First Episode Psychosis Workup
Before initiating treatment for first-episode psychosis, it is essential to consider and exclude physical illnesses that can cause psychosis through a structured medical evaluation 1.
Essential Diagnostic Components
Clinical Assessment
Assessment should be timely, depending on urgency, and flexible in terms of location 1. The evaluation must include:
- Comprehensive neurological examination - Nearly universal completion (97.1%) in real-world practice 2
- Mental status examination - To identify focal neurologic deficits, cognitive impairment, or atypical features that would warrant more extensive workup
- Risk assessment - Evaluate for self-harm, aggression, and need for inpatient versus outpatient management 1
- Family involvement - Families should be included in the assessment process, as they are usually in crisis and require emotional support 1
Laboratory Investigations
Blood analyses should be performed in all patients 2:
- Complete blood count
- Comprehensive metabolic panel
- Thyroid function tests
- Liver function tests
- Baseline metabolic parameters (particularly important before initiating antipsychotics)
Drug screening is essential - 82.4% completion rate in practice, with 44.6% testing positive for cannabis in one cohort 2. Urine toxicology identified substance-related findings in 8.1% of pediatric cases 3.
Neuroimaging: A Selective Approach
Neuroimaging should NOT be routine but rather clinically guided 4. This represents an important divergence from some older guidelines:
- The evidence is clear: While structural abnormalities are relatively common findings, they rarely require clinical intervention (median 3.5% across studies) and are very rarely the cause of psychotic symptoms (median 0%, range 0-3.3%) 4
MRI or CT should be performed when:
- Focal neurologic deficits are present
- Atypical clinical features exist
- Neurological abnormalities on examination
- Cognitive impairment beyond what is expected
- New-onset seizures
- Head trauma history
- Severe or unusual headache
In the absence of these red flags, routine neuroimaging is not supported by evidence 4. The ACR Appropriateness Criteria found the yield of CT in detecting pathology responsible for psychotic symptoms ranges from only 0% to 1.5% in patients without neurologic deficits 5. In pediatric populations, neuroimaging identified clinically explanatory findings in only 1.3% of cases, and all had neurological abnormalities or atypical features 3.
When Neuroimaging IS Indicated
If clinical features warrant imaging 5:
- First-line: Non-contrast head CT for acute presentations
- MRI is preferred when the clinical picture is unclear, presentation is atypical, or there are abnormal examination findings 5
- MRI has higher sensitivity for detecting small infarcts, encephalitis, subtle SAH, and specific pathologies (temporal lobe lesions, multiple sclerosis, encephalitis) 5
Optional/Selective Investigations
EEG - Performed in 38.2% of cases but did not identify psychosis etiology in any pediatric case without other neurological features 2, 3. Reserve for patients with:
- Suspected seizure disorder
- Altered consciousness
- Specific clinical indicators
Lumbar puncture - Rarely performed (5.9%) and should be reserved for suspected CNS infection or inflammatory conditions 2
Common Pitfalls to Avoid
Over-testing without clinical indication - The appropriate screening procedure is conventional history-taking, mental status, and neurological examination, not reflexive imaging 4
Delaying treatment while awaiting imaging - In patients without neurological signs, treatment should not be delayed for routine neuroimaging
Missing substance use - Drug screening is high-yield and should not be omitted
Ignoring baseline metabolic parameters - Essential before starting antipsychotics to monitor for metabolic syndrome
Failing to assess for specific treatable causes - Consider Wilson disease, systemic lupus erythematosus, Huntington disease in appropriate clinical contexts 5
Organic Etiology Considerations
Approximately 14% of first-episode psychosis cases have an organic or toxic etiology 6. However, the absence of well-established red flags means clinical judgment must guide the extent of workup rather than routine extensive testing 3.
Corticosteroid-induced psychosis should be considered in patients with recent steroid exposure 3.