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Pathophysiology

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Table Graphic Jump Location
Table 42-1 Proposed Models for Schizophrenia
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Diagnosis & Evaluation

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  • Characteristic symptoms: >2 persisting ≥1mo: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms (affective flattening, alogia, or avolition); only 1 characteristic symptom required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on person's behavior or thoughts, or 2 or more voices conversing with each other
  • Social/occupational dysfunction: for a significant portion of time since onset of disturbance, 1 or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below level achieved prior to onset (or when onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement)
  • Duration: continuous signs of the disturbance persist for at least 6mo
  • Suggest psychiatry consult to rule out diagnosis of schizoaffective disorder, mood disorder, use of illicit substances, general medical conditions

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Treatment & Follow-Up

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  • 3 goals for treatment planning: (1) reduce or eliminate symptoms, (2) maximize quality of life & adaptive functioning, & (3) promote & maintain recovery from debilitating effects of illness to maximum extent possible

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Pharmacological Treatment

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  • Antipsychotics Agents
    • 1st generation (typical antipsychotics): chlorpromazine, fluphenazine, haloperidol, loxapine, molindone, perphenazine, thiothixene, thioridazine, trifluoperazine; MOA: ↑ D2 antagonism
      • Warnings: cerebrovascular events, neuroleptic malignant syndrome (see Chapter 44), tardive dyskinesia; Black Box Warning → elderly patients with dementia-related psychosis at ↑ risk of death with antipsychotic drugs (Can Med Assoc J 2007;176:627)
      • Monitor ECG, plasma prolactin levels, extrapyramidal side effects (EPS), abnormal involuntary movement scale (AIMS)
    • 2nd generation (atypical antipsychotics): asenapine, aripiprazole, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone
      • MOA: ↑ 5-HT2A antagonism & ↓ to moderate D2 antagonism (exception: aripiprazole—partial agonist at D2 & 5-HT1A; 5-HT2A antagonism)
      • Warnings: cerebrovascular events (Drug Saf 2010;33:273), hyperglycemia, hyperlipidemia, neuroleptic malignant syndrome, QTc prolongation (Drugs Aging 2009;26:997), tardive dyskinesia; Black Box Warning → elderly patients with dementia-related psychosis treated with antipsychotic drugs are at ↑ risk of death
      • Monitor ECG, fasting blood glucose, CBC, BP, LFTs, BMI, waist/hip ratio, waist circumference, diabetic risk screening; additional monitoring → quetiapine—thyroid function tests; olanzapine & risperidone—plasma prolactin ...

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