Schizophrenia and
Antipsychotic Treatment
      Stacy Weinberg
        3 April 2007
What is it?
•It is a severe, chronic, disabling brain disease
•Considered to have biological origins but exact unknown
•1%...
Types
1. Catatonic Type
  •   Either in position or speech (imitating others)
  •   Very rare
2. Disorganized Type
  •   D...
Positive Symptoms
•   Disturbances of thought processes
•   Delusions
•   Hallucinations
•   Erratic/extreme emotions
•   ...
Negative Symptoms
• Lack of interest/enjoyment in activities
• Low energy/motivation
• Blank facial expression, less facia...
Causes - Dopamine Hypothesis
• Genetic aspect
• Most think it involves dopamine:
  – Elevation of D2 monomers, decrease of...
Other Hypotheses
• Dopamine hypothesis not agreed on by
  everyone
• Some think excitatory amino acids like
  glutamate co...
Types of Drug Treatment
1. Typical Antipsychotics
  •   Dopamine antagonists
2. Atypical Antipsychotics
  •   5-hydroxytry...
Typical
• Tend to produce Extrapyramidal side
  effects:
  – Parkinsonism – tremors, rigidity, slowness of
    movement, t...
Typical - Phenothiazines
• Dopamine D2 receptor antagonists
• Chlorpromazine first developed from
  promethazine, first tr...
Haloperidol
• Butyrophenone
• Used in 1970s almost exclusively
• No anticholinergic effects – therefore used
  in patients...
Atypicals
• Atypicals do not induce EPSE
• Block D2 receptors and 5-HT seratonin
  receptors (decreases EPSE)
• As opposed...
5-HT seratonin receptors
• Blocking 5-HT seratonin receptors decreases
  negative symptoms and EPSE
  – Mechanism is unkno...
Clozapine

• First atypical (1990)
• Most dangerous atypical: risk of
  agranulocytosis (severe decrease in WBC
  count)
•...
Risperidone
• Low doses needed
• Predominantly blocks D2, then 5-HT
  – Does not exhibit multireceptor action
• Lacks anti...
Olanzapine
• Zyprexa is number one antipsychotic in
  sales (Eli Lilly)
• Exhibits multireceptor action
• Good for control...
Combinations
• Example is Symbyax
  – Combination of olanzapine and fluoxetine
    (Prozac)
  – Can also treat bipolar dis...
Schizopc Treatment
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Schizopc Treatment

  1. 1. Schizophrenia and Antipsychotic Treatment Stacy Weinberg 3 April 2007
  2. 2. What is it? •It is a severe, chronic, disabling brain disease •Considered to have biological origins but exact unknown •1% of population affected •“Schizophrenia” – split mind ● Multiple personality disorder is not schizophrenia •Psychosis is more accurate ● Severe mental illness where patient loses contact with reality ● People have problems thinking and feeling but are aware of their surroundings
  3. 3. Types 1. Catatonic Type • Either in position or speech (imitating others) • Very rare 2. Disorganized Type • Disturbance in behavior, speech, and thought • Flat affect, eccentric 3. Paranoid Type • Delusions and auditory hallucinations • Cognitive functioning remains intact 4. Residual Type • Have been previously diagnosed but no longer show prominent symptoms; still have other symptoms 5. Undifferentiated Type
  4. 4. Positive Symptoms • Disturbances of thought processes • Delusions • Hallucinations • Erratic/extreme emotions • Very slow or fast movement, catatonia • Behavioral changes
  5. 5. Negative Symptoms • Lack of interest/enjoyment in activities • Low energy/motivation • Blank facial expression, less facial variability • Inability to make or keep friends • Difficulty initiating activities • Social isolation
  6. 6. Causes - Dopamine Hypothesis • Genetic aspect • Most think it involves dopamine: – Elevation of D2 monomers, decrease of dimers – Increased release of dopamine • 2x higher • When given amphetamine, 2x more dopamine is released than control
  7. 7. Other Hypotheses • Dopamine hypothesis not agreed on by everyone • Some think excitatory amino acids like glutamate could play a role – One type of glutamate receptor, NMDA: NMDA antagonists (ex ketamine) can induce psychotic symptoms in non-schizophrenic patients – Found increase of NMDA receptors in postmortem studies of schizophrenic brains
  8. 8. Types of Drug Treatment 1. Typical Antipsychotics • Dopamine antagonists 2. Atypical Antipsychotics • 5-hydroxytryptamine effect, also effect dopamine 3. Combination Drugs
  9. 9. Typical • Tend to produce Extrapyramidal side effects: – Parkinsonism – tremors, rigidity, slowness of movement, temporary paralysis – Dystonia – involuntary muscle contractions – Akathisia – inability to resist urge to move – Tardive dyskinesia – involuntary movements of the mouth, lips, and tongue • Chewing, puckering, grimacing, etc.
  10. 10. Typical - Phenothiazines • Dopamine D2 receptor antagonists • Chlorpromazine first developed from promethazine, first tricyclic antihistamine Promethazine Chlorpromazine Trifluoperazine
  11. 11. Haloperidol • Butyrophenone • Used in 1970s almost exclusively • No anticholinergic effects – therefore used in patients with delirium
  12. 12. Atypicals • Atypicals do not induce EPSE • Block D2 receptors and 5-HT seratonin receptors (decreases EPSE) • As opposed to typicals, these are more loosely bound to D2 receptors – Easier dissociation – Shown that higher occupation of D2 receptors by drug, higher incidence of EPSE
  13. 13. 5-HT seratonin receptors • Blocking 5-HT seratonin receptors decreases negative symptoms and EPSE – Mechanism is unknown – Seratonin inhibits dopamine release – Positive symptoms associated with hyperdopaminergic condition in limbic lobe – more D2 receptors here, so D2 blocking prevails – Negative symptoms associated with hypodopaminergic condition in frontal lobe – more 5- HT receptors here, so seratonin inhibits dopamine release – stabilizes dopamine level
  14. 14. Clozapine • First atypical (1990) • Most dangerous atypical: risk of agranulocytosis (severe decrease in WBC count) • Most effective in reducing EPSE, also in reducing negative symptoms – Increases Fos-positive neurons in the prefrontal cortex (shown to affect negative symptoms)
  15. 15. Risperidone • Low doses needed • Predominantly blocks D2, then 5-HT – Does not exhibit multireceptor action • Lacks anticholinergic activity – makes it better for youth, elderly • Problem – increases prolactin levels (shouldn’t give to people with breast cancer)
  16. 16. Olanzapine • Zyprexa is number one antipsychotic in sales (Eli Lilly) • Exhibits multireceptor action • Good for controlling mood symptoms • Available in a wafer • Problems: Sedation and weight gain
  17. 17. Combinations • Example is Symbyax – Combination of olanzapine and fluoxetine (Prozac) – Can also treat bipolar disorder • Combination of ziprasidone and clozapine – Can be used to combat treatment resistance • Combination of aripriprazole and clozapine

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