Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, 1 Bowdoin Sq, Boston, MA 02114, USA.
J Clin Psychiatry. 2012 Oct;73(10):1300-6. doi: 10.4088/JCP.11r07485.
To investigate the relationship between specific levels of placebo response rates and the drug response rate and the relative risk of response to drug versus placebo in clinical trials of antidepressant monotherapy and adjunctive polypharmacy for MDD.
MEDLINE/PubMed databases were searched for studies published in the English language between January 1980 and March 2011 by using the search terms depression, placebo, augmentation, adjunct, adjunctive, and each of the antidepressant agents identified. The search was supplemented by manual bibliographic review and examination of relevant review articles.
The analysis included randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for MDD, 4 weeks or longer, and of augmentation/combination treatments for antidepressant partial responders/nonresponders with MDD, 1 week or longer. 169 antidepressant monotherapy studies and 35 adjunctive polypharmacy studies were found eligible for inclusion in our analysis.
Data extracted included number of patients enrolled, patient characteristics, drug dosages and scheme (fixed vs flexible dosing), duration of the trial, and response rates.
In antidepressant monotherapy studies, a higher placebo response rate correlated with a lower risk ratio of responding to antidepressant versus placebo (P < .001) and correlated with higher antidepressant response rates (P < .001); the number needed to treat (NNT) for response was approximately 4, 6, and 9 in trials with placebo response rates < 30%, ≥ 30% and < 40%, and ≥ 40%, respectively. In adjunctive trials, a higher placebo response rate correlated with a lower risk ratio of responding to the adjunctive drug versus placebo (P < .001) and correlated with a trend toward statistical significance with higher response rates to the adjunctive drug (P = .050); the NNT was approximately 6, 7, 11, and 17 in trials with placebo response rates < 20%, ≥ 20% and < 30%, ≥ 30% and < 40%, and ≥ 40%, respectively.
These results suggest that the relative efficacy of the active drug compared to placebo in clinical trials for MDD is highly heterogeneous across studies with different placebo response rates, with a worse performance in showing a superiority of the drug versus placebo for studies with placebo response rates ≥ 30% and ≥ 40%, respectively, for monotherapy and adjunctive trials. It is important to maintain placebo response rates below this critical threshold, since this is one of the most challenging obstacles for new treatment development in MDD.
探讨特定的安慰剂反应率水平与药物反应率之间的关系，以及在抗抑郁药单药治疗和辅助多药治疗 MDD 的临床试验中，药物与安慰剂的相对反应风险。
使用抑郁、安慰剂、增效、辅助、辅助和确定的每种抗抑郁药等术语，在 1980 年 1 月至 2011 年 3 月期间，在 MEDLINE/PubMed 数据库中检索发表的英文文献。该搜索通过手动书目审查和检查相关综述文章进行补充。
分析包括随机、双盲、安慰剂对照的抗抑郁药单药治疗 MDD 的试验，疗程为 4 周或更长时间，以及抗抑郁药部分反应者/无反应者的增效/联合治疗，疗程为 1 周或更长时间。发现 169 项抗抑郁药单药治疗研究和 35 项辅助多药治疗研究符合纳入分析的条件。
提取的数据包括入组患者人数、患者特征、药物剂量和方案（固定剂量与灵活剂量）、试验持续时间和反应率。
在抗抑郁药单药治疗研究中，较高的安慰剂反应率与抗抑郁药与安慰剂相比的风险比降低（P<0.001）相关，并且与较高的抗抑郁药反应率相关（P<0.001）；在安慰剂反应率<30%、≥30%和<40%、≥40%的试验中，治疗反应的所需治疗人数（NNT）分别约为 4、6 和 9。在辅助治疗试验中，较高的安慰剂反应率与辅助药物与安慰剂相比的风险比降低（P<0.001）相关，并且与辅助药物的反应率呈统计学意义上的趋势相关（P=0.050）；在安慰剂反应率<20%、≥20%和<30%、≥30%和<40%、≥40%的试验中，NNT 分别约为 6、7、11 和 17。
这些结果表明，在 MDD 的临床试验中，与安慰剂相比，活性药物的相对疗效在具有不同安慰剂反应率的研究中具有高度异质性，对于安慰剂反应率分别≥30%和≥40%的单药治疗和辅助治疗研究，药物相对于安慰剂的优越性表现更差。重要的是要将安慰剂反应率保持在这个关键阈值以下，因为这是新的 MDD 治疗方法开发中最具挑战性的障碍之一。
Zotero 插件