Relationship Between Neurotransmitter Receptor Polymorphisms, Plasma Concentrations and Clinical Response to Clozapine

Primary Outcome Measures:

• Brief Psychiatric Rating Scale [ Time Frame: entry, 3 wks, 5 wks, 8 wks, 4 mo, 6 mo ] [ Designated as safety issue: No ]
  

Secondary Outcome Measures:

• Scale for the Assessment of Positive Symptoms [ Time Frame: entry, wk 3, wk 5, wk 8, 4 mo, 6 mo ] [ Designated as safety issue: No ]
  
• Scale for the assessment of Negative symptoms [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: No ]
  
• Calgary Depression Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: No ]
  
• Abnormal Involuntary Movement Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: Yes ]
  
• Barnes Akathisia Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: Yes ]
  

Patients age 18-65 with a DSM IV diagnosis of schizophrenia who have a history of nonresponse to conventional atypical antipsychotics and who are to be treated with clozapine by their psychiatrist, will be asked to participate at or near the time clozapine therapy is initiated. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) will be performed on all subjects at entry into the study, at 3 weeks, 5 weeks, 8 weeks, and at 4 and 6 months. Adverse effects will be monitored with the Simpson-Angus Scale, Barnes Akathisia scale and the AIMS at each of these time points. The Calgary Depression Scale will also be administered at each visit. A complete neurocognitive assessment battery will be completed at entry and at 6 months for those subjects willing to undergo neurocognitive testing. It is anticipated not all subjects will complete neurocognitive testing. A blood or cheek swab sample will be collected at study entry for DNA analysis. Plasma blood levels will be collected at weeks 3, 5, 8 and study completion for measurement of clozapine plasma concentrations. The subject's weight, BMI, smoking status and concomitant medications will be recorded at each visit.