Beuzen J N, Avnon M, Belmaker R H, Elizur A, Mark M, Munitz H, Schneidman M, Shoshani D, Kratky P, Grundy S L, Tollefson G D
Lilly Area Medical Center Vienna, Vienna, Austria.
Clin Ther. 2000 Sep;22(9):1021-34. doi: 10.1016/s0149-2918(00)80082-x.
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.
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.
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.
The results of this study suggest that olanzapine may be of benefit in patients who are refractory to or unable to tolerate clozapine.
本多中心、开放标签研究旨在评估奥氮平对经典抗精神病药物治疗无效且对氯氮平无反应或不耐受的慢性精神分裂症患者的疗效和耐受性。
患者口服奥氮平，每日一次，剂量为5至25毫克，持续18周。主要疗效指标是阳性和阴性症状量表（PANSS）总分从基线到终点的变化。次要疗效指标包括简明精神病评定量表（BPRS）总分；PANSS阳性、阴性、总体精神病理学和情绪子量表得分；以及临床总体印象改善得分。还记录了自发报告的不良事件；锥体外系症状（通过异常不自主运动量表、辛普森-安格斯量表和巴恩斯静坐不能量表评估）；生命体征；以及临床实验室检查结果。
48例患者接受了奥氮平治疗；其中45例在整个18周研究期间可进行评估。PANSS和BPRS总分较基线平均分别降低了17.7分（14.2%）和9.8分（20.2%）。18例患者（40.0%）出现治疗反应，定义为PANSS总分降低≥20%。共有25例患者（55.6%）的BPRS总分出现类似程度的降低。PANSS的阳性和阴性症状得分均显著降低（P<0.001）。奥氮平耐受性良好，治疗中出现的不良事件极少，生命体征或临床实验室检查结果也无临床相关变化。在接受奥氮平治疗的患者中，未观察到具有临床意义的血液系统异常，包括因治疗相关白细胞减少或中性粒细胞减少而停用氯氮平的患者。
本研究结果表明，奥氮平可能对难治性或不耐受氯氮平的患者有益。
