Sanger T M, Lieberman J A, Tohen M, Grundy S, Beasley C, Tollefson G D
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Am J Psychiatry. 1999 Jan;156(1):79-87. doi: 10.1176/ajp.156.1.79.
It has been hypothesized that the morbidity and mortality associated with schizophrenia can be prevented by providing effective treatment during the first episode of psychosis. Hence, the authors examined patients with first-episode psychosis to determine the efficacy and safety of olanzapine and haloperidol treatment.
A subpopulation of first-episode patients (N=83) from a large prospective, multicenter, international, double-blind, 6-week acute treatment study was evaluated. These patients were selected from a pool of 1,996 patients who had a DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder and who also met the following criteria: 1) the length of their current psychotic episode had to be 5 or fewer years, and 2) patients had to be 45 years of age or younger at onset of first psychotic symptoms.
Compared to haloperidol, olanzapine showed a statistically significantly greater reduction in the Brief Psychiatric Rating Scale (BPRS) total and negative scores and in the Positive and Negative Syndrome Scale total and positive scores. Clinical response (defined as 40% or greater improvement in BPRS total score from baseline) was also statistically significantly higher in olanzapine-treated patients (67.2%) than in haloperidol-treated patients (29.2%). Olanzapine-treated patients further showed statistically significant improvements in the Simpson-Angus scale and Barnes Akathisia Scale scores, while haloperidol-treated patients showed a worsening on both measures. Compared to olanzapine-treated multiple-episode patients in the parent study, olanzapine-treated first-episode patients achieved an even statistically significantly higher response. Haloperidol-treated first-episode patients experienced statistically significantly more extrapyramidal symptoms than haloperidol-treated multiple-episode patients.
In patients experiencing first-episode psychosis, olanzapine had a risk-benefit profile significantly superior to that of haloperidol. The study results suggest that novel antipsychotic agents such as olanzapine should be considered as a preferred option in first-episode psychosis, on the basis of both safety and efficacy advantages.
有假设认为，通过在精神病发作的首次发作期间提供有效治疗，可以预防与精神分裂症相关的发病率和死亡率。因此，作者对首次发作精神病患者进行了检查，以确定奥氮平和氟哌啶醇治疗的疗效和安全性。
对来自一项大型前瞻性、多中心、国际性、双盲、为期6周的急性治疗研究的首次发作患者亚组（N = 83）进行了评估。这些患者是从1996名被诊断为精神分裂症、分裂情感性障碍或精神分裂症样障碍的患者中挑选出来的，他们还符合以下标准：1）当前精神病发作的时长必须为5年或更短，2）患者首次出现精神病症状时的年龄必须在45岁或以下。
与氟哌啶醇相比，奥氮平在简明精神病评定量表（BPRS）总分及阴性得分以及阳性和阴性综合征量表总分及阳性得分方面的降低具有统计学显著意义。奥氮平治疗的患者临床反应（定义为BPRS总分较基线改善40%或更多）在统计学上也显著高于氟哌啶醇治疗的患者（67.2%对29.2%）。奥氮平治疗的患者在辛普森-安格斯量表和巴恩斯静坐不能量表得分上进一步显示出统计学显著改善，而氟哌啶醇治疗的患者在这两项指标上均出现恶化。与母研究中奥氮平治疗的多发作患者相比，奥氮平治疗的首次发作患者在统计学上的反应甚至更高。氟哌啶醇治疗的首次发作患者比氟哌啶醇治疗的多发作患者经历了统计学上显著更多的锥体外系症状。
在首次发作精神病患者中，奥氮平的风险效益比明显优于氟哌啶醇。研究结果表明，基于安全性和疗效优势，像奥氮平这样的新型抗精神病药物应被视为首次发作精神病的首选药物。
