Predictors and markers of clozapine response.
BACKGROUND
With other atypical antipsychotics now available, having predictors of clozapine response would be of considerable value, offering clinicians guidance in their decision as to when, and if, a trial of clozapine is warranted.


OBJECTIVE
The aim was to review existing evidence regarding identified predictors and markers of clozapine response.


METHODS
Relevant studies were identified through PUBMED searches (1975-June 2004) and cross-referencing of reviews and included studies. The data were summarized under two main categories: clinical (general, neurological, cognitive/neuropsychological, clozapine levels) and biological (biochemical, endocrine, genetic, metabolic, morphological, dopamine D2 receptor occupancy). 'Reliable' predictors/markers were defined a priori as those with support of at least two independent reports that addressed overall response, with no contradictory findings to date. 'Potential' predictors/markers had the support of a single report that addressed overall response and at least one other evaluating treatment outcome but not directly addressing response status.


CONCLUSIONS
Higher baseline clinical symptoms and functioning in the previous years and low cerebrospinal homovanillic acid/5-hydroxyindoleacetic acid levels were identified as reliable. Three potential measures were identified: reduction of frontal cortex metabolic activity, reduction of caudate volume, and improvement in P50 sensory gating.
Chung
Carmen
C
Centre for Addiction and Mental Health, Schizophrenia Program, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.
Remington
Gary
G
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D003024:Clozapine / Q000627:therapeutic use*; D006801:Humans; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology
D014150:Antipsychotic Agents; D015415:Biomarkers; D003024:Clozapine
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