Tran P V, Hamilton S H, Kuntz A J, Potvin J H, Andersen S W, Beasley C, Tollefson G D
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Clin Psychopharmacol. 1997 Oct;17(5):407-18. doi: 10.1097/00004714-199710000-00010.
Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.
奥氮平和利培酮均为第二代抗精神病药物，代表了两种不同的药理学策略。尽管它们具有一些体外特性，但因其化学结构、受体结合亲和力谱、动物神经药理学、药代动力学以及体内神经影像学特征而有所不同。基于这些差异，人们推测这两种化合物会表现出不同的安全性和/或疗效特征。为验证这一假设，对339名符合精神分裂症、分裂样精神障碍或精神分裂症伴情感障碍DSM-IV标准的患者进行了一项国际多中心双盲平行组前瞻性研究，为期28周。研究结果表明，奥氮平和利培酮在治疗精神病性症状方面均安全有效。然而，奥氮平在阴性症状（阴性症状评定量表总分）以及总体缓解率（阳性和阴性症状量表总分下降≥40%）方面显示出显著更高的疗效。此外，根据Kaplan-Meier生存曲线，接受奥氮平治疗的患者在28周时维持缓解的比例在统计学上显著高于接受利培酮治疗的患者。接受奥氮平治疗的患者锥体外系副作用、高催乳素血症和性功能障碍的发生率在统计学上显著低于接受利培酮治疗的患者。此外，接受奥氮平治疗的患者报告的不良事件在统计学上显著少于接受利培酮治疗的患者。因此，这两种药物不同的临床前特征在一项对照临床研究中也很明显。奥氮平似乎具有风险与获益优势。
