1. 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”,

2. 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

3. 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

4. DA pathways mesolimbic – –emotion, reward, may be responsible for + symptoms nigrostriatal – –motor movement, extrapyramidal motor system degeneration associated with Parkinsons disease

5. 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

6. 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

7. 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)

8. some other atypicals risperidone (Risperdal) olanzapine (Zyprexa) –potential increased risk for diabetes quietiapine (Seroquel) aripiprazole (Abilify)

9. 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

10. 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

12. tolerance, dependence, wd, animal self administration? no (except to parkinson like symptoms maybe), no, no and no