Hammad Tarek A, Laughren Thomas P, Racoosin Judith A
Division of Neuropharmocological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993-0002, USA.
J Clin Psychopharmacol. 2006 Apr;26(2):203-7. doi: 10.1097/01.jcp.0000203198.11453.95.
Concerns have been raised about the appropriateness of placebo controls in clinical trials for major depressive disorder (MDD), given that there are approved treatments for this illness. Critics have argued that patients with untreated depression would be exposed to an unnecessary risk of suicide. There is also a competing concern that antidepressant drug treatment itself may induce suicidal behavior and thinking (suicidality). To examine this question, we have evaluated the rate of suicide in placebo- and active drug-treated groups of patients with MDD and various anxiety disorders participating in short-term randomized controlled trials (RCTs). We examined data from all manufacturer-sponsored short-term RCTs of 9 commonly used antidepressants in patients with MDD and various anxiety disorders. All short-term RCTs of antidepressants in patients with MDD and various anxiety disorders were included. Individual patients' data were available for all trials. Data were available for the 207 trials conducted in patients with MDD, including a total of 40,028 patients. There were 21 cases of suicide in these patients. Forty-four trials were conducted in patients with various anxiety disorders, including a total of 10,972 patients. There were 2 cases of suicide in these patients. Overall, at least 1 case of suicide occurred in 21 of the 251 trials. Sixteen of the suicides in MDD trials occurred in trials that had only an active control comparison group, and most of these (14 cases) were observed in the non-North American trials. In the placebo-controlled MDD trials, the rate ratios of suicide in the combined drug groups compared with placebo were 1.07 (0.1-63.4) and 0.5 (0.0-36.7) for the non-North American and North American trials, respectively. In the anxiety disorder studies, the overall rate ratio of suicide for the selective serotonin reuptake inhibitors compared with placebo was 0.9 (0.0-71.4). Neither use of placebo nor of antidepressants in short-term RCTs was associated with an increased risk of completed suicide among patients with MDD or various anxiety disorders. Nonetheless, because of the small numbers of suicides in these trials and the subsequent lack of statistical power, an increased risk of completed suicide in association with either drug or placebo treatment cannot be definitively excluded.
鉴于重度抑郁症（MDD）已有获批的治疗方法，人们对MDD临床试验中安慰剂对照的合理性提出了担忧。批评者认为，未经治疗的抑郁症患者会面临不必要的自杀风险。还有一个与之相矛盾的担忧是，抗抑郁药物治疗本身可能会诱发自杀行为和想法（自杀倾向）。为了研究这个问题，我们评估了参与短期随机对照试验（RCT）的MDD及各种焦虑症患者中，接受安慰剂治疗组和接受活性药物治疗组的自杀率。我们研究了所有由制药商赞助的、针对MDD及各种焦虑症患者使用9种常用抗抑郁药的短期RCT数据。纳入了所有针对MDD及各种焦虑症患者的抗抑郁药短期RCT。所有试验都有个体患者的数据。有针对MDD患者进行的207项试验的数据，共涉及40,028名患者。这些患者中有21例自杀。针对各种焦虑症患者进行了44项试验，共涉及10,972名患者。这些患者中有2例自杀。总体而言，251项试验中有21项至少发生了1例自杀。MDD试验中的16例自杀发生在仅设有活性对照比较组的试验中，其中大多数（14例）出现在非北美试验中。在安慰剂对照的MDD试验中，非北美试验和北美试验中，联合用药组与安慰剂组相比的自杀率比分别为1.07（0.1 - 63.4）和0.5（0.0 - 36.7）。在焦虑症研究中，选择性5-羟色胺再摄取抑制剂与安慰剂相比的总体自杀率比为0.9（0.0 - 71.4）。在短期RCT中，无论是使用安慰剂还是抗抑郁药，都与MDD或各种焦虑症患者的自杀完成风险增加无关。尽管如此，由于这些试验中的自杀案例数量较少，随后缺乏统计学效力，因此不能明确排除与药物或安慰剂治疗相关的自杀完成风险增加的可能性。
