Clinical Predictors of Response to Clozapine Treatment in Ambulatory Patients With Schizophrenia

Background: Despite the advent of new atypical antipsychotics, clozapine remains an important option in the treatment of patients with poor response to conventional antipsychotics. Clinicians would be well served if clinical characteristics could be identified that predict a favorable response to clozapine. A few studies addressing this issue have reported inconsistent results.

Method: The association of clinical characteristics with a sustained response was investigated in 37 partially treatment-refractory outpatients with a DSM-III-R diagnosis of chronic schizophrenia who had been assigned to clozapine treatment in a double-blind, haloperidol-controlled, long-term (29-week) study of clozapine. Response was defined as a 20% decrease of the Brief Psychiatric Rating Scale (BPRS) psychosis factor score sustained over 2 consecutive ratings. Differences between responders and nonresponders with regard to selected baseline variables were analyzed with t tests and χ² tests. In addition, Cox regression analyses were performed to identify variables that best predicted a response to clozapine treatment.

Results: Clozapine responders were rated as less severely ill, showed a lesser degree of negative symptoms, and demonstrated fewer extrapyramidal side effects at baseline as compared with nonresponders. In addition, higher BPRS total scores—after controlling for the effects of the other variables—were associated with a response.

Conclusion: In a cohort of partially treatment-refractory outpatients, a favorable response to clozapine was associated with characteristics describing less severely ill patients. The history of patients did not affect their response to clozapine.