Predictors of clozapine response in schizophrenia.
The introduction of the atypical neuroleptic, clozapine, has had widespread influence not only on the treatment of the seriously mentally ill patient, but also on new drug development and on hypotheses of the pathophysiology of schizophrenia. While clozapine differs from traditional neuroleptics in its lack of extrapyramidal side effects (EPS), it also is distinct in its profile of neurotransmitter receptor affinities. In our work examining the clinical and biological effects of clozapine in patients with schizophrenia, we have identified the presence of EPS during typical neuroleptic treatment as a consistent predictor of subsequent good response to clozapine. Further, our data suggest that clozapine should not be reserved for the most chronically ill patients, but rather be utilized in patients with less chronic courses of schizophrenia. Biological predictors of clozapine response are consistent with dopaminergic, serotonergic, and noradrenergic facets to its mechanism of action.
Pickar
D
D
National Institute of Mental Health, Experimental Therapeutics Branch, National Institutes of Health, Bethesda, Md 20892.
Owen
R R
RR
Litman
R E
RE
Hsiao
J K
JK
Su
T P
TP
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000453:epidemiology; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005476:Fluphenazine / Q000627:therapeutic use; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D011336:Probability; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D017981:Receptors, Neurotransmitter; D006897:Hydroxyindoleacetic Acid; D003024:Clozapine; D005476:Fluphenazine; D006719:Homovanillic Acid