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Source: Crismon ML, Argo TR, Buckley PF. Schizophrenia. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. http://accesspharmacy.com/content.aspx?aid=7987911. Accessed June 8, 2012.

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  • Psychosis

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  • Chronic heterogeneous syndrome of disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affect, cognitive deficits, and impaired psychosocial functioning.

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  • Unknown, but evidence suggests genetic basis.

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  • Psychosis may result from hyper- or hypoactivity of dopaminergic processes in specific brain regions.
  • Deficiency of glutamatergic activity produces symptoms similar to those of dopaminergic hyperactivity and possibly symptoms seen in schizophrenia.
  • Schizophrenic patients with abnormal brain scans have higher whole blood serotonin (5-hydroxytriptamine [5-HT]) concentrations that correlate with increased ventricular size.

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  • Prevalence ranges from 0.6–1.9% using strict diagnostic criteria.
  • Worldwide prevalence is similar among most cultures.
  • Onset usually in late adolescence or early adulthood; rarely occurs before adolescence or after age of 40 years.
  • Prevalence equal in males and females, but illness onset tends to be earlier in males.

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Signs and Symptoms

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  • Positive symptoms:
    • Delusions
    • Disorganized speech (association disturbance)
    • Hallucinations
    • Behavior disturbance (disorganized or catatonic)
    • Illusions
  • Negative symptoms:
    • Alogia (poverty of speech)
    • Avolition
    • Affective flattening
    • Anhedonia
    • Social isolation
  • Cognitive dysfunction:
    • Impaired attention
    • Working memory
    • Executive function
  • Residual features after resolution of acute episode:
    • Anxiety
    • Suspiciousness
    • Lack of volition
    • Lack of motivation
    • Poor insight
    • Impaired judgment
    • Social withdrawal
    • Difficulty in learning from experience
    • Poor self-care skills

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  • Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR) criteria:
    • Persistent dysfunction lasting longer than 6 months.
    • Two or more symptoms (present for at least 1 month), including:
      • Hallucinations
      • Delusions
      • Disorganized speech
      • Grossly disorganized or catatonic behavior
      • Negative symptoms
    • Significantly impaired functioning (work, interpersonal, or self-care).

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Differential Diagnosis

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  • Other psychoses (e.g., delusional disorders, atypical psychoses)
  • Manic episodes
  • Obsessive-compulsive disorder
  • Psychotic depression
  • Drug intoxication and abuse
  • Thyroid, adrenal, and pituitary disorders

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  • Alleviate target symptoms.
  • Avoid medication side effects.
  • Improve psychosocial functioning and productivity.
  • Achieve patient adherence with prescribed regimen.
  • Involve patient in treatment planning.

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  • Prior to starting treatment, perform:
    • Mental status examination
    • Physical and neurologic examination
    • Family and social history
    • Psychiatric diagnostic interview
    • Laboratory workup:
      • Complete blood count (CBC)
      • Electrolytes
      • Hepatic function
      • Renal function
      • Electrocardiogram (ECG)
      • Fasting serum glucose
      • Serum lipids
      • Thyroid function
      • Urine drug screen
  • First-line agents: second-generation antipsychotics (SGAs), except clozapine.
  • SGAs cause few extrapyramidal side effects and less effect on serum prolactin than first-generation antipsychotics (FGAs) but have increased risk for metabolic side effects, including:
    • Weight gain
    • Hyperlipidemia
    • Diabetes mellitus
  • Antipsychotic selection should be based on:
    • Need to avoid certain side effects
    • Concurrent medical or psychiatric disorders
    • Patient or family history of response
  • Negative symptoms generally less responsive to antipsychotic therapy than positive symptoms.
  • If partial or poor adherence, consider long-acting or depot injectable antipsychotic, for example:
    • Risperidone microspheres
    • Paliperidone palmitate
    • Extended-release olanzapine
    • Haloperidol decanoate
    • Fluphenazine decanoate

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  • Psychosocial rehabilitation programs
  • Cognitive behavioral therapy

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