Schizophrenia

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Schizophrenia

  1. 1. Chapter 13
  2. 2. Schizophrenia- Readings <ul><li>Chapter 13 </li></ul><ul><li>Chapter 36 </li></ul><ul><ul><li>Sections </li></ul></ul><ul><ul><ul><li>36.18 pages 1043 to 1062 </li></ul></ul></ul><ul><ul><ul><li>36.30, pages 1091 to 1098 </li></ul></ul></ul>
  3. 3. What is Schizophrenia? <ul><li>Clinical syndrome of variable but profoundly disruptive psychopathology </li></ul><ul><li>It involves: </li></ul><ul><ul><li>Cognition, emotion, perception and other aspects of behavior </li></ul></ul><ul><li>Normally begins before age 25 </li></ul><ul><li>Persists throughout life </li></ul><ul><li>Affects persons of all social classes </li></ul>
  4. 4. Epidemiology <ul><li>Gender and Age </li></ul><ul><ul><li>Equal prevalence in men and women </li></ul></ul><ul><ul><li>1 in 100 persons will develop the condition during their lifetime, with peak ages 10 to 25 in men and 25 to 35 in women </li></ul></ul><ul><ul><li>Women can display bimodal age distribution with a second peak occurring in middle age </li></ul></ul><ul><ul><li>3% to 10% of women with schizophrenia present with disease onset after age 40 </li></ul></ul><ul><ul><li>About 90% of patients in treatment for schizophrenia are between 15 and 55 years of age </li></ul></ul>
  5. 5. Reproductive Factors <ul><li>Marriage among schizophrenics has led to an increased number of children born to both schizophrenic parents. </li></ul>
  6. 6. Medical Illness <ul><li>Patients with Schizophrenia have higher incidence of death from accidents and natural causes than the general population. </li></ul><ul><li>Studies have shown that up to 80% of patients with schizophrenia have significant concurrent medical illnesses, and up to 50% are undiagnosed. </li></ul>
  7. 7. Other Factors Related to the Development of Schizophrenia <ul><li>Patients with schizophrenia are more likely to have been born in winter and early spring and less likely to have been born in late spring and summer </li></ul><ul><li>Season specific risk-factors may influence the development of the condition </li></ul><ul><ul><li>Expossure to pathogens </li></ul></ul><ul><li>Prenatal malnutrition may play a role in schizophrenia </li></ul>
  8. 8. Substance Abuse <ul><li>Common in Schizophrenia </li></ul><ul><li>Lifetime prevalence often greater than 50% for any drug (other than tobacco) </li></ul><ul><li>Lifetime prevalence for alcohol abuse, 40% </li></ul><ul><li>Patients that reported high levels of cannabis use (more than 50 ocassions) were at sixfold increase risk of schizophrenia compared to non-users </li></ul><ul><li>Up to 90% of schizophrenic patients may be dependent on nicotine </li></ul>
  9. 9. Biochemical Basis: Dopamine Hypothesis <ul><li>Dopamine hyperactivity hypothesis </li></ul><ul><ul><li>Initially supported by neuroscientists and clinitians </li></ul></ul><ul><ul><li>Supported by observing drugs that enhance dopamine activity </li></ul></ul><ul><ul><ul><li>Amphetamines- in chronic amounts can induce symptoms virtually identical to those in paranoid psychosis </li></ul></ul></ul><ul><ul><ul><li>This hypothesis failed at explaining many other aspects of schizophrenia such as negative symptoms, cognitive deficits and other neurochemical and pathological findings </li></ul></ul></ul>
  10. 10. Biochemical Basis: Dopamine Hypothesis <ul><li>Antipsychotics neither cure or completely prevent relapse of symptoms </li></ul><ul><ul><li>30% of patients are refractory to treatment with antipsychotics </li></ul></ul><ul><ul><li>Conventional antipsychotics have a tendency to cause </li></ul></ul><ul><ul><ul><li>Extrapyramidal symptoms </li></ul></ul></ul><ul><ul><ul><li>Poor efficacy against negative symptoms </li></ul></ul></ul><ul><ul><ul><li>Inability to reverse or prevent cognitive impairment </li></ul></ul></ul><ul><ul><ul><li>Inability to permit a normal level of psychosexual and work function </li></ul></ul></ul><ul><ul><ul><li>Atypical antipsychotics which are less specific blockers of dopamine may be superior to Haldol and result in less extrapyramidal symptoms. </li></ul></ul></ul><ul><ul><ul><li>Pharmacotherapy of Schizophrenia; The Past, Presnt and Future. Current Drug Therapy, 2006, Vol1, No. 13 </li></ul></ul></ul>
  11. 11. Biochemical Basis:Serotonin Hypothesis <ul><li>Hyper-Serotonin hypothesis </li></ul><ul><ul><li>First observed in the 1950s when researchers noticed its similarity to LSD, which competes for 5-HT receptors resulting in psychosis-like symptoms </li></ul></ul><ul><ul><li>Evidence for action of 5HT lies in observations of brain behavior, neurotransmitter systems, drug mechanisms and postmortem studies. </li></ul></ul><ul><ul><li>Some studies found elevated levels of 5-HT in blood platelets </li></ul></ul><ul><ul><li>By far the strongest evidence of the role of 5-HT is the mechanism of atypical antipsychotic drugs like clozapine </li></ul></ul>
  12. 12. Pharmacotherapy <ul><li>Modern treatment primarily relies on somatic drug therapy </li></ul><ul><li>Most drugs used to treat schizophrenia antagonize post synaptic dopamine receptors </li></ul><ul><li>Antipsychotics are (Atypical)the mainstay of pharmacotherapy of schizophrenia </li></ul><ul><li>First-generation antipsychotics </li></ul><ul><ul><li>Dopamine receptor antagonists </li></ul></ul><ul><li>Second-generation antipsychotics </li></ul><ul><ul><li>Serotonin dopamine antagonists (SDAs) </li></ul></ul>
  13. 13. Families of Antipsychotics <ul><li>Phenothiazines </li></ul><ul><ul><li>Aliphatic </li></ul></ul><ul><ul><ul><li>Chlorpromazine </li></ul></ul></ul><ul><ul><ul><li>Promazine </li></ul></ul></ul><ul><ul><ul><li>Triflupromazine </li></ul></ul></ul><ul><ul><li>Piperazine </li></ul></ul><ul><ul><ul><li>Acetophenazine </li></ul></ul></ul><ul><ul><ul><li>Fluphenazine </li></ul></ul></ul><ul><ul><ul><li>Perphenazine </li></ul></ul></ul><ul><ul><ul><li>Proclorphenazine </li></ul></ul></ul><ul><ul><ul><li>Trifluroperazine </li></ul></ul></ul><ul><ul><ul><li>Mesoridazine </li></ul></ul></ul><ul><ul><ul><li>Thioridazine </li></ul></ul></ul>
  14. 14. Families of Antipsychotics <ul><li>Thioxantines </li></ul><ul><ul><li>Dibenzoxapine </li></ul></ul><ul><ul><ul><li>Chlorproxitene </li></ul></ul></ul><ul><ul><ul><li>Thiothixene </li></ul></ul></ul><ul><ul><li>Dihydroindole </li></ul></ul><ul><ul><ul><li>Molindone </li></ul></ul></ul><ul><ul><li>Butyrophenones </li></ul></ul><ul><ul><ul><li>Droperidol </li></ul></ul></ul><ul><ul><ul><li>Haloperidol </li></ul></ul></ul>
  15. 15. Families of Antipsychotics <ul><li>Thioxantenes cont. </li></ul><ul><ul><li>Dyphenylbutylpiperidine </li></ul></ul><ul><ul><ul><li>Primozide </li></ul></ul></ul><ul><ul><li>Benzamide </li></ul></ul><ul><ul><ul><li>Sulpiride (not available in the U.S.) </li></ul></ul></ul><ul><ul><li>Rauwolfia Alkaloid </li></ul></ul><ul><ul><ul><li>Reserpine </li></ul></ul></ul>
  16. 16. DRAs <ul><li>Therapeutic indications </li></ul><ul><ul><li>Indicated for many types of psychiatric and neurologic disorders. </li></ul></ul><ul><ul><ul><ul><li>See table 36.18-2 pg 1045 </li></ul></ul></ul></ul>
  17. 17. Pharmacotherapy <ul><li>Chlorpromazine (Thorazine) </li></ul><ul><ul><li>Introduced in 1952 </li></ul></ul><ul><ul><li>Most important single contribution to the treatment of a psychiatric illness </li></ul></ul><ul><ul><li>Effective at reducing hallucinations and delusions as well as excitement </li></ul></ul><ul><ul><li>Antipsychotics reduce relapse rates </li></ul></ul><ul><ul><li>Apprx. 70% of patients treated with antipsychotics achieve remission </li></ul></ul>
  18. 18. Pharmacotherapy <ul><li>Acute Psychosis </li></ul><ul><ul><li>Lasts 4-8 weeks </li></ul></ul><ul><ul><li>Severe agitation as a result of: </li></ul></ul><ul><ul><ul><li>Frightening delusions </li></ul></ul></ul><ul><ul><ul><li>Hallucinations </li></ul></ul></ul><ul><ul><ul><li>Suspiciousness </li></ul></ul></ul><ul><ul><ul><li>Other causes: </li></ul></ul></ul><ul><ul><ul><ul><li>Stimulant abuse </li></ul></ul></ul></ul>
  19. 19. Pharmacotherapy <ul><li>Therapeutic options </li></ul><ul><ul><li>Acute psychosis </li></ul></ul><ul><ul><li>Antipsychotics (DRAs) </li></ul></ul><ul><ul><ul><li>Highly agitated patients: IM antipsychotics offer relatively fast relief </li></ul></ul></ul><ul><ul><ul><li>High Potency </li></ul></ul></ul><ul><ul><ul><ul><li>Haloperidol (Haldol) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Acetophenazine (Tindal) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Fluphenazine (Prolixin, Permitil) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Perphenacin (Trilafon) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Thiotixene (Navane) </li></ul></ul></ul></ul>
  20. 20. Pharmacotherapy <ul><ul><li>Antipsychotics (DRAs) cont. </li></ul></ul><ul><ul><li>Low Potency </li></ul></ul><ul><ul><ul><li>Chlorpromazine (Thorazine) </li></ul></ul></ul><ul><ul><ul><li>Loxapine (Loxitane) </li></ul></ul></ul><ul><ul><ul><li>Mesoridazine (Serentil) </li></ul></ul></ul><ul><ul><ul><li>Molindone (Moban) </li></ul></ul></ul><ul><ul><ul><li>Pimozide (Orap) </li></ul></ul></ul><ul><ul><ul><li>Thioridazine (Mellaril) </li></ul></ul></ul>
  21. 21. Possible Adverse Effects of DRAs <ul><li>Seizures </li></ul><ul><ul><li>May lower seizure threshold </li></ul></ul><ul><li>Sedation </li></ul><ul><li>Central and peripheral anticholinergic effects </li></ul><ul><li>Cardiac effects </li></ul><ul><li>Sudden death </li></ul><ul><li>Orthostatic (postural) hypotension </li></ul><ul><li>Hematologic effects </li></ul><ul><li>Endocrine effects </li></ul><ul><li>Skin and eye </li></ul><ul><li>Jaundice </li></ul><ul><li>Overdoses </li></ul><ul><ul><li>Exagerated DRAs effects </li></ul></ul><ul><li>Pregnacy and lactation </li></ul><ul><ul><li>Related to malformations </li></ul></ul><ul><li>Interactions </li></ul><ul><ul><li>See table 36.18-5 </li></ul></ul>
  22. 24. Pharmacotherapy <ul><li>Atypical Antipsychotics </li></ul><ul><ul><li>Serotonin Dopamine antagonists (SDAs) </li></ul></ul><ul><ul><ul><li>Effective in patients that present aggressive or violent behavior (10% of patients) </li></ul></ul></ul><ul><ul><ul><li>Treatment with SDAs decreases suicide risks and water intoxication in patients with schizophrenia </li></ul></ul></ul><ul><ul><li>Adverse effects </li></ul></ul><ul><ul><ul><li>SDAs share similar spectrum of adverse reactions, but differ in frequency and severity </li></ul></ul></ul><ul><ul><ul><li>See table 36.30-1 pg 1093, Kapplan & Sadock </li></ul></ul></ul>
  23. 25. Pharmacotherapy <ul><li>Olanzapine </li></ul><ul><ul><li>Effective in psychosis, and in the tratment of agitation in patients with schizophrenia </li></ul></ul><ul><li>Clozapine </li></ul><ul><ul><li>Effective in controlling psychosis but due to life- threatening adverse effects, appropriate only to non-responsive patients </li></ul></ul><ul><ul><li>Also effective in patients that present severe tardive dyskinesia. </li></ul></ul><ul><ul><li>Benzisoxazoles </li></ul></ul><ul><ul><ul><li>Risperidone (Risperdal) </li></ul></ul></ul>
  24. 27. Pharmacotherapy <ul><ul><li>Benzodiazeoines- Effective for agitation during acute psychosis </li></ul></ul><ul><ul><ul><li>Lorazepam (Ativan) – may reduce the amount of antipsychotic needed </li></ul></ul></ul>

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