Olanzapine in Treatment-Refractory Schizophrenia

BACKGROUND: Clozapine is currently the treatment of choice for neuroleptic-resistant schizophrenia. Olanzapine is a new antipsychotic drug that has shown efficacy against positive and negative symptoms of schizophrenia, with minimal extrapyramidal side effects. However, the effectiveness of olanzapine has not yet been reported among treatment-refractory schizophrenic patients. METHOD: A total of 25 schizophrenic patients (DSM-IV criteria) with documented lack of response to two conventional antipsychotic drugs entered this 6-week prospective, open-label treatment trial with olanzapine 15 to 25 mg/day. An optional extension up to 6 months was provided. RESULTS: As a group, the olanzapine-treated patients showed statistically significant improvement (p < .05) in both positive and negative symptoms by the end of 6 weeks of therapy. Overall, 9 of the patients (36%) met the a priori criteria for treatment-response (> or = 35% decrease in Brief Psychiatric Rating Scale [BPRS] total score, plus posttreatment Clinical Global Impression-Severity < or = 3 or BPRS total < 18). Only one patient discontinued treatment because of an adverse event during the study. Despite the relatively high dosages of olanzapine used, there were no reports of parkinsonism, akathisia, or dystonia, and no patients required anticholinergic medication. CONCLUSION: This open study suggests that olanzapine may be effective and well tolerated for a substantial number of neuroleptic-resistant schizophrenic patients. Further blinded, controlled trials are needed to confirm our results.