Evidence for the effectiveness of olanzapine among patients nonresponsive and/or intolerant to risperidone.

BACKGROUND: This multicenter, open-label study evaluated the efficacy and safety of olanzapine in patients with schizophrenia who had been nonresponsive or intolerant to a course of risperidone (mean duration of risperidone treatment = 46.3 days). METHOD: A total of 34 patients with DSM-III-R and ICD-9 schizophrenia entered this trial. Twenty-five patients were nonresponsive to previous risperidone treatment, 6 patients were intolerant to the risperidone treatment, and 3 patients listed both reasons for discontinuation of risperidone. Patients were treated across a dose range of 5 to 25 mg/day of olanzapine. The primary efficacy variable was baseline to endpoint change in Positive and Negative Syndrome Scale (PANSS) score. Safety was assessed using the Clinical Global Impressions-Severity of Illness scale. RESULTS: Improvement from baseline PANSS score (mean +/- SD PANSS score = 119.4 +/- 26.9) was evident at the week-6 midpoint (-22.2 +/- 19.5) and at the week-14 endpoint (-28.7 +/- 22.3). On average, severity ratings were reduced from baseline by 25% after 14 weeks of olanzapine therapy. Twenty olanzapine-treated patients (58.8%) achieved the a priori-defined response criterion of > or = 20% reduction in PANSS total score. Among patients who met the response criterion, 50% (10/20) had done so by the fourth week. These clinical improvements occurred across a broad range of symptom domains and included reductions in PANSS positive, negative, general psychopathology, and mood subscores. No statistically significant differences were found on any efficacy measure at any visit between the patients who were nonresponsive to risperidone compared with those who were intolerant to risperidone. Olanzapine was well tolerated, with no subject discontinuing early owing to an intolerable adverse event that could be conclusively linked to olanzapine. CONCLUSION: The results of this open-label study suggest that olanzapine may be an effective alternative for schizophrenic patients who are nonresponsive and/or intolerant to risperidone treatment. Moreover, the results underscore the differential pharmacology that exists among the newer antipsychotic agents.

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

OBJECTIVE: This multicenter, open-label study was designed to assess the efficacy and tolerability of olanzapine in patients with chronic schizophrenia who are resistant to therapy with classic neuroleptic agents and are either not responsive to or unable to tolerate clozapine. METHODS: Patients received olanzapine orally once daily for 18 weeks at doses 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 baseline to end point. Secondary efficacy measures were the total score on the Brief Psychiatric Rating Scale (BPRS); the PANSS positive, negative, general psychopathology, and mood subscores; and the Clinical Global Impression improvement score. Also recorded were spontaneously reported adverse events; extrapyramidal symptoms (assessed by the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, and Barnes Akathisia Scale); vital signs; and clinical laboratory test results. RESULTS: Forty-eight patients were treated with olanzapine; of these, 45 were assessable over the full 18-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 treatment response, defined as a reduction in PANSS total score of > or = 20%. A total of 25 patients (55.6%) achieved a similar reduction in BPRS total score. Significant reductions were seen in both the positive and negative symptom scores on the PANSS (P < 0.001). Olanzapine was well tolerated, with minimal treatment-emergent adverse events or clinically relevant changes in vital signs or clinical laboratory test results. No clinically significant blood dyscrasias were observed in olanzapine-treated patients, including those who had discontinued clozapine because of treatment-associated leukopenia or neutropenia. CONCLUSION: The results of this study suggest that olanzapine may be of benefit in patients who are refractory to or unable to tolerate clozapine.