Predicting response to clozapine: Status of current research

Rona J. Hu, Anil K. Malhotra, David Pickar

Research output: Contribution to journalArticlepeer-review


Clozapine, the prototype for the new generation of atypical antipsychotics, has demonstrated efficacy in treating schizophrenia, particularly in patients with symptoms that are refractory to traditional antipsychotics. Unfortunately, clozapine is associated with agranulocytosis in a small but significant minority of patients. Reliable predictors of response, whether therapeutic or adverse, to clozapine would assist clinicians in using this drug more effectively. This article reviews some of the proposed mechanisms of action of clozapine, and surveys current research on potential predictors of favourable and adverse outcomes to clozapine treatment. Demographic factors, plasma clozapine concentrations, neurochemical measures at baseline, response to pharmacological challenges, neuroimaging and molecular genetics have all been considered. Although conclusive, sensitive and specific predictors of response to clozapine have yet to be identified, significant associations have been found for predictors of both favourable response and adverse effects.

Original languageEnglish (US)
Pages (from-to)317-326
Number of pages10
JournalCNS Drugs
Issue number4
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Neuropsychology and Physiological Psychology


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