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SOURCE

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Source: Crismon ML, Kattura RS, Buckley PF. Schizophrenia. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146064659.

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CONDITION/DISORDER SYNONYMS

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  • Psychosis.

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DEFINITION

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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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ETIOLOGY

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  • Unknown, but evidence suggests genetic basis.

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PATHOPHYSIOLOGY

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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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EPIDEMIOLOGY

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  • Lifetime prevalence ranges from 0.3% to 0.7%.

  • 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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CLINICAL PRESENTATION

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SIGNS AND SYMPTOMS
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  • Positive symptoms:

    • Suspiciousness.

    • Unusual thought content (delusions)

    • Hallucinations.

    • Conceptual disorganization.

  • Negative symptoms:

    • Alogia (poverty of speech)

    • Avolition.

    • Affective flattening.

    • Anhedonia.

  • Cognitive dysfunction:

    • Impaired attention.

    • Impaired working memory.

    • Impaired 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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DIAGNOSIS

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  • Diagnostic and Statistical Manual of Mental Disorders, 5th ed., (DSM-V-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 (eg, delusional disorders, atypical psychoses)

  • Manic episodes.

  • Obsessive-compulsive disorder.

  • Psychotic depression.

  • Drug intoxication and abuse.

  • Thyroid, adrenal, and pituitary disorders.

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DESIRED OUTCOMES

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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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TREATMENT: GENERAL APPROACH

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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:

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