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

Martin R.K. Dossenbach, Jean Noel Beuzen, Moshe Avnon, Robert H. Belmaker, Avner Elizur, Mordechai Mark, Hanan Munitz, Michael Schneidman, David Shoshani, Petra Kratky, Starr Lee Grundy, Gary D. Tollefson

Research output: Contribution to journalArticlepeer-review


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 ≥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.

Original languageEnglish
Pages (from-to)1021-1034
Number of pages14
JournalClinical Therapeutics
Issue number9
StatePublished - 2000
Externally publishedYes


  • Chronic schizophrenia
  • Clozapine
  • Olanzapine
  • Open-label
  • Treatment-refractory


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