Schizophrenia, Emergency Medicine

Basics

Description

A chronic psychotic disorder characterized by delusions, hallucinations, disorganization, negative symptoms, and cognitive deficits:
- Premorbid phase:
  - Development of negative symptoms with deterioration of personal, social, and intellectual functioning
- Active phase:
  - Development of active delusions, hallucinations, and bizarre behavior
  - May be precipitated by a stressful event
- Residual phase:
  - Patients are left with impaired social and cognitive abilities
  - Psychotic symptoms may persist
- Subtypes: Catatonic, disorganized, paranoid, residual, undifferentiated
Onset typically early in adulthood (age <30)
Comorbid substance abuse (alcohol, cannabis, tobacco, and stimulants) is common
Violence may result from impaired judgment, paranoia, and command hallucinations
Life expectancy 12 " 25 yr less than general population likely because:
- 41% of patients have metabolic syndrome with increased risk of death due to cardiovascular events
- 5 " 10% of patients commit suicide
- Patients have decreased access to medical care
Disorganized thinking, abnormal behavior, and delusions may obscure the detection of medical illness
Medication noncompliance is a key reason for psychiatric decompensation and presentation to the ED

Etiology

Pathophysiology unclear but dopamine pathway strongly implicated
Genetic component (concordance rate of 50% in monozygotic twins)
Specific genes uncertain:
- Higher risk in patients with DiGeorge syndrome (22q11.2 deletion)
Perinatal risk factors:
- Influenza during 2nd trimester
- Maternal and postnatal infections
- Advanced paternal age
Use of cannabis may unmask psychosis in predisposed individuals

Diagnosis

Signs and Symptoms

Criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) require the presence of at least 2 of the following symptoms for more than 6 mo:

Delusions (fixed, false beliefs):
- Bizarre, paranoid, or grandiose
- Often persecutory, religious, or somatic content
Hallucinations:
- Commonly auditory or visual but may involve any sensory modality
Thought disorder:
- Disorganized speech ranging from odd, idiosyncratic logic to incoherence
Grossly disorganized or catatonic behavior
Negative symptoms:
- Apathy and amotivation
- Flat affect
- Social isolation
- Anhedonia

Essential Workup

Complete general and neurologic exam including vital signs and mental status exam
Screen for psychosis:
- Delusions:
  - "Do you feel anyone is trying to harm you or that you are being followed? "
  - "Is anyone trying to send you messages, steal, control, or block your thinking? "
- Hallucinations:
  - "Do you ever see or hear things that other people cannot see or hear? "
  - "Do you ever hear voices telling you to do things such as to harm yourself or others? "
Evaluate potential dangerousness to self or others:
- Screen for past violence or self-injury
- Content of psychotic symptoms should be explored to assess safety
Patient history and medication compliance may be unreliable. Obtain collateral history from additional sources:
- Friends and family
- Treaters (PCP, therapist, psychiatrist)
- Pharmacy
Evaluate for affective psychosis (bipolar, major depression, or schizoaffective disorder)
Evaluate for delirium or dementia
- Schizophrenia does not affect orientation.
Assess for drug-induced psychosis (see "Psychosis, Acute " )
Psychosis due to medical etiology should be ruled out

Diagnosis Tests & Interpretation

Lab

Toxicology screen
Electrolytes, BUN, creatinine, glucose, calcium
CBC with differential
TSH
Urinalysis

Imaging
Consider head imaging for new onset psychosis of undetermined etiology or new onset neurologic symptoms
Diagnostic Procedures/Surgery
EKG to monitor QT

Differential Diagnosis

Delirium
Drug-induced psychosis
Psychosis secondary to general medical conditions such as TLE, MS, LBD
Bipolar disorder
Major depression with psychotic features
Schizoaffective disorder:
- Schizophrenia with prominent depressive and/or manic symptoms during psychosis
Delusional disorder
Schizotypal personality
Brief psychotic episode:
- Similar symptoms, duration of <1 mo
Schizophreniform disorder:
- Similar symptoms, duration between 1 and 6 mo

Treatment

Pre-Hospital

Patients can display unpredictable and violent behavior toward themselves and others
Patients may require police presence and/or restraints to maintain safety
Local laws vary as they apply to involuntary restraint

Initial Stabilization/Therapy

Safety of healthcare workers and patient is paramount; security presence may be required
Behavioral interventions should be 1st line:
- Provide a calm, containing environment
- Potentially dangerous items should be removed from the patients room
- Use a reassuring voice and calm demeanor to set boundaries and verbally redirect the patient
If safety is a concern, patient needs to be under constant observation and physical or chemical restraints may be necessary
Acute agitation may be treated with haloperidol PO/IV/IM which can be augmented with lorazepam PO/IV/IM:
- Encourage voluntary PO meds prior to IM administration
- Other IM antipsychotics include olanzapine, chlorpromazine (monitor orthostatics), ziprasidone (monitor QT), and aripiprazole
- IM olanzapine should not be combined with IV benzodiazepines as this increases risk of cardiopulmonary collapse

Ed Treatment/Procedures

Psychiatric consultation in cases of decompensated schizophrenia
Antipsychotic medications are the mainstay of treatment
High-potency typical antipsychotic agents:
- Associated with less QT prolongation
- Higher propensity for extrapyramidal symptoms:
  - Dystonia
  - Parkinsonism
  - Akathisia
  - Tardive dyskinesia
- IV haloperidol associated with fewer extrapyramidal symptoms than PO/IM
Low-potency typical antipsychotics:
- Higher risk of QT prolongation
- Fewer extrapyramidal symptoms
- More sedating
- Orthostatic hypotension (must monitor)
- Anticholinergic side effects
- Lower seizure threshold
Atypical antipsychotic agents:
- Better tolerated with less EPS
- Associated with metabolic syndrome and weight gain
- Can cause orthostatic hypotension
- Nearly all antipsychotics increase QT:
  - More likely (ziprasidone)
  - Less likely (aripiprazole)
- Clozapine is the only antipsychotic that is clearly more effective for reducing psychotic symptoms and suicide risk:
  - Requires close monitoring of WBCs due to agranulocytosis
  - Highly sedating, hypotensive, lowers seizure threshold
  - Can cause QT prolongation
Long-acting antipsychotic preparations (given q2 " 6wk) include:
- Fluphenazine decanoate
- Haloperidol decanoate
- Olanzapine depot (Relprevv)
- Paliperidone palmitate (Sustenna)
- Risperidone microspheres (Consta)
If a high-potency conventional antipsychotic agent is initiated, patients younger than age 40 can be started on benztropine (Cogentin) 2 mg BID for 10 days to reduce the risk of dystonic reactions

Medication

Typical antipsychotics (1st generation):
- High potency:
  - Haloperidol 0.5 " 100 mg/d. Acute agitation 2.5 " 10 mg PO/IV/IM. Repeat q20 " 60min as needed
  - Fluphenazine 10 mg/d
  - Thiothixene 1 " 30 mg/d
- Medium potency:
  - Perphenazine 2 " 24 mg/d
  - Trifluroperazine 1 " 20 mg/d
- Low potency:
  - Chlorpromazine 0 " 200 mg/d in 3 div. doses
  - Loxapine 5 " 100 mg/d
  - Thioridazine 50 " 800 mg/d in 2 " 3 div. doses
Atypical antipsychotics (2nd generation):
- Aripiprazole 5 " 30 mg/d
- Asenapine 5 " 20 mg/d (SL)
- Clozapine 12.5 " 900 mg/d
- Iloperidone 1 " 24 mg/d
- Lurasidone 20 " 160 mg/d
- Olanzapine 5 " 20 mg/d
- Paliperidone 6 " 12 mg/d
- Quetiapine 25 " 800 mg/d
- Risperidone 1 " 16 mg/d
- Ziprasidone 20 " 160 mg/d
Benzodiazepines:
- Lorazepam (Ativan) 0.5 " 2 mg per dose augments antipsychotic for acute agitation

Black box warning: Elderly patients with dementia-related psychoses treated with antipsychotic drugs are at increased risk of death.

Follow-Up

Disposition

Admission Criteria

Admit to inpatient psychiatric hospital, if patient is medically stable and:
- Is a danger to self or others
- Is gravely disabled and unable to care for himself due to psychosis
- Has new-onset psychosis and medical etiology has been ruled out
Prior to transfer to psychiatric facility, patient must have acute medical and surgical issues addressed
Criteria for involuntary psychiatric hospitalization vary by state

Discharge Criteria

Patient is not a danger to self or others and is able to perform activities of daily living
Psychiatric follow-up is arranged
Psychotic symptoms may persist at time of discharge

Follow-Up Recommendations

Outpatient psychopharmacologic follow-up should occur within 1 wk of discharge
Patients taking antipsychotics (especially atypicals) should be monitored for QT prolongation and for obesity and related metabolic syndromes
Adjunctive cognitive behavioral therapy and other psychosocial treatments can help patients manage psychotic symptoms and improve medication compliance
Discuss smoking cessation and referral:
- 50 " 80% of patients with schizophrenia smoke tobacco

Pearls and Pitfalls

Visual, olfactory, gustatory, or tactile hallucinations should prompt medical workup for secondary causes of psychosis, as should atypical age of onset (>30 yr old)
Early treatment with antipsychotic medications and social interventions have consistently been associated with better outcomes in schizophrenia
Avoid using IM olanzapine with IV benzodiazepines as this increases risk for cardiopulmonary collapse
Patients who recently started antipsychotics who present with fever, rigidity, autonomic instability, and mental status changes should be assessed for neuroleptic malignant syndrome

Additional Reading

American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Text Revision (DMS-IV-TR), American Psychiatric Association, Washington, DC; 2000.
Buckley P, Citrome L, Nichita C, et al. Psychopharmacology of aggression in schizophrenia. Schizophr Bull. 2011;37:930 " 936.
Freudenreich O, Holt DJ, Cather C, et al. The evaluation and management of patients with first-episode schizophrenia: A selective, clinical review of diagnosis, treatment, and prognosis. Harv Rev Psychiatry. 2007;15:189 " 211.
van Os J, Kapur S. Schizophrenia. Lancet. 2009;374:635 " 645.

Codes

ICD9

295.10 Disorganized type schizophrenia, unspecified
295.20 Catatonic type schizophrenia, unspecified state
295.90 Unspecified schizophrenia, unspecified state
295.30 Paranoid type schizophrenia, unspecified
295.60 Schizophrenic disorders, residual type, unspecified

ICD10

F20.1 Disorganized schizophrenia
F20.2 Catatonic schizophrenia
F20.9 Schizophrenia, unspecified
F20.0 Paranoid schizophrenia
F20.3 Undifferentiated schizophrenia
F20.5 Residual schizophrenia

SNOMED

58214004 Schizophrenia (disorder)
191542003 Catatonic schizophrenia (disorder)
35252006 Disorganized schizophrenia (disorder)
64905009 Paranoid schizophrenia (disorder)
111484002 Undifferentiated schizophrenia (disorder)
26025008 Residual schizophrenia (disorder)
83746006 Chronic schizophrenia (disorder)

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