Beasley C M, Dornseif B E, Bosomworth J C, Sayler M E, Rampey A H, Heiligenstein J H, Thompson V L, Murphy D J, Masica D N
Division of Clinical Neurosciences, Eli Lilly and Company, Indianapolis, Indiana 46285.
BMJ. 1991 Sep 21;303(6804):685-92. doi: 10.1136/bmj.303.6804.685.
A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation).
Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both.
Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment.
Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson's chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296).
Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.
进行一项临床试验数据的综合荟萃分析，以评估氟西汀与自杀行为（自杀行为和自杀意念）之间可能存在的关联。
对17项针对重度抑郁症患者的双盲临床试验汇总数据进行回顾性分析，比较氟西汀组（n = 1765）与三环类抗抑郁药组（n = 731）或安慰剂组（n = 569），或两组同时比较。
搜索多个数据源以识别有自杀行为的患者。使用汉密尔顿抑郁评定量表第3项评估自杀意念，该量表对自杀倾向进行系统评分。显著自杀意念的出现定义为该项目评分从基线时的0或1变为双盲治疗期间的3或4；恶化定义为较基线水平有任何增加；改善定义为治疗期间最后一次访视时较基线水平降低。
氟西汀与安慰剂比较时自杀行为无显著差异（0.2%对0.2%，p = 0.494，Mantel-Haenszel调整发病率差异），与三环类抗抑郁药比较时也无显著差异（0.7%对0.4%，p = 0.419）。氟西汀的自杀行为合并发病率为0.3%，安慰剂为0.2%，三环类抗抑郁药为0.4%，氟西汀与安慰剂（p = 0.533，Pearson卡方检验）或三环类抗抑郁药（p = 0.789）比较均无显著差异。氟西汀出现自杀意念的频率略低于安慰剂（0.9%对2.6%，p = 0.094），在数值上也低于三环类抗抑郁药（1.7%对3.6%，p = 0.102）。显著自杀意念出现的合并发病率，氟西汀为1.2%，安慰剂为2.6%，三环类抗抑郁药为3.6%。氟西汀的发病率显著低于安慰剂（p = 0.042）和三环类抗抑郁药（p = 0.001）。氟西汀和安慰剂组自杀意念任何程度的恶化情况相似（15.4%对17.9%，p = 0.196），氟西汀和三环类抗抑郁药组也相似（15.6%对16.3%，p = 0.793）。自杀意念恶化的合并发病率，氟西汀为15.3%，安慰剂为17.9%，三环类抗抑郁药为16.3%。氟西汀与安慰剂（p = 0.141）或三环类抗抑郁药（p = 0.542）比较发病率无显著差异。氟西汀治疗后自杀意念改善显著优于安慰剂（72.0%对54.8%，p＜0.001），与三环类抗抑郁药的改善情况相似（72.5%对69.8%，p = 0.294）。自杀意念改善的合并发病率，氟西汀为72.2%，安慰剂为54.8%，三环类抗抑郁药为69.8%。氟西汀的发病率显著高于安慰剂（p＜0.001），与三环类抗抑郁药比较无差异（p = 0.296）。
这些试验的数据未显示氟西汀与抑郁症患者自杀行为风险增加或显著自杀念头出现有关。
