Some individuals have reported experiencing hallucinations and other psychotic symptoms following the discontinuation of GLP-1 medications, commonly used for weight loss and diabetes management. Research into the psychiatric effects of stopping these drugs is still in its early stages.
Two case reports published in The Primary Care Companion for CNS Disorders highlight the experiences of two men who developed significant psychiatric issues after ceasing GLP-1 treatment. One 61-year-old man stopped taking tirzepatide (Mounjaro, Zepbound) due to nausea. Two months later, he was hospitalized with paranoia, auditory and visual hallucinations, and Cotard’s delusion, a condition where a person believes they are dead or do not exist. These symptoms met the criteria for a psychotic disorder. Despite a history of depression, his condition worsened significantly after stopping the medication. Tests ruled out other neurological causes, and he was treated with antidepressants and antipsychotics. His symptoms initially improved but later recurred, leading to readmission for depression with catatonic features and eventual electroconvulsive therapy.
The second case involved a 52-year-old patient who also stopped tirzepatide abruptly after losing 100 pounds. Within a month, he was hospitalized for erratic behavior and mood swings, exhibiting symptoms of a manic episode including rapid speech, impulsivity, irritability, and grandiosity. While he had a history of anxiety, his post-discontinuation behavior was markedly different. His test results were normal aside from a low vitamin B12 level. He received antipsychotic medication and was transferred to a psychiatric facility.
GLP-1 medications are known to affect the brain, including areas involved in mood and reward processing. Research from the University of Virginia suggests these drugs can influence neurotransmitters and brain circuits related to the reward system activated by eating high-calorie foods. Psychotherapists note that these medications can impact mood by affecting neurotransmitters.
The authors of the case studies suggest that sudden psychiatric or mood symptoms after discontinuing GLP-1s may be an underrecognized phenomenon. They propose potential mechanisms such as inflammation in the central nervous system or impacts on dopamine production, particularly in patients with a predisposition to mental health issues. Both patients in the reports had prior histories of depression and anxiety, respectively. The researchers emphasize the importance of clinicians being aware of these potential side effects when patients stop taking GLP-1 treatments.