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”,
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
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
DA pathways
• mesolimbic –
– emotion, reward, may be responsible for +
symptoms
• nigrostriatal –
– motor movement, extrapyramidal motor
system
• degeneration associated with Parkinsons disease
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
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
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)
some other atypicals
• risperidone (Risperdal)
• olanzapine (Zyprexa)
– potential increased risk for diabetes
• quietiapine (Seroquel)
• aripiprazole (Abilify)
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
negative side of the atypicals
• weight gain20 – 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
tolerance, dependence, wd, animal
self administration?
• no (except to parkinson like symptoms
maybe), no, no and no