Best Dx/Best Rx: Schizophrenia

Schizophrenia

William T. Carpenter, Jr., M.D.
Gunvant K. Thaker, M.D. University of Maryland School of Medicine

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

Chronic psychotic symptoms, especially hallucinations and delusions, appearing in late adolescence or early adulthood
Disorganization of thought and behavior
Diminished emotional experience and expression, low drive, reduced speech in some patients
Subtle impairments in cognition, often appearing early in life
Deficit schizophrenia
- Negative symptoms and psychosis
- 15%-20% of all schizophrenia cases
- Occurs predominantly in males
Nondeficit schizophrenia: negative symptoms are absent

Differential Diagnosis

Schizotypal personality disorder
Affective disorders with psychosis
Delusional disorders
Depression
Mania
Substance abuse
- Alcohol
- Psychotomimetic drugs
- Analgesics
- Antibiotics
- Anticholinergics
- Cardiovascular drugs
- Dopamine agonists
- Endocrine drugs
- H₂ receptor antagonists
- Stimulants and sympathomimetics
Medical conditions
- Cancer (e.g., CNS neoplasm, hyperviscosity syndromes, paraneoplastic syndromes)
- Cardiovascular (e.g., anoxia, encephalopathy)
- Infections and sequelae (e.g., encephalopathy, Lyme disease, neurosyphilis)
- Metabolic, endocrine (e.g., porphyria, Addison disease, Cushing disease, hepatic encephalopathy, hypoglycemia, hypocalcemia/hypercalcemia, hypothyroidism/hyperthyroidism)
- Neurologic (e.g., Alzheimer disease, complex partial seizures, Huntington disease, multiple sclerosis, stroke, Wilson disease)
- Nutritional deficiencies (e.g., folic acid, niacin, vitamin B₁₂)
- Lupus cerebritis

Best Tests

DSM-IV Criteria

At least two of the following symptoms for significant period during 1 mo:
- Delusions
- Hallucinations
- Disorganized speech
- Grossly disorganized behavior
- Negative symptoms (e.g., lack of emotion and social drive and engagement)
Deterioration in social/occupational functioning in one or more of the following areas:
- Work
- Interpersonal relationships
- Self-care
Continuous signs of the disturbance for 6 mo, including ≥ 1 mo of positive symptoms
Exclusion of schizoaffective and mood disorders
Exclusion of substance-induced or medical disorder
In pervasive developmental disorders, presence of delusions or hallucinations for ≥ 1 mo

Physical Examination

Rule out psychosis caused by physical ailments
Identify evidence of self-mutilation
Essential to guide drug treatment
- Patients with motor abnormalities: select a drug with low potential for causing extrapyramidal symptoms or tardive dyskinesia
- Patients with obesity: avoid drugs that increase weight

Laboratory Tests

Toxicology screens
- Provide alternative explanation for psychosis
- Confirm comorbid substance abuse
Lipid profiles
- Identify risk of hyperlipidemia (associated with some antipsychotic drugs)
- Identify risk of diabetes
ECG: provides baseline for patients who take drugs that can prolong QT interval
- EEG: may exclude temporal lobe epilepsy
- MRI of brain: rule out other causes of psychosis

Best Therapy

Acute Treatment

Antipsychotic medication
Hospitalization, depending on patient safety and cooperation

Maintenance Therapy

Neuroleptics

Can produce neurologic side effects
Chlorpromazine
- Dose: initially, 50-100 mg/day, up to 500 mg/day in two divided doses
- Cost/mo: ~ $20
Fluphenazine
- Dose
  - Initially, 2.5-5 mg/day in two or three divided doses, up to 20 mg/day
  - Decanoate formulation can be given I.M. every 3 wk
- Cost/mo: ~ $25
Haloperidol
- Dose
  - Initially, 1-5 mg q.d. or b.i.d., titrated upward according to clinical response
  - Long-lasting I.M. formulation is available
- Cost/mo: ~ $20
Loxapine
- Dose: initially, 10 mg/day in two divided doses, up to about 60 mg/day
- Cost/mo: ~ $25
Mesoridazine
- Dose: initially, 50 mg/day, up to 300-400 mg/day in two divided doses
- Cost/mo: ~ $25
Molindone
- Dose: initially, 50 mg/day, up to 200 mg/day in two divided doses
- Cost/mo: ~ $30
Perphenazine
- Dose: initially, 4 mg/day, up to 32-40 mg/day in two to four divided doses
- Cost/mo: ~ $25
Pimozide
- Dose: initially, 2 mg/day, up to 12 mg/day
- Cost/mo: ~ $130
Thioridazine
- Dose: initially, 50 mg/day in two divided doses, up to 400 mg/day
- Cost/mo: ~ $20
Thiothixene
- Dose: 5-10 mg/day in two divided doses, up to 30-40 mg/day
- Cost/mo: ~ $25

Atypical Antipsychotics

General characteristics
- No more effective than neuroleptics for reducing positive psychotic symptoms, but fewer side effects
- Reduced incidence of dystonia and tardive dyskinesia
- Some are associated with weight gain, hyperlipidemia, new-onset type 2 diabetes
Clozapine
- Monitor for agranulocytosis
- Superior efficacy
- Dose: Initially, 25-50 mg/day in two divided doses, up to 600-800 mg/day
- Cost/mo: ~ $155
Aripiprazole
- Less likely to cause motor side effects than the other neuroleptics
- Dose: initially 10-15 mg q.d., up to 30 mg/day
- Cost/mo: ~ $250
Olanzapine
- Dose: initially, 5-10 mg/day in two divided doses, up to 30 mg/day
- Cost/mo: ~ $300
Quetiapine
- Dose: 50 mg/day in two divided doses, up to 600 mg/day
- Cost/mo: ~ $300
Risperidone
- Dose
  - Initially, 2 mg q.d. or b.i.d., titrated upward according to clinical response up to 16 mg/day
  - Higher doses associated with motor side effects
  - Long-lasting I.M. formulation available
- Cost/mo: ~ $250
Ziprasidone
- Dose: initially, 20 mg b.i.d., titrated up to 80 mg b.i.d.
- Cost/mo: ~ $250

Antianxiety Drugs

Reduce anxiety in schizophrenic patients

Drugs for Depression and Mania

Those used in affective disorders can be useful for these symptoms in schizophrenia

Drugs for Aggression

Aggression caused by psychosis: antipsychotic drugs
Aggression caused by akathisia as a side effect of antipsychotic drugs: change in drug or addition of another drug, such as an anticholinergic
Beta blockers
Atypical antipsychotic drugs

Electroconvulsive Therapy

Particularly effective for catatonic stupor, excitement, and acute psychotic conditions
Positive symptoms are reduced, but long-term functional impairments are not reversed
Limitations
- Not widely available
- Litigation and societal attitudes restrict its use
- Therapeutic gains not easily maintained
- Little evidence of effectiveness in patients who are resistant to antipsychotic drugs

Psychosocial Interventions

Intensive psychotherapy less effective than drug treatment
Supportive psychosocial treatment with drug treatment
Cognitive-behavioral therapy for treatment-resistant positive psychotic symptoms
Family therapy and education programs for patients and their families
Social and living skills training
Supported employment programs
Supervised residential living arrangements
Crisis-management services as alternatives to hospitalization during symptom exacerbation

Best References

El-Sayeh HG, et al: Cochrane Database Syst Rev CD004578, 2006 PMID 16625607

Kirkpatrick B, et al: Arch Gen Psychiatry 58:165, 2001 PMID 11177118

Lieberman JA, et al: N Engl J Med 353:1209, 2005 [PMID 16172203]

William T. Carpenter, Jr., M.D., has served on the scientific advisory board of Janssen, L.P.; Ortho-McNeil Neurologics, Inc.; Merck & Co., Inc.; and Solvay Wyeth Pharmaceuticals.

Gunvant K. Thaker, M.D., has no commercial relationships with manufacturers of products or providers of services discussed in this module.

December 2006