Pfizer Inc, 235 East 42nd St, New York, NY 10017, USA.
J Clin Psychiatry. 2011 Mar;72(3):367-75. doi: 10.4088/JCP.10m06281gre.
A pooled analysis was conducted to identify possibly suicide-related adverse events in Pfizer-sponsored, phases 2-4, placebo-controlled, double-blind, adult and pediatric completed randomized controlled trials of ziprasidone and to evaluate the risk of suicidality with ziprasidone versus placebo.
The trials included were initiated as early as June 1992, and the cutoff date for selection of the placebo-controlled trials in the Pfizer database was October 2, 2009. The US Food and Drug Administration (FDA)-defined search methodology was used to identify possibly suicide-related adverse events, and the Columbia Classification Algorithm of Suicide Assessment (primary outcome measure) was used to categorize them. The incidences of possibly suicide-related adverse events were calculated for individual classifications and for the predefined combined categories of suicidality (comprising classification codes 1-4) and suicidal behavior (comprising classification codes 1-3), along with the ziprasidone versus placebo relative risks and corresponding 95% CIs. Exact binomial 95% CIs were calculated for the individual treatment group incidences.
Suicidality events were identified in 52 among 5,123 subjects treated with either ziprasidone or placebo in 22 trials. No cases of completed suicide occurred in this analysis. There were no statistically significant differences between ziprasidone and placebo in any of the individual classification categories, combined suicidal behavior category (ziprasidone vs placebo relative risk = 0.67; 95% CI, 0.206-2.201), or combined suicidality risk category (ziprasidone vs placebo relative risk = 0.90; 95% CI, 0.514-1.563).
Results of our analyses, performed in accordance with the FDA-specified search strategy, reveal no significant differences in treatment-emergent suicidality risk in ziprasidone versus placebo subjects treated in controlled clinical trials.
采用荟萃分析的方法，识别辉瑞赞助的、2 至 4 期、安慰剂对照、双盲、成人和儿科完成的随机对照试验中与可能自杀相关的不良事件，并评估与安慰剂相比，齐拉西酮的自杀风险。
纳入的试验最早于 1992 年 6 月启动，辉瑞数据库中选择安慰剂对照试验的截止日期为 2009 年 10 月 2 日。采用美国食品药品监督管理局（FDA）定义的搜索方法识别与可能自杀相关的不良事件，并采用自杀评估哥伦比亚分类算法（主要结局指标）对其进行分类。计算各分类和自杀（包含分类代码 1-4）和自杀行为（包含分类代码 1-3）的预先定义综合分类的不良事件的发生率，以及齐拉西酮与安慰剂的相对风险和相应的 95%可信区间。采用确切二项式 95%可信区间计算各治疗组的发生率。
在 22 项试验中，5123 例接受齐拉西酮或安慰剂治疗的受试者中，共 52 例发生自杀事件。本分析中无自杀完成病例。在任何单一分类中，齐拉西酮与安慰剂之间均无统计学差异，包括联合自杀行为分类（齐拉西酮与安慰剂的相对风险=0.67；95%可信区间，0.206-2.201）和联合自杀倾向分类（齐拉西酮与安慰剂的相对风险=0.90；95%可信区间，0.514-1.563）。
根据 FDA 规定的搜索策略进行的分析结果显示，在对照临床试验中，接受齐拉西酮治疗与安慰剂治疗的患者在治疗中出现的自杀倾向风险无显著差异。
