Some people are having hallucinations and other psychotic symptoms after stopping GLP-1 drugs

A case report published this week in The Primary Care Companion for CNS Disorders describes two patients who experienced acute psychotic and manic episodes within weeks of discontinuing tirzepatide, a dual GLP-1 and GIP receptor agonist prescribed for type 2 diabetes and obesity. The first patient, a 61-year-old man with a history of depression, stopped the medication in August 2025 because of nausea; by October he was admitted with auditory and visual hallucinations, paranoia, and a Cotard delusion — the fixed belief that he was dead. Extensive neurological workups, including MRI and lumbar puncture, were unremarkable. His symptoms resolved on antipsychotics, yet he was readmitted weeks later with catatonic depression requiring electroconvulsive therapy. The second patient, a 52-year-old man with anxiety, abruptly quit tirzepatide in September 2025 after losing 100 pounds in six months and increasing his marijuana use. He presented with classic mania: hyperverbal speech, grandiosity, and impulsivity. A low vitamin B12 level and chronic lacunar infarcts were noted but deemed unrelated to the acute picture; he was started on risperidone and transferred for psychiatric care.

Both cases share a striking temporal link: symptom onset followed rapid discontinuation rather than gradual taper. The authors, led by Corey Horien, MD, PhD, note that GLP-1 receptors are distributed throughout brain regions that regulate dopamine, reward, and mood, and that agonist withdrawal could unmask a dopaminergic surge or neuroinflammatory shift. That hypothesis aligns with emerging data showing GLP-1 agonists modulate dopaminergic firing and neuroinflammation in animal models, though human mechanistic studies remain sparse.

Meanwhile, a new Everyday Health survey of 501 adults with type 2 diabetes found that 30 percent of GLP-1 users stopped because of side effects, and 27 percent cited severe side effects as the primary reason. Anxiety or mood changes were reported by 26 percent of current users and 25 percent of past users — a signal that psychiatric symptoms are already common during treatment, not just after stopping. Women and Black, Indigenous, and People of Color respondents reported significantly higher rates of mood-related side effects than white men, raising questions about whether discontinuation risks differ across populations.

No formal tapering guidelines exist for GLP-1 agonists, and the FDA labels do not warn of withdrawal psychosis. Clinicians are left to extrapolate from case reports and pharmacology. The Horien team urges prospective monitoring of mood and cognition during and after discontinuation, especially in patients with prior psychiatric history. Until controlled data arrive, the safest course may be slow dose reduction with psychiatric follow-up — a practice already standard for other centrally acting drugs but not yet codified for this blockbuster class.