CLINICAL EFFECTS OF CLOZAPINE IN CHRONIC-SCHIZOPHRENIA - RESPONSE TO TREATMENT AND PREDICTORS OF OUTCOME

Objective: This study addressed the unique clinical properties attribu ted to the atypical antipsychotic clozapine, including its efficacy in patients with treatment-refractory psychosis and against negative sym ptoms, its lack of acute extrapyramidal side effects, and the longer t ime course of its therapeutic effects. Method: The clinical responses of 84 schizophrenic inpatients (66 with treatment-refractory illness a nd 18 who were intolerant of antipsychotic treatment) were examined. A fter all previous antipsychotic medications had been withdrawn, the pa tients were treated with clozapine according to a standardized titrati on and dosage schedule. Patients who tolerated and responded to treatm ent were discharged and maintained on a regimen of clozapine for up to 52 weeks. Patients were evaluated for behavioral response and side ef fects after weeks 3, 6, 12, 26, 39, and 52 of treatment. Results: Fift y percent of the patients with treatment-refractory illness and 76% of the treatment-intolerant patients responded to clozapine in up to 52 weeks. The optimal period for a trial of clozapine appeared to be 12-2 4 weeks. Clozapine exhibited therapeutic effects on negative symptoms, but these were not clearly independent of its effects on positive sym ptoms and extrapyramidal side effects. Several variables, including ea rly age at onset of illness and female gender, were found to be predic tors of poor response to treatment. Predictors of good response includ ed the presence of extrapyramidal side effects during previous treatme nt with classic neuroleptics and a diagnosis of paranoid schizophrenia . Conclusions: These findings have important implications for the use of clozapine and our understanding of the pathophysiology of treatment -resistant schizophrenia.