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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Requires >=2 active symptoms for >=1 month with continuous signs for >=6 months
- One symptom must be delusions, hallucinations, or disorganized speech
- Functional decline and exclusion of mood/substance/medical causes are required
- Antipsychotics are first-line
- Clozapine for treatment resistance or persistent suicidality; requires ANC monitoring
Overview
Schizophrenia involves positive symptoms, negative symptoms, disorganization, and cognitive impairment. DSM-5-TR requires characteristic symptoms, dysfunction, and duration of at least 6 months including prodromal or residual periods. Mood episodes, if present, are brief relative to total illness duration.
Epidemiology
Prevalence is about 1%. Onset is late adolescence to early 30s, earlier in men. Risks include family history, prenatal/perinatal complications, cannabis use in vulnerable people, urbanicity, migration, and childhood adversity. Mortality is increased from suicide, cardiometabolic disease, smoking, and substance use.
Clinical Features
Symptoms
Auditory hallucinations, often voices commenting or conversing
Persecutory, referential, grandiose, somatic, or bizarre delusions
Disorganized speech or behavior
Negative symptoms: flat affect, avolition, alogia, social withdrawal
Command hallucinations, catatonia, severe agitation, or inability to care for self
Signs
Responding to internal stimuli, thought blocking, poor grooming
Blunted affect, social withdrawal, disorganized behavior
Fever, autonomic instability, fluctuating consciousness, or focal neurologic signs suggest medical cause
EPS, tardive dyskinesia, metabolic syndrome from treatment
Investigations
First-line
DSM-5-TR assessmentSymptoms, duration >=6 months, functional decline, exclusion of mood/substance/medical causes
Safety/capacity assessmentSuicide, violence, command hallucinations, grave disability, ability to eat/drink
First-episode workupCBC, CMP, TSH, B12/folate, HIV/syphilis when indicated, pregnancy test, urine toxicology
Second-line
Baseline antipsychotic monitoringWeight/BMI, BP, glucose/A1c, lipids, AIMS, prolactin symptoms, ECG if QT risk
Brain imagingFocal signs, trauma, seizures, atypical onset, delirium, mass concern
DifferentialSubstance psychosis, bipolar/MDD with psychosis, schizoaffective disorder, delirium, dementia
Specialist
Coordinated specialty careFirst-episode psychosis benefits from early multidisciplinary intervention
Clozapine monitoringANC, myocarditis, seizures, constipation/ileus, metabolic syndrome
1
Acute psychosis
- Hospitalize if danger, grave disability, severe disorganization, catatonia, or inability to maintain safety
- Start antipsychotic after considering medical/substance causes; IM antipsychotic +/- benzodiazepine if severe agitation
- Catatonia: lorazepam and/or ECT; avoid reflexive antipsychotic escalation when NMS/malignant catatonia possible
2
Maintenance treatment
- Second-generation antipsychotics are common; choose based on response and adverse effects
- First-generation antipsychotics are effective but have higher EPS risk
- Long-acting injectables help recurrent relapse due to nonadherence
3
Treatment resistance and psychosocial care
- Clozapine after failure of two adequate antipsychotic trials or persistent suicidality/aggression
- Coordinated care, family psychoeducation, CBT for psychosis, supported employment/education, substance treatment
- Treat smoking and cardiometabolic risk aggressively
Complications
- Suicide:
- Metabolic syndrome:
- EPS and tardive dyskinesia:
- Neuroleptic malignant syndrome:
- Substance use:
- Functional disability:
USMLE Step 2 CK Exam Tips
- 1>=6 months = schizophrenia; 1-6 months = schizophreniform; <1 month = brief psychotic disorder
- 2Psychosis only during mood episodes = mood disorder with psychotic features
- 3Psychosis >=2 weeks without mood symptoms + mood symptoms dominate = schizoaffective disorder
- 4Clozapine is for treatment resistance and lowers suicide risk
- 5Risperidone can cause hyperprolactinemia; olanzapine/clozapine cause metabolic syndrome
- 6Acute dystonia after haloperidol: benztropine or diphenhydramine
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