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15th February 2025
Medical causes of psychosis
It is important to rule out medical causes of psychosis before diagnosing it as a psychiatric condition, as these likely need different, time-sensitive management. A CT or MRI head is generally recommended in the first episodes of psychosis.
Factors suggesting a medical cause of psychosis include:
- Acute onset
- Onset at >40 years
- Non-auditory hallucinations (e.g. visual, olfactory, tactile)
- No family history of psychosis and no premorbid or prodromal symptoms
Key medical causes are summarised in Table 5.
Table 5 Key medical causes of psychosis and associated clinical features and investigations
| Condition | Clinical features | Investigations |
|---|---|---|
| Delirium | Cognitive decline, behavioural change, reversed night-day sleep-wake cycle and altered consciousness. Acute onset with fluctuating course. Common medications implicated in delirium include anticholinergic drugs, benzodiazepines, antihistamines, dihydropyridine calcium channel blockers, diuretics, and opioids. | Determine underlying cause, including pain, infection, nutrition, constipation, hydration, medication, environment (‘PINCH ME’). First line: haloperidol. |
| Structural brain problems, e.g. tumour, stroke | Symptoms depend on the territory affected.
E.g. peduncular hallucinosis, a relatively rare neurological disorder that causes vivid visual hallucinations following damage to the midbrain. There may be Lilliputian hallucinations featuring smaller-than-life people or animals. |
Neuroimaging. |
| Epilepsy | Ictal psychosis: associated with non-convulsive status epilepticus. Postictal: develops following a lucid phase, up to 7 days following cessation of a seizure; associated with temporal lobe epilepsy and generalised tonic-clonic seizures. Interictal: not related to the timing of seizures; typically associated with partial epilepsy; may indicate the presence of small brain tumours.Psychosis may also be caused by seizure medications. |
Clinical history of two seizures is needed for a diagnosis of epilepsy. EEG may help confirm the diagnosis.
Insomnia is usually the first sign of postictal psychosis, so preventative antipsychotic treatment may be started. |
| Neurodegenerative, e.g. dementia, Parkinson’s, CJD | Progressive cognitive decline, memory loss, functional difficulties, language deficit, personality changes. Can cause anxiety/depression and psychosis.
With Parkinson’s: tremor, rigidity, bradykinesia, postural instability, hyposomnia, sleep disorders. With CJD: muscle weakness, involuntary movements, poor co-ordination, peripheral neuropathy, visual disturbance. |
Neuroimaging and neurocognitive testing. More specialised tests if prion disease is suspected. |
| Demyelinating disease, e.g. MS | Fatigue, visual disturbance, peripheral neuropathy, muscle spasms, mobility problems. Associated with psychosis, some MS medications also induce/exacerbate psychosis. | Neuroimaging, evoked potential test, LP. |
| Inflammatory, paraneoplastic or infectious CNS disease | Fever and rapid progression. Encephalitis: flu-like symptoms may progress to seizures, weakness/paralysis and cognitive deficits. HSV commonest cause. | Neuroimaging and LP or rheumatology investigations if indicated. |
| Wilson disease | Liver and kidney disease and, more rarely, cardiomyopathy. Kayser-Fleischer rings. Neuropsychiatric symptoms include Parkinsonian features, dystonia, cognitive disorders (frontal lobe disorders and subcortical dementia) and psychosis. | Caeruloplasmin (low), 24 h urine copper (high), serum copper (low, except in acute liver failure). |
| Acute porphyria (cutaneous porphyrias do not affect CNS) | Abdominal pain, chest pain, peripheral neuropathy, nausea, bowel changes, red or brown urine, hypertension, tachycardia, seizures and cognitive defects. | Urine porphyrin precursor porphobilinogen (PBG). Genetic testing. |
| Lead poisoning | Tremor, headache, abdominal pain, bowel changes, muscle pain/weakness, memory problems, fatigue, cognitive defects and delirium. Burton’s line: blue tinge around the gums. Acute lead poisoning may progress to encephalopathy, seizure and death. | Heavy metal screen. Blood film may show basophilic stippling, microcytosis and hypochromia. |
| Vision loss | May trigger visual hallucinations, often with insight (Charles Bonnet syndrome). | Ophthalmology investigations. |
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