First-episode psychosis refers to the first time a patient experiences psychotic symptoms, such as hallucinations or delusions. The differential diagnosis for first-episode psychosis is broad and includes both psychiatric and non-psychiatric etiologies. Psychiatric causes include primary psychotic disorders like schizophrenia and mood disorders like bipolar disorder with psychotic features. Non-psychiatric causes include substance-induced psychosis and psychosis due to medical conditions.
In a cohort of children and adolescents hospitalized for the medical workup of first-episode psychosis, 98.5% were diagnosed with a primary psychiatric condition and 1.5% with a medical etiology, specifically autoimmune encephalitis and medication-induced psychosis. Although a given patient with first-episode psychosis is far more likely to be found with a psychiatric condition, the consequences of overlooking a treatable underlying medical condition, such as these, can be devastating.
Experts agree that the evaluation of first-episode psychosis should include an extensive history and physical examination, but there is currently no consensus on further medical workup. While testing for all possible non-psychiatric etiologies is impractical and cost-ineffective, a 2020 review of the literature recommends the following for all patients with first-episode psychosis:
- Complete blood count (CBC) with differential to rule out delirium, infection, anemia, and to establish a baseline if starting a medication
- Urinalysis (UA) to rule out delirium and infection
- HIV test to rule out HIV infection
- Antitreponemal IgG to rule out neurosyphilis
- Comprehensive metabolic panel (CMP) to rule out delirium, Addison’s disease, hyperparathyroidism, hyper/hypoglycemia, and to obtain baseline sodium (Na) and liver function tests (LFTs)
- Thyroid-stimulating hormone (TSH) to rule out hyper/hypothyroidism, subacute thyroiditis, and Hashimoto’s disease
- Antinuclear antibody (ANA) test to rule out systemic lupus erythematosus
- Ceruloplasmin to rule out Wilson disease
- Toxicology screening to rule out drug intoxication, drug withdrawal, and substance-induced psychosis
- 25-OH Vitamin D to rule out vitamin D deficiency
- Folate to rule out folate deficiency
- Methylmalonic acid/B12 to rule out B12 deficiency and pernicious anemia
- Electroencephalogram (EEG) to rule out seizures, temporal lobe epilepsy, and interictal psychosis of epilepsy
- Hemoglobin A1C, fasting lipids, pregnancy test, and electrocardiogram for baseline measurements and monitoring if antipsychotics are started
Additional testing is recommended if clinically indicated, such as genetic testing and/or MRI if the patient is very young (i.e., less than 13 years old) or exhibits neurodegenerative symptoms or developmental delay.
It is worth noting that recommendations regarding neuroimaging in first-episode psychosis are mixed. While the aforementioned review recommends against routine neuroimaging, a more recent 2023 systematic review and meta-analysis supports its use as part of the initial assessment for all patients presenting with first-episode psychosis. The findings suggest that approximately 6% of patients had an abnormality that required a change in clinical management. The number needed to assess to detect such an abnormality was 18.
Ultimately, the medical workup for first-episode psychosis will require clinical judgment to balance the potential benefits of detecting and treating a rare but possible medical cause of psychosis against the costs of over-testing or delaying psychiatric treatment. If there are any questions about such a medical workup, providers are welcome to contact the SmartCare Behavioral Health Consultation Services (BHCS) provider psychiatric triage line at (858) 880-6405.
AUTHOR:
Dr. Kristen Kim, MD
Child, Adolescent and Adult Psychiatrist
Vista Hill Foundation