Schizophrenia

SOURCE

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.

CONDITION/DISORDER SYNONYMS

• Psychosis.

DEFINITION

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

ETIOLOGY

• Unknown, but evidence suggests genetic basis.

PATHOPHYSIOLOGY

• 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.

EPIDEMIOLOGY

• 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.

CLINICAL PRESENTATION

SIGNS AND SYMPTOMS

• 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.

DIAGNOSIS

• 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)

DIFFERENTIAL DIAGNOSIS

• Other psychoses (eg, delusional disorders, atypical psychoses)

• Manic episodes.

• Obsessive-compulsive disorder.

• Psychotic depression.

• Drug intoxication and abuse.

• Thyroid, adrenal, and pituitary disorders.

DESIRED OUTCOMES

• Alleviate target symptoms.

• Avoid medication side effects.

• Improve psychosocial functioning and productivity.

• Achieve patient adherence with prescribed regimen.

• Involve patient in treatment planning.

TREATMENT: GENERAL APPROACH

• 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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