Late-life psychotic disorders

Definition and burden. Psychosis is the presence of delusions and/or hallucinations with loss of contact with reality. There is an increased incidence of psychotic symptoms in older adults compared with younger adults; the lifetime risk of psychosis is about 23%, and roughly 15% of older adults experience psychotic phenomena.

The single most important rule. Approximately 60% of new-onset psychosis in late life is secondary — due to a medical, neurological or drug cause. Primary psychosis is a diagnosis of exclusion. Older adults presenting with psychotic symptoms for the first time need a thorough evaluation before any psychiatric label is applied.

Classification — the "six D's" of late-life psychosis. Delirium · Disease (medical/neurological — hypothyroidism, B12 deficiency, hyponatraemia, cancer, temporal lobe lesions, epilepsy) · Drugs (levodopa and dopamine agonists, steroids, anticholinergics, alcohol/substance use and withdrawal) · Dementia (Alzheimer's, and especially DLB and Parkinson's disease dementia) · Depression (psychotic depression with nihilistic/guilt delusions) · Delusional disorder and late-onset schizophrenia.

Clinical clues that point to the cause. Fluctuating attention and altered consciousness → delirium. Recurrent, well-formed complex visual hallucinations of people, children or animals with parkinsonism, fluctuating cognition and REM sleep behaviour disorder → DLB, where misidentification delusions are the commonest type and severe neuroleptic sensitivity may occur. Nihilistic and guilt delusions with mood disturbance → psychotic depression. Well-systematised non-bizarre persecutory delusions with preserved function → delusional disorder. Purely visual hallucinations with intact insight in visual loss → Charles Bonnet syndrome (not psychosis, needs no antipsychotic).

Evaluation. History plus informant history; full drug and alcohol review; cognitive testing (MMSE/MoCA); audiometry and vision assessment. Investigations: CBC, sodium and potassium (mEq/L), calcium (mg/dL), glucose (mg/dL), renal and liver function, TSH, vitamin B12, VDRL/HIV, urine culture, ECG, and CT or MRI brain. If the workup is negative, refer to a psychiatrist to diagnose late-onset schizophrenia or delusional disorder.

Management principles. Treat the cause first — stop or reduce the offending drug, correct the metabolic abnormality, treat the infection, treat the depression. Environmental and psychosocial interventions are first-line — correct sensory deficits with hearing aids and cataract surgery, reduce isolation, simplify the environment, and educate carers. Antipsychotics are used judiciously, as needed: atypical agents at one-quarter to one-third of adult doses, with quetiapine or clozapine preferred in DLB and Parkinson's disease, and pimavanserin for Parkinson's disease psychosis. Note the boxed warning of increased stroke and mortality in dementia-related psychosis.

Xanomeline–trospium (KarXT), 2024–25. The first muscarinic M1/M4 receptor agonist antipsychotic, FDA-approved in September 2024 for schizophrenia. Because it is non-dopaminergic it causes no extrapyramidal symptoms, no prolactin elevation and no weight gain — the 2025 International Psychogeriatrics overview of late-onset psychoses identifies it as the most promising emerging therapy for late-life psychosis, with trials in dementia-related psychosis ongoing. APPROACH TO NEW-ONSET PSYCHOSIS IN AN OLDER ADULT New delusions and/or hallucinations after age 60 | Is attention/consciousness fluctuating? -- YES --> DELIRIUM: find & treat cause | NO Drug review (levodopa, steroids, anticholinergics, alcohol) -- positive --> withdraw/reduce | Metabolic + infective screen; B12, TSH, Na, Ca; neuroimaging -- positive --> treat DISEASE | Cognitive testing + informant history -- impaired --> DEMENTIA (AD / DLB / PDD) | Mood assessment -- depressed --> PSYCHOTIC DEPRESSION (antidepressant + antipsychotic or ECT) | Workup negative --> refer psychiatry: DELUSIONAL DISORDER or LATE-ONSET SCHIZOPHRENIA