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First Episode Psychosis Workup

Key considerations: Anti-NMDA receptor encephalitis, Substance-induced psychosis, CNS infection/tumor

Cannot miss

  • Anti-NMDA receptor encephalitis
  • Substance-induced psychosis
  • CNS infection/tumor
  • Thyroid disease
  • Temporal lobe epilepsy

Likely diagnoses

  • Primary psychotic disorder (schizophrenia spectrum)
  • Substance-induced psychosis
  • Mood disorder with psychotic features
  • Medical/neurological cause of psychosis

Red flags

  • Age >40 at first episode (medical cause more likely)
  • Rapid onset over days (vs weeks-months for primary psychiatric)
  • Fever or focal neurological findings
  • Visual hallucinations (auditory more typical of primary psychosis)
  • Known substance use

Workup

  • history: Timeline of symptom onset, substance use (including cannabis and synthetics), family psychiatric history, medical history; exam: Complete neurologic exam, mental status exam, signs of autoimmune disease, thyroid exam; labs: CBC, BMP, LFTs, TFTs, B12, folate, RPR, HIV, urine drug screen, urine pregnancy test; Anti-NMDA receptor antibodies if encephalitis suspected; imaging: Head CT then MRI brain; EEG if seizure suspected; bedside: Mental status exam, safety assessment

Management

  • immediate: Treat underlying medical cause if found; Safety assessment and 1:1 observation if danger to self or others; general: If primary psychosis: low-dose antipsychotic (risperidone 1-2mg or olanzapine 5mg); Early psychosis intervention programs; Family education; Avoid high-dose antipsychotics in first episode — more sensitive to side effects

Disposition

  • admit: Danger to self or others, unable to care for self, medical cause requiring workup; discharge: Stable and safe with outpatient early psychosis program and reliable follow-up; consults: Psychiatry, neurology if CNS cause suspected, rheumatology if autoimmune

Clinical pearls

  • Anti-NMDA receptor encephalitis is the great mimicker — young women with new psychiatric symptoms, movement disorder, and autonomic instability need LP and antibody testing
  • Complete medical workup is MANDATORY before applying a psychiatric diagnosis to first-episode psychosis
  • Visual hallucinations suggest organic/medical cause; auditory hallucinations are more typical of primary psychotic disorders

Source and review

  • APA Schizophrenia Treatment Guidelines 2020. Last reviewed: 2024-11-01