Predicting Response to Clozapine

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.