What investigations are required in the first episode of psychosis?

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From the Guidelines

A comprehensive workup for a first episode of psychosis should include both physical and psychiatric evaluations to rule out organic causes and establish a diagnosis, as recommended by the American Psychiatric Association 1.

Initial Investigations

Initial investigations should include:

  • A complete blood count
  • Comprehensive metabolic panel (liver and kidney function tests)
  • Thyroid function tests
  • Vitamin B12 and folate levels
  • A urine drug screen These tests are essential to rule out underlying medical conditions that may be causing the psychotic symptoms, such as metabolic disorders, infections, or substance abuse 1.

Additional Tests

Additional tests should include:

  • Syphilis serology
  • HIV testing (with consent)
  • Inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate
  • Brain imaging with MRI to exclude structural abnormalities, though CT may be used if MRI is unavailable
  • An electroencephalogram (EEG) to rule out seizure disorders, particularly if the presentation includes fluctuating consciousness or unusual movements These tests can help identify potential underlying causes of psychosis, such as infections, autoimmune disorders, or neurological conditions 1.

Specialized Tests

Specialized tests, such as lumbar puncture, may be indicated if there are signs of infection or autoimmune encephalitis, with cerebrospinal fluid analysis for cells, protein, glucose, and potentially autoimmune antibodies 1. Genetic testing might be considered if there's a strong family history of psychosis.

Importance of Early Identification

Early identification of organic causes can prevent inappropriate antipsychotic treatment and address potentially reversible conditions, improving long-term outcomes for patients experiencing psychosis for the first time 1. Approximately 5-10% of first-episode psychosis cases have an underlying medical cause that requires specific treatment, highlighting the importance of a comprehensive workup.

From the Research

Investigations Required in First Episode of Psychosis

The following investigations are required in the first episode of psychosis:

  • A thorough history and examination to evaluate the patient with first episode psychosis (FEP) 2
  • Laboratory tests, including:
    • Complete blood count 3, 4
    • Metabolic profile 3, 4
    • Thyroid function tests 3, 4
    • Urine toxicology 3
    • Measurement of parathyroid hormone, calcium, vitamin B12, folate, and niacin 3
  • Imaging studies, such as encephalographic studies, where appropriate 2
  • Testing for human immunodeficiency virus infection and syphilis should also be considered 3
  • A broad screening to exclude secondary causes of schizophrenia, followed by exclusion of specific diseases informed by treatability and epidemiology, and medical baseline measures 4
  • A complete neurologic and mental status assessment to identify any cognitive changes, abnormal vital signs, or other symptoms that may indicate a medical cause of psychosis 3

Differential Diagnosis

The differential diagnosis of first episode psychosis should include a broad range of neurological, general medical, and psychiatric conditions 5, such as:

  • Psychotic-spectrum disorders
  • Non-psychotic disorders with similar symptoms
  • Medical conditions that can cause psychosis, such as illicit drug use, head injury or trauma, seizures, cerebrovascular disease, or new or worsening headaches 3
  • Oncologic causes, which should be suspected in cases of subacute onset of psychosis 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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