schizophrenia

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schizophrenia

• characterized by positive and negative symptoms
• positive symptoms those that can be observed
  ex. hallucinations
• negative symptoms absence of normal behaviors
  lack of affect anhedonia,

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treatment options

• positive symptoms
• majority of traditional neuroleptics reduce
  positive symptoms
• negative symptoms
• majority of traditional neuroleptics have no
  effect on negative symptoms
• originally thought that negative symptoms were
  simply an indicator of brain damage
• new thought atypical neuroleptics also appear
  to reduce negative symptoms

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traditional neuroleptics

• traditional neuroleptics chlorpromazine
  (Thorazine), haloperidol (Haldol)
• ability to block positive symptoms linked to
  high well the drug binds to and blocks D2
  receptors
• DA theory for schizophrenia
• too much DA activity responsible for symptoms
• reduce DA activity, reduce positive symptoms

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DA pathways

• mesolimbic
• emotion, reward, may be responsible for
  symptoms
• nigrostriatal
• motor movement, extrapyramidal motor system
• degeneration associated with Parkinsons disease

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problems with traditional neuroleptics

• parkinson like side effects
• early on see symptoms in virtually all
  schizophrenics that were similar to PD
• extrapyramidal motor side effects
• motor induced akinesias paucity of movement
• akathesia uncontrolled restlessness, constant
  compulsive movements
• tardive dyskinesia
• avoid it by periodically changing meds atypical
  neuroleptics?
• relatively safe- therapeutic index is as high as
  1000
• malignant neuroleptic syndrome
• reduces sexual interest and ability

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atypical neuroleptics

• clozapine (Clozaril)
• works on positive and negative symptoms
• reduced motor side effects
• more selective at binding to DA R (and does not
  bind as potently)
• also blocks ACh, histamine, 5HT

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problems with clozapine

• risk of agranulocytosis (1)
• requires weekly blood testing
• only used for treatment resistant schizophrenia
  or those nontolerant to conventional
  antipsychotics (ie motor side effects)

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some other atypicals

• risperidone (Risperdal)
• olanzapine (Zyprexa)
• potential increased risk for diabetes
• quietiapine (Seroquel)
• aripiprazole (Abilify)

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other atypical neuroleptics

• do not produce agranulocytosis
• block 5HT2 receptors and ACh receptors
• less motor side effects than traditional
  neuroleptics (?)
• appear able to reduce negative symptoms
• appear to be somewhat less sedating (?)
• at lower risk for producing tardive dyskinesia
  (?)
• improvement can be more rapid
• not all are generic yet

reduction in noncompliance
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negative side of the atypicals

• weight gain-
• 20 40 lbs average but can be much more!
• still have anticholinergic side effects
• dry mouth, memory problems, urinary retention
• tachycardia
• direct costs can be up to 100X greater than
  typical neuroleptics

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(No Transcript)
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tolerance, dependence, wd, animal self
administration?

• no (except to parkinson like symptoms maybe), no,
  no and no