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• Psychosis


  Characterized by positive symptoms (e.g. delusions, disorganized speech, hallucinations, behavior disturbance, illusions), negative symptoms (e.g. alogia, avolition, flat affect, anhedonia, social isolation), and cognitive dysfunction (e.g. impaired attention, working memory, executive function)

  
• Schizophrenia


  A type of psychosis characterized by positive symptoms, negative symptoms, and cognitive dysfunction, leading to impaired psychosocial functioning

  
• Schizophrenia is characterized by positive symptoms, negative symptoms, and cognitive dysfunction

  
• Positive symptoms include delusions, disorganized speech, hallucinations, behavior disturbance, and illusions
• Negative symptoms include alogia, avolition, flat affect, anhedonia, and social isolation
• Cognitive dysfunction includes impaired attention, working memory, and executive function
• Schizophrenia causation theories


  • Genetic predisposition
  • Obstetric complications with hypoxia
  • Increased neuronal pruning
  • Neurodevelopmental disorders
  • Neurodegenerative theories
  • Dopamine receptor defect
  • Regional brain abnormalities including hyper- or hypoactivity of dopaminergic processes in specific brain regions
  • Increased ventricular size and decreased gray matter

  
• Alterations in glutamatergic neurotransmission are involved in the pathophysiology of schizophrenia
• Genes controlling N-methyl-D-aspartate (NMDA) receptor activity are involved in the pathophysiology of schizophrenia
• Immune/autoimmune disorders and abnormalities of autoantibodies and cytokine functioning are involved in the pathophysiology of schizophrenia
• Positive symptoms


  May be closely associated with dopamine receptor hyperactivity in the mesocaudate
• Negative and cognitive symptoms


  May be most closely related to dopamine receptor hypofunction in the prefrontal cortex
• Acute psychotic episodes in schizophrenia may involve being out of touch with reality

  
• After acute psychotic episodes, there are typically residual features in schizophrenia

  
• Comorbid psychiatric and medical disorders are common in schizophrenia

  
• Medication nonadherence is a common problem in schizophrenia
• The Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), specifies the diagnostic criteria for schizophrenia

  
• Criterion A for schizophrenia diagnosis in DSM-5 requires at least 2 of the following for a significant portion of time: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms, with at least one being delusions, hallucinations, or disorganized speech

  
• Criterion B for schizophrenia diagnosis in DSM-5 requires significantly impaired functioning

  
• Before treatment, a mental status examination, physical and neurologic examination, family and social history, psychiatric diagnostic interview, and laboratory workup should be performed for schizophrenia

  
• Laboratory workup for schizophrenia

  • Complete blood count
  • Electrolytes
  • Hepatic function
  • Renal function
  • Electrocardiogram
  • Fasting serum glucose
  • Serum lipids
  • Thyroid function
  • Urine drug screen
• Treatment goals for schizophrenia

  • Alleviate target symptoms
  • Avoid side effects
  • Improve psychosocial functioning and productivity
  • Achieve compliance with the prescribed regimen
  • Integrate the patient back into the community
  • Prevent relapse
  • Involve the patient in treatment planning
• Nonpharmacological treatments for schizophrenia include psychosocial rehabilitation and programs involving the family aimed at supportive employment and housing
• First-generation antipsychotics (FGAs)


  Have high dopamine D2 antagonism and low serotonin-2 receptor (5-HT2A) antagonism
• Second-generation antipsychotics (SGAs)


  Exhibit moderate-to-high D2 antagonism and high 5-HT2A antagonism
• Clozapine

  Shows low D2 antagonism and high 5-HT2A antagonism
• Antipsychotic selection is based on the need to avoid certain side effects, concurrent medical or psychiatric disorders, and patient or family history of response
• Clozapine has superior efficacy for suicidal behavior in schizophrenia
• Negative symptoms are generally less responsive to antipsychotic therapy
• Predictors of good antipsychotic response in schizophrenia include prior response to the drug, absence of alcohol or drug abuse, acute onset and short duration of illness, later age of onset, affective symptoms, family history of affective illness, medication adherence, employment, and good premorbid adjustment

  
• The initial therapy goals in the first 7 days of treatment are decreased agitation, hostility, anxiety, and aggression and normalization of sleep and eating
• During initial therapy, the antipsychotic dose is titrated to the minimum effective dose
• 1ST GEN (FGA)


  • not adherence
  • cause weight gain (as many as 25kg)
  • need ECG
• 2ND GEN (SGA)


  • long half-life - take time to see the effect
  • some need TDM
  • some interact with other med, food
• LAI

  • when pt not adhere to med
  • given by healthcare professional
  • expensive
  • long half-life - some can up to 3 months - pt not have to take daily injection
• Stages of Schizophrenia treatment

  1. Initial Therapy

  2. Stabilization Therapy

  3. Maintenance Therapy

  
• Initial Therapy


  1. The goals during the first 7 days of treatment are decreased agitation, hostility, anxiety, and aggression and normalization of sleep and eating

  2. Titrate the antipsychotic dose over the first few days to an average effective dose

  3. Rapid titration of dose is not recommended

  4. If there is no improvement within 2 weeks at a therapeutic dose, then move to the next treatment stage

  5. In partial responders who are tolerating the antipsychotic well, it may be reasonable to titrate above the usual dose range for 2–4 weeks with close monitoring
• Intramuscular (IM) antipsychotic administration


  • can be used to calm agitated patients
  • However, this approach does not improve the extent of response, time to remission, or length of hospitalization
• IM lorazepam 2 mg

  as needed for agitation added to the maintenance antipsychotic is a rational alternative to an injectable antipsychotic
• Combining IM lorazepam with olanzapine or clozapine is NOT recommended because of the risk of hypotension, central nervous system (CNS) depression, and respiratory depression