Trajectories of Depression Severity in Clinical Trials of Duloxetine Insights Into Antidepressant and Placebo Responses
Trajectories of Depression Severity in Clinical Trials of Duloxetine Insights Into Antidepressant and Placebo Responses
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DOI：
10.1001/archgenpsychiatry.2011.132
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发表时间：
2011-12-01
影响因子：
--
通讯作者：
Krystal, John H.
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文献类型：
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作者：
Gueorguieva, Ralitza;Mallinckrodt, Craig;Krystal, John H.
内容：抑郁症临床试验失败的高比例可能是由于高安慰剂应答率和标准统计方法未能捕获治疗应答的异质性。目的：评估生长混合模型是否可以提供对抑郁症患者临床试验中抗抑郁剂和安慰剂应答的见解。设计：我们重新分析了度洛西汀的临床试验，以确定治疗期间汉密尔顿抑郁量表（HAM-D）评分的不同轨迹。我们分析了整个样本的轨迹，然后分别分析了所有活性组和所有安慰剂组的轨迹。评估了盐酸度洛沙汀、选择性5-羟色胺再摄取抑制剂（SSRI）和协变量对遵循特定轨迹概率的影响。使用混合效应模型比较不同轨迹的结果。设置：七项随机双盲临床试验，比较度洛沙汀与安慰剂和对照SSRI。患者：共2515例重度抑郁症患者。干预：度洛沙汀和对照SSRI。主要结果测量：HAM-D总分。结果：在整个样本和抗抑郁药治疗的子样本中，我们确定了应答者（76.3%的样本）和无应答者（23.7%的样本）的轨迹。然而，安慰剂治疗患者的特征为单一缓解轨迹。度洛西汀和SSRI在疗效上没有差异，与安慰剂相比，它们显著降低了遵循无应答者轨迹的几率。抗抑郁药应答者随着时间的推移有显着更好的HAM-D评分比安慰剂治疗的患者，但抗抑郁药无应答者随着时间的推移有显着更差的HAM-D评分比安慰剂治疗的patients.Conclusions：大多数患者治疗的抗抑郁药的临床轨迹随着时间的推移，是上级的安慰剂治疗的患者。然而，一些接受这些药物的患者比接受安慰剂的患者表现更差。这些数据强调了在阿糖胞苷能抗抑郁药治疗期间持续监测药物风险和获益的重要性。他们应该进一步刺激寻找生物标志物或其他预测反应状态的指导抗抑郁药治疗。
Context: The high percentage of failed clinical trials in depression may be due to high placebo response rates and the failure of standard statistical approaches to capture heterogeneity in treatment response.Objective: To assess whether growth mixture modeling can provide insights into antidepressant and placebo responses in clinical trials of patients with major depression.Design: We reanalyzed clinical trials of duloxetine to identify distinct trajectories of Hamilton Scale for Depression (HAM-D) scores during treatment. We analyzed the trajectories in the entire sample and then separately in all active arms and in all placebo arms. Effects of duloxetine hydrochloride, selective serotonin reuptake inhibitor (SSRI), and covariates on the probability of following a particular trajectory were assessed. Outcomes in different trajectories were compared using mixed-effects models.Setting: Seven randomized double-blind clinical trials of duloxetine vs placebo and comparator SSRI.Patients: A total of 2515 patients with major depression.Interventions: Duloxetine and comparator SSRI.Main Outcome Measure: Total score on the HAM-D.Results: In the entire sample and in the antidepressant-treated subsample, we identified trajectories of responders (76.3% of the sample) and nonresponders (23.7% of the sample). However, placebo-treated patients were characterized by a single response trajectory. Duloxetine and SSRI did not differ in efficacy, and compared with placebo they significantly decreased the odds of following the nonresponder trajectory. Antidepressant responders had significantly better HAM-D scores over time than placebo-treated patients, but antidepressant nonresponders had significantly worse HAM-D scores over time than the placebo-treated patients.Conclusions: Most patients treated with serotonergic antidepressants showed a clinical trajectory over time that is superior to that of placebo-treated patients. However, some patients receiving these medications did more poorly than patients receiving placebo. These data highlight the importance of ongoing monitoring of medication risks and benefits during serotonergic antidepressant treatment. They should further stimulate the search for biomarkers or other predictors of responder status in guiding antidepressant treatment.