Schizophrenia and Antipsychotic Treatment Stacy Weinberg

Schizophrenia and Antipsychotic Treatment

• Stacy Weinberg

• 3 April 2007

What is it?

Types

• Catatonic Type

• Either in position or speech (imitating others)
• Very rare

• Disorganized Type

• Disturbance in behavior, speech, and thought
• Flat affect, eccentric

• Paranoid Type

• Delusions and auditory hallucinations
• Cognitive functioning remains intact

• Residual Type

• Have been previously diagnosed but no longer show prominent symptoms; still have other symptoms

• Undifferentiated Type

Positive Symptoms

• Disturbances of thought processes

• Delusions

• Hallucinations

• Erratic/extreme emotions

• Very slow or fast movement, catatonia

• Behavioral changes

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

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

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

Types of Drug Treatment

• Typical Antipsychotics

• Dopamine antagonists

• Atypical Antipsychotics

• 5-hydroxytryptamine effect, also effect dopamine

• Combination Drugs

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.

Typical - Phenothiazines

• Dopamine D2 receptor antagonists

• Chlorpromazine first developed from promethazine, first tricyclic antihistamine

Haloperidol

• Butyrophenone

• Used in 1970s almost exclusively

• No anticholinergic effects – therefore used in patients with delirium

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

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

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)

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)

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

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