The effectiveness of olanzapine in treatment-refractory schizophrenia whenpatients are nonresponsive to or unable to tolerate clozapine

Objective: This multicenter, open-label study was designed to assess the ef ficacy and tolerability of olanzapine in patients with chronic schizophreni a who are resistant to therapy with classic neuroleptic agents and are eith er not responsive to or unable to tolerate clozapine. Methods: Patients received olanzapine orally once daily for 18 weeks at dos es ranging from 5 to 25 mg. The primary efficacy measure was change in the total score on the Positive and Negative Syndrome Scale (PANSS) from baseli ne to end point. Secondary efficacy measures were the total score on the Br ief Psychiatric Rating Scale (BPRS); the PANSS positive, negative, general psychopathology, and mood subscores; and the Clinical Global Impression imp rovement score. Also recorded were spontaneously reported adverse events; e xtrapyramidal symptoms (assessed by the Abnormal Involuntary Movement Scale , Simpson-Angus Scale, and Barnes Akathisia Scale); vital signs; and clinic al laboratory test results. Results: Forty-eight patients were treated with olanzapine; of these, 45 we re assessable over the full Is-week study period. Total scores on the PANSS and BPRS were reduced from baseline by an average of 17.7 (14.2%) and 9.8 points (20.2%), respectively. Eighteen patients (40.0%) experienced a treat ment response, defined as a reduction in PANSS total score of greater than or equal to 20%. A total of 25 patients (55.6%) achieved a similar reductio n in BPRS total score. Significant reductions were seen in both the positiv e and negative symptom scores on the PANSS (P < 0.001). Olanzapine was well tolerated, with minimal treatment-emergent adverse events or clinically re levant changes in vital signs or clinical laboratory test results. No clini cally significant blood dyscrasias were observed in olanzapine-treated pati ents, including those who had discontinued clozapine because of treatment-a ssociated leukopenia or neutropenia. Conclusion: The results of this study suggest that olanzapine may be of ben efit in patients who are refractory to or unable to tolerate clozapine.