Discontinuing Mounjaro and Zepbound Linked to Psychiatric Symptoms

Research has highlighted that stopping GLP-1 medications, specifically tirzepatide, commonly known as Mounjaro and Zepbound, can lead to severe psychiatric symptoms. Two case reports published in the "Primary Care Companion for CNS Disorders" indicate potential risks following abrupt discontinuation of these treatments.

Both cases involved men with pre-existing mental health conditions who developed acute psychiatric symptoms after halting their medication. The first individual, a 61-year-old man, ceased treatment in August 2025 due to nausea. Approximately two months later, he exhibited severe confusion and erratic behaviour, experiencing auditory and visual hallucinations alongside paranoia and Cotard's delusion, a rare psychiatric disorder where an individual believes they are dead or do not exist. Despite extensive medical evaluations, including brain imaging and tests of cerebrospinal fluid, no clear cause for his symptoms was identified. He was administered antipsychotic treatment and later required electroconvulsive therapy after a decline into severe depressive episodes.

The second patient, a 52-year-old man with a history of anxiety, stopped taking tirzepatide in September 2025 following a substantial weight loss of around 100 pounds (45 kg) over a six-month period. About a month later, he displayed significant mood disturbances, including irritability and rapid, disorganised speech. His symptoms were classified as a manic episode, leading to psychiatric care and treatment with antipsychotics.

The findings from these cases raise significant questions about the neurological effects of GLP-1 medications. The medications interact with GLP-1 receptors in the brain regions responsible for appetite control and mood regulation. It remains unclear if the psychiatric symptoms were directly linked to the discontinuation of tirzepatide. However, both patients had underlying health conditions that might have influenced their responses. For instance, the second patient also presented low vitamin B12 levels and increased marijuana usage prior to developing his symptoms.

While the reports suggest that stopping GLP-1 drugs could trigger severe psychiatric symptoms in vulnerable individuals, it is essential to note that this does not imply that these medications inherently cause psychosis or mania. According to a report from the U.S. Food and Drug Administration (FDA), a review of 91 clinical trials involving over 107,000 participants indicated no increased risk of suicidal thoughts or other psychiatric adverse events associated with GLP-1 medications compared to a placebo.

Healthcare professionals emphasise the importance of not discontinuing GLP-1 treatments without consulting a medical provider. Individuals may choose to stop due to side effects, financial concerns, or other issues, but any changes in treatment should be discussed with a healthcare professional. Patients experiencing new symptoms, such as confusion or significant mood changes, after stopping medication are advised to seek immediate medical attention. The authors of the case reports emphasized the need for further investigation into the psychiatric implications of discontinuing these medications, labelling the phenomenon as one that is often under-recognised clinically.