TREATMENT OF PSYCHOTIC DISORDERS

 

I             Target Symptoms for Pharmacotherapy

1.                 Positive psychotic symptoms - hallucinations, delusions, thought disorder, paranoia

2.                 Negative symptoms - flat affect, social withdrawal

3.                 Cognitive symptoms - neuropsychological impairments

4.                 5%-10% full recovery rate in schizophrenia with or without Rx

5.                 30% good, partial response, 30% inadequate partial response, remaining refractory to Rx

 

II            Traditional Antipsychotic Drugs

6.                 Chlorpromazine (Thorazine®, 1952) - initial development as a sedative but antipsychotic properties recognized. 

1.                 Primary action - dopamine receptor blockade.

2.                 Good response to initial psychotic episode.

3.                 Adverse events - sedation, parkinsonism, restless leg (akathesia), hypotension, constipation, weight gain, *tardive dyskinesia

 

7.                 Haloperidol (Haldol®, 1950s) - until recent development of atypical drugs, most widely used antipsychotic

1.                 Effective antipsychotic agent due to less sedation.

2.                 Significant extrapryamidal side effects - parkinsonism, tardive dyskinesia, akathesia.

3.                 High affinity for D2  family of dopamine receptors; also has affinity for 5-HT2A and noradrenergic receptors.

 

III          Newer “Atypical” Antipsychotic Agents

8.                 Clozapine (Clozaril®) - approved for use in 1990=s although drug itself is not new

1.                 Superior efficacy over traditional drugs for treatment-resistent, chronic schizophrenia.

2.                 Has affinity for a broad array of monoaminergic and other receptors in brain (DA, 5-HT, NA, ACh and histamine).

3.                 Side effects observed in traditional agents not present in clozapine, however, risk of agranulocytosis is about 1% occurring about 2-3 months after beginning treatment.

 

9.                 Olanzapine (Zyprexa®) - a structural congenger of clozapine with many of the same pharmacological properties

1.                 Affinity same as clozapine except lacks high affinity for HT7 receptors.

2.                 Clinical trials have demonstrated substantial antipsychotic response in schizophrenic patients on both positive and negative symptoms.

3.                 Appears more effective in treating negative symptoms than other antipsychotics.

4.                 Side effects minimal; no risk for agranulocytosis.

10.              Quetiapine (Seroquel®) - different chemical class but pharmacological action similar to clozapine except has no affinity for muscarine cholinergic receptors

1.                 Efficacy appears similar to haloperidol but without the motor side effects and risk for tardive dyskinesia.

2.                 Good effect on positive symptoms, unclear how effective for negative symptoms.

3.                 Very benign side effect profile.

 

IV          Even Newer Antipsychotic Agents - Dopamine and Serotonin Receptor Antagonists

1.                 Risperidone (Risperdal®)

1.                 High affinity for 5-HT2A and D2 receptors but about 20 times higher affinity for 5-HT2A  receptors.

2.                 Treatment studies worldwide have shown dramatic reduction in positive and negative symptoms.

3.                 No significant motor side effects until dosage exceeds 10 mg/day.

4.                 Weight gain and increased obsessive compulsive behavior (due to serotonin blockade) most common behavioral side effects.

 

2.                 Ziprasidone (Geodon®, Approved 2001)

1.                 Developed based on similar receptor binding profile seen in risperidone but also has unique reuptake blockade properties at 5-HT and NA reuptake sites.

2.                 Given its more selective pharmacological action, ziprasidone may show good potential for psychotic disorders which also have a prominent mood component.

3.                 Published studies of its efficacy, based on controlled clinical trials, have yet to appear.  Drug company has released lot of information on its efficacy.

4.                 No motor side effects, behavioral side effects also reported to be minimal.

 

V           Psychological Therapies

1.                 Relatively few good studies investigating effect of traditional psychotherapies.

2.                 Major limiting factor may be the cognitive and neuropsychological symptoms of psychosis which make insight-oriented or behavioral therapies more difficult to implement.

3.                 Discharge to group home environments which maintain the structure of the institution may help some patients.

4.                 Relapse rate among schizophrenia is very high which may wipe out psychotherapeutic gains achieved.