What medical conditions can cause psychosis?

Medical Causes of Psychosis

Secondary medical causes must be systematically excluded before diagnosing primary psychiatric psychosis, particularly in patients ≥65 years, those without prior psychiatric history, or presenting with atypical features such as visual hallucinations, altered consciousness, or abnormal vital signs. 1, 2

Critical First Step: Rule Out Delirium

Delirium is the most common cause of psychotic symptoms in elderly patients and missing this diagnosis doubles mortality. 3

• Delirium presents with fluctuating consciousness, acute onset over hours-to-days, inattention, and disorientation 1, 3
• Primary psychosis maintains intact awareness and level of consciousness 1, 2
• Visual hallucinations with altered consciousness strongly suggest delirium rather than primary psychosis 2
• Hypoactive delirium is especially common in older adults and carries higher mortality than hyperactive forms 2

Major Categories of Medical Causes

Infectious Causes

• Urinary tract infections and pneumonia are the most common infectious precipitants 2
• Central nervous system infections (encephalitis, meningitis) typically present with fever and altered mental status 1, 3
• HIV-related syndromes can manifest with psychotic symptoms 1, 4
• Systemic infections with sepsis can precipitate delirium with psychotic features 3

Neurological Disorders

• Seizure disorders, including nonconvulsive status epilepticus and postictal states 1, 3
• CNS lesions (brain tumors, congenital malformations, head trauma) 1, 5
• Stroke or cerebrovascular disease, particularly in elderly patients 3, 6
• Neurodegenerative disorders (Alzheimer's disease, Huntington's disease, Parkinson's disease, diffuse Lewy body disease, frontotemporal degenerations) 1, 7, 8
• Traumatic brain injury 3, 9
• Autoimmune encephalitis and inflammatory disorders 2, 3, 5

Metabolic and Endocrine Disorders

• Thyroid dysfunction (hyperthyroidism or hypothyroidism) 4, 2, 6
• Electrolyte abnormalities 2, 6
• Wilson's disease (particularly in younger patients with movement disorders) 1, 4
• Metabolic disorders including endocrinopathies 1
• Porphyria 6
• Parathyroid hormone abnormalities and calcium disorders 6

Substance-Related Causes

• Illicit drug use is the most common medical cause of acute psychosis 4, 6
• Intoxication from amphetamines, cocaine, hallucinogens, phencyclidine, alcohol, marijuana, cannabis, methamphetamine, and solvents 1, 9, 6
• Withdrawal states (particularly alcohol withdrawal requiring immediate benzodiazepine treatment to prevent seizures) 2, 3
• Medication-induced psychosis from stimulants, corticosteroids, anticholinergic agents 1, 4, 9
• Heavy metal toxicity 1

Autoimmune and Neoplastic Causes

• Autoimmune diseases 1, 2
• Neoplasms and paraneoplastic processes 1, 2
• Brain tumors (oligodendroglioma, glioblastoma, meningioma) can present with primarily psychiatric symptoms 3
• Subacute onset of psychosis should raise suspicion for oncologic causes 6

Nutritional Deficiencies

• Vitamin B12 deficiency 1, 6
• Folate deficiency 6
• Niacin deficiency 6

Other Medical Conditions

• Genetic or metabolic disorders 1
• Developmental disorders such as velocardiofacial syndrome 1
• Lipid storage disorders 1

Essential Diagnostic Workup

Mandatory Laboratory Tests

• Complete blood count to evaluate for anemia or infection 4
• Comprehensive metabolic panel including electrolytes, renal function, glucose, liver function 4
• Thyroid function tests (TSH, free T4) 4, 6
• Urinalysis to screen for urinary tract infections 4
• Urine toxicology screen given that illicit drugs are the most common medical cause 4, 6
• Vitamin B12, folate, and niacin levels 6
• Parathyroid hormone and calcium 6

Additional Testing Based on Clinical Context

• HIV testing if risk factors present 1, 4, 6
• Syphilis testing 6
• Ceruloplasmin and 24-hour urine copper if Wilson's disease suspected 4
• Cardiac enzymes if cardiac injury suspected 4
• Chromosomal analysis for patients with features suggestive of developmental syndromes 1
• Electroencephalogram for suspected seizure activity 1

Neuroimaging Indications

• Brain MRI is recommended to exclude structural lesions and assess for cerebral atrophy patterns 2, 3
• Neuroimaging is indicated for focal neurological deficits, head trauma history, atypical features, new-onset psychosis in elderly patients, or first-episode psychosis with neurological signs 3
• Consider C9orf72 genetic testing in late-onset presentations with family history of neurodegeneration 2

Clinical Red Flags Suggesting Medical Etiology

• Abnormal vital signs (fever, tachycardia, severe hypertension) 4, 6
• Altered level of consciousness or cognitive changes 4, 2
• Abnormal neurological examination 4
• Visual hallucinations (more common in medical causes than primary psychosis) 2, 6
• Acute onset over hours-to-days rather than gradual onset 3
• Age ≥65 years without prior psychiatric history 2
• Recent head trauma or new/worsening headaches 6

High-Risk Populations Requiring Extensive Workup

• Elderly patients presenting with new-onset psychosis 4, 2
• Patients without prior psychiatric history 4, 2
• Patients with substance abuse history (up to 50% of adolescents with schizophrenia have comorbid substance abuse) 1, 4
• Patients with preexisting or new medical complaints 4
• Lower socioeconomic populations 4

Critical Pitfalls to Avoid

• Missing delirium doubles mortality—always evaluate for fluctuating consciousness first 2, 3
• Overlooking withdrawal states that require immediate benzodiazepine treatment 2, 3
• Up to 46% of patients with psychiatric symptoms may have medical illnesses directly causing or exacerbating their presentation 4
• Up to 63% of patients with new psychiatric complaints may have a medical reason for their behavior 4
• Do not order extensive routine laboratory batteries in alert, cooperative patients with normal vital signs and noncontributory history/physical examination—this is costly and low-yield 4
• If psychotic symptoms persist longer than one week despite documented detoxification, consider primary psychotic disorder rather than substance-induced psychosis 1, 2