Breier A, Hamilton S H
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Biol Psychiatry. 1999 Feb 15;45(4):403-11. doi: 10.1016/s0006-3223(98)00291-1.
There is relatively little information regarding the efficacy of newer atypical antipsychotic drugs for patients with schizophrenia who are treatment-resistant to neuroleptic agents. Several lines of evidence suggest that a clinical trial of olanzapine in this population is warranted.
A subpopulation of patients (n = 526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, 6-week study assessing the efficacy and safety of olanzapine and haloperidol were examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted.
Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, comorbid depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale, akathisia as measured by Barnes Akathisia Scale, and extrapyramidal symptoms as measured by Simpson-Angus Extrapyramidal Rating Scale with both LOCF and completers analyses. In addition, olanzapine was significantly superior to haloperidol for Brief Psychiatric Rating Scale total (p = .006), PANSS total (p = .005), and PANSS positive symptoms (p = .017) in completers of the 6-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-treated (35%) patients in the LOCF analysis (p = .008), but significance was not reached in the completers analysis (p = .093). Mean doses (+/- SD) of olanzapine and haloperidol were 11.1 +/- 3.4 mg/day and 10.0 +/- 3.6 mg/day, respectively.
Olanzapine was superior to haloperidol for key symptom domains and parkinsonian side effects. Implications of these data for the therapeutics of this severely ill subgroup are discussed.
对于对神经阻滞剂治疗耐药的精神分裂症患者，关于新型非典型抗精神病药物疗效的信息相对较少。有几条证据表明，对该人群进行奥氮平的临床试验是有必要的。
从一项大型前瞻性双盲6周研究中选取符合治疗耐药标准的患者亚组（n = 526），该研究评估了奥氮平和氟哌啶醇的疗效与安全性。进行了末次观察结转（LOCF）分析和完成者（观察病例）分析。
在LOCF分析和完成者分析中，奥氮平在阳性和阴性症状量表（PANSS）阴性症状、由蒙哥马利-阿斯伯格抑郁评定量表评估的共病抑郁症状、由巴恩斯静坐不能量表测量的静坐不能以及由辛普森-安格斯锥体外系评定量表测量的锥体外系症状方面，均显示出从基线的平均改善显著更大。此外，在6周研究的完成者中，奥氮平在简明精神病评定量表总分（p = .006）、PANSS总分（p = .005）和PANSS阳性症状（p = .017）方面显著优于氟哌啶醇。在LOCF分析中，奥氮平治疗组（47%）的反应率显著高于氟哌啶醇治疗组（35%）（p = .008），但在完成者分析中未达到显著差异（p = .093）。奥氮平和氟哌啶醇的平均剂量（±标准差）分别为11.1 ± 3.4毫克/天和10.0 ± 3.6毫克/天。
奥氮平在关键症状领域和帕金森氏症副作用方面优于氟哌啶醇。讨论了这些数据对该重症亚组治疗的意义。
