Predicting response to clozapine - Status of current research

Clozapine, the prototype for the new generation of atypical antipsychotics, has demonstrated efficacy in treating schizophrenia, particularly in patie nts with symptoms that are refractory to traditional antipsychotics. Unfort unately, clozapine is associated with agranulocytosis in a small but signif icant minority of patients. Reliable predictors of response, whether therap eutic or adverse, to clozapine would assist clinicians in using this drug m ore effectively. This article reviews some of the proposed mechanisms of action of clozapine , and surveys current research on potential predictors of favourable and ad verse outcomes to clozapine treatment. Demographic factors, plasma clozapin e concentrations, neurochemical measures at baseline, response to pharmacol ogical challenges, neuroimaging and molecular genetics have all been consid ered. Although conclusive, sensitive and specific predictors of response to clozapine have yet to be identified, significant associations have been fo und for predictors of both favourable response and adverse effects.