What is the cause of psychosis (psychotic disorder) onset?

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From the Guidelines

A psychosis workup should involve a comprehensive evaluation, starting with a thorough history and physical examination, including vital signs, neurological assessment, and mental status examination, as recommended by the most recent study 1. This approach is necessary to diagnose and determine the cause of psychotic symptoms, which can result from primary psychiatric disorders, substance use, medications, neurological conditions, metabolic disturbances, or infections.

Key Components of a Psychosis Workup

  • A thorough history and physical examination, including vital signs, neurological assessment, and mental status examination
  • Laboratory tests, including:
    • Complete blood count
    • Comprehensive metabolic panel
    • Thyroid function tests
    • Vitamin B12 and folate levels
    • Urinalysis
    • Urine drug screen
    • HIV testing
  • Additional tests, such as syphilis serology, heavy metal screening, and autoimmune panels, if clinically indicated
  • Brain imaging with CT or MRI, especially for first-episode psychosis or atypical presentations
  • Consideration of an EEG if seizure disorder is suspected
  • Psychological testing and a detailed psychiatric evaluation to assess thought content, perceptual disturbances, and cognitive function

Importance of Early Identification

Early identification of the underlying cause of psychosis allows for appropriate treatment, potentially improving outcomes and preventing further deterioration of mental status, as highlighted in the study 1. The economic impact of delirium, a related condition, is profound, with total costs estimated at $38 to $152 billion each year 1, emphasizing the need for prompt and effective management. By following a comprehensive approach to psychosis workup, healthcare providers can ensure that patients receive timely and appropriate treatment, ultimately improving morbidity, mortality, and quality of life outcomes.

From the Research

Definition and Causes of Psychosis

  • Psychosis is a symptom complex that may include hallucinations, delusions, disorders of thought, and disorganized speech or behavior 2
  • Acute psychosis can be primary, symptomatic of a psychiatric disorder, or secondary, caused by a specific medical condition 2
  • Medical causes of psychosis can include illicit drug use, head injury or trauma, seizures, cerebrovascular disease, and oncologic conditions 2, 3, 4

Evaluation and Diagnosis of Psychosis

  • A thorough history, examination, and workup are necessary to evaluate a patient with first-episode psychosis 3, 4
  • Laboratory tests, such as a complete blood count, metabolic profile, and thyroid function tests, can help identify underlying medical causes 2, 4
  • Imaging studies and encephalographic tests may also be necessary in some cases 3
  • A careful evaluation must be performed to differentiate psychotic symptoms caused by general medical conditions from psychosis caused by a primary psychiatric disorder 5

Medical Workup for Psychosis

  • There is no agreed-upon standard for the initial medical work-up of first-episode psychosis, but a comprehensive approach should include broad screening, exclusion of specific diseases, and medical baseline measures 4
  • The medical workup should consider the likelihood of disease, laboratory test performance, and relevance of positive test results 4
  • Clinicians should also consider testing for human immunodeficiency virus infection, syphilis, and other medical conditions that can cause psychosis 2, 6

Treatment and Management of Psychosis

  • Prompt recognition of the etiology of psychosis can improve treatment, consultation, and prognosis 2
  • Correction of reversible causes, sedation, and appropriate disposition are key to the successful management of patients with psychosis 5
  • Current research has focused on negative symptoms and cognitive impairment in psychotic illness, and new medications have been introduced to target these symptoms 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Psychosis.

Emergency medicine clinics of North America, 2000

Research

Psychosis.

Continuum (Minneapolis, Minn.), 2018

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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