奥氮平治疗老年痴呆症患者临床试验期间出现的治疗中突发不良事件综述。

A review of treatment-emergent adverse events during olanzapine clinical trials in elderly patients with dementia.

作者信息

Kryzhanovskaya Ludmila A, Jeste Dilip V, Young Carrie A, Polzer John P, Roddy Tamra E, Jansen Joe F, Carlson Janice L, Cavazzoni Patrizia A

机构信息

Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, IN 46285-6156, USA.

出版信息

J Clin Psychiatry. 2006 Jun;67(6):933-45. doi: 10.4088/jcp.v67n0610.

DOI:10.4088/jcp.v67n0610

PMID:16848653

Abstract

OBJECTIVE

Olanzapine and other antipsychotics are not approved by the U.S. Food and Drug Administration to treat behavioral disturbances associated with dementia, but they are often prescribed to these patients. Although antipsychotics may be efficacious in this population, elderly patients with dementia may be particularly vulnerable to adverse events. This article reviews the safety of olanzapine in elderly patients with dementia.

DATA SOURCES

Data from 6 studies comparing olanzapine to placebo, risperidone, or conventional antipsychotics in elderly patients with dementia were analyzed for mortality, cerebrovascular adverse events (CVAEs), and other adverse events. These trials represent all Lilly olanzapine-comparator trials in this population. The data included integration of 5 double-blind, placebo-controlled studies (olanzapine, N = 1184; placebo, N = 478; median age = 79 years; 1 study also compared olanzapine with risperidone, N = 196) and an open-label study comparing olanzapine (N = 150) with conventional antipsychotics (N = 143).

DATA SYNTHESIS

Incidence of mortality was significantly higher in olanzapine- (3.5%) than in placebo-treated patients (1.5%; p = .024). There were no significant differences in the crude incidence of mortality between olanzapine- (2.9%) and risperidone- (2.0%) or olanzapine- (14.8%) and conventional antipsychotic-treated patients (16.1%; p = .871). Risk factors associated with mortality in olanzapine-treated patients included age >/= 80, concurrent benzodiazepine use, treatment-emergent sedation, or treatment-emergent pulmonary conditions. Incidence of CVAEs was approximately 3 times higher in olanzapine- (1.3%) than in placebo-treated patients (0.4%). There were no significant differences in the incidence of CVAEs between olanzapine- (2.5%) and risperidone- (2.0%; p = 1.0) or olanzapine- (3.4%) and conventional antipsychotic-treated patients (4.3%; p = .765).

CONCLUSION

These findings should be considered if prescribers elect to treat behavioral disturbances associated with dementia in the elderly with olanzapine or other antipsychotics.

摘要

目的

奥氮平及其他抗精神病药物未获美国食品药品监督管理局批准用于治疗与痴呆相关的行为障碍，但这些药物却常被开给此类患者。尽管抗精神病药物可能对此类人群有效，但患有痴呆的老年患者可能特别容易出现不良事件。本文综述了奥氮平在患有痴呆的老年患者中的安全性。

数据来源

分析了6项在患有痴呆的老年患者中比较奥氮平与安慰剂、利培酮或传统抗精神病药物的研究数据，以评估死亡率、脑血管不良事件（CVAEs）及其他不良事件。这些试验代表了礼来公司在此类人群中进行的所有奥氮平对照试验。数据包括整合5项双盲、安慰剂对照研究（奥氮平组，N = 1184；安慰剂组，N = 478；中位年龄 = 79岁；1项研究还比较了奥氮平与利培酮，N = 196）以及1项开放标签研究，该研究比较了奥氮平（N = 150）与传统抗精神病药物（N = 143）。

数据综合

奥氮平治疗组的死亡率（3.5%）显著高于安慰剂治疗组（1.5%；p = 0.024）。奥氮平治疗组（2.9%）与利培酮治疗组（2.0%）或奥氮平治疗组（14.8%）与传统抗精神病药物治疗组（16.1%；p = 0.871）之间的粗死亡率无显著差异。奥氮平治疗患者中与死亡率相关的危险因素包括年龄≥80岁、同时使用苯二氮䓬类药物、治疗中出现的镇静或治疗中出现的肺部疾病。奥氮平治疗组的CVAEs发生率（1.3%）约为安慰剂治疗组（0.4%）的3倍。奥氮平治疗组（2.5%）与利培酮治疗组（2.0%；p = 1.0）或奥氮平治疗组（3.4%）与传统抗精神病药物治疗组（4.3%；p = 0.765）之间的CVAEs发生率无显著差异。