From the Guidelines
A psychosis workup should begin with a comprehensive clinical assessment, including a detailed history, mental status examination, and physical examination to identify potential causes, as recommended by the American Psychiatric Association 1. The initial assessment should include the reason for presentation, patient goals and preferences, psychiatric symptoms and trauma history, substance use, psychiatric treatment history, physical health assessment, psychosocial and cultural factors, mental status examination, and risk assessment for suicide and aggressive behaviors. Laboratory tests should include:
- Complete blood count
- Comprehensive metabolic panel
- Thyroid function tests
- Urinalysis
- Urine drug screen
- B12/folate levels Additional testing may include:
- HIV
- Syphilis serology
- Heavy metal screening if clinically indicated Brain imaging with CT or MRI is recommended to rule out structural abnormalities, as suggested by the American College of Radiology 1. An electroencephalogram (EEG) may be useful if seizure disorders are suspected. Lumbar puncture should be considered if CNS infection or autoimmune encephalitis is suspected. Psychological testing can help differentiate between primary psychotic disorders and other conditions. The workup should also include assessment of suicide risk and potential for violence. This systematic approach is essential because psychosis can result from primary psychiatric disorders (schizophrenia, bipolar disorder), substance use, medications, metabolic disturbances, neurological conditions, or infections, and early identification of the underlying cause is crucial for appropriate treatment, as management strategies differ significantly depending on etiology 1.
From the Research
Psychosis Workup
The workup for psychosis involves a comprehensive assessment to determine the underlying cause of the symptoms.
- The initial evaluation should include a thorough history, physical examination, and laboratory tests to rule out secondary causes of psychosis 2, 3, 4.
- The physical examination should include complete neurologic and mental status assessments, and vital signs should be monitored for any abnormalities 2.
- Laboratory tests may include a complete blood count, metabolic profile, thyroid function tests, urine toxicology, and measurement of parathyroid hormone, calcium, vitamin B12, folate, and niacin 2.
- Imaging studies, such as brain imaging, may be performed if there are atypical clinical features or "red flags" that suggest an underlying organic disease 5.
- A tiered approach to the workup of first-episode psychosis has been proposed, which includes a thoughtful consideration of the differential diagnoses and is followed and supported by laboratory, encephalographic, and imaging studies where appropriate 3.
Differential Diagnoses
The differential diagnoses for psychosis include primary psychiatric disorders, such as schizophrenia, and secondary causes, such as medical conditions or substance use 2, 6.
- Primary psychiatric disorders are likely to have auditory hallucinations, prominent cognitive disorders, and complicated delusions 2.
- Secondary causes of psychosis may include medical conditions, such as infections, inflammatory or autoimmune pathologies, and metabolic disorders, as well as substance use or medication side effects 2, 5.
- Delirium and dementia are two important disorders to rule out in the evaluation of psychosis 6.
Warning Signs of Secondary Psychosis
Warning signs of secondary psychosis include atypical clinical features, such as visual hallucinations, cognitive changes, and abnormal vital signs 2, 5.
- A subacute onset of psychosis should raise suspicion for an oncologic cause 2.
- Recent head injury or trauma, seizures, cerebrovascular disease, or new or worsening headaches should be investigated as potential causes of psychosis 2.
- Illicit drug use is a common medical cause of acute psychosis, and urine toxicology should be performed to rule out substance use 2.