptoms met the criteria for a psychotic disorder. He had a history of depression, which worsened significantly in the month before admission.
Tests on his cerebrospinal fluid, brain MRIs and an electroencephalogram all came back normal, ruling out several other causes. Doctors told him to continue his antidepressant, Zoloft, and added two antipsychotics, Zyprexa and Haldol.
He improved enough to go home. Weeks later he was readmitted with depression with catatonic features, becoming motionless and unresponsive. He required inpatient care and was treated with electroconvulsive therapy.
The second patient, 52, stopped tirzepatide abruptly in September 2025 after losing 100 pounds over six months. A month later he was admitted for erratic behavior and mood swings.
He had a history of anxiety. His behavior after quitting met the criteria for a manic episode, with fast, continuous, incoherent speech, impulsivity, irritability and grandiosity. His test results were normal apart from a low vitamin B12 level. Doctors gave him the antipsychotic Risperdal and transferred him to a psychiatric facility.
What researchers suspect
GLP-1 drugs act on more than the digestive system. Research from the University of Virginia suggests they affect a brain circuit involved in processing emotions, including how the brain rewards high-calorie food with dopamine.
"These medications impact neurotransmitters, and so they can have an impact on mood," Amy Walters, a psychotherapist who works with people with metabolic disease, told the American Psychological Association.
The case authors say sudden mood or psychotic symptoms after stopping the drugs could be "an underrecognized clinical phenomenon." They call for more research into how GLP-1s affect the brain.
They suggest the drugs could cause inflammation in the central nervous system, affecting dopamine production and contributing to psychotic symptoms in at-risk patients. Both men had a history of mental health problems.
