Strawn Jeffrey R, Dobson Eric T, Mills Jeffrey A, Cornwall Gary J, Sakolsky Dara, Birmaher Boris, Compton Scott N, Piacentini John, McCracken James T, Ginsburg Golda S, Kendall Phillip C, Walkup John T, Albano Anne Marie, Rynn Moira A
1 Department of Psychiatry and Behavioral Neuroscience, College of Medicine, University of Cincinnati , Cincinnati, Ohio.
2 Division of Child and Adolescent Psychiatry, Department of Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
J Child Adolesc Psychopharmacol. 2017 Aug;27(6):501-508. doi: 10.1089/cap.2016.0198. Epub 2017 Apr 6.
The aim of this study is to identify predictors of pill placebo response and to characterize the temporal course of pill placebo response in anxious youth.
Data from placebo-treated patients (N = 76) in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multisite, randomized controlled trial that examined the efficacy of cognitive-behavioral therapy, sertraline, their combination, and placebo for the treatment of separation, generalized, and social anxiety disorders, were evaluated. Multiple linear regression models identified features associated with placebo response and models were confirmed with leave-one-out cross-validation. The likelihood of improvement in patients receiving pill placebo-over time-relative to improvement associated with active treatment was determined using probabilistic Bayesian analyses.
Based on a categorical definition of response (Clinical Global Impressions-Improvement Scale score ≤2), nonresponders (n = 48), and pill placebo responders (n = 18) did not differ in age (p = 0.217), sex (p = 0.980), race (p = 0.743), or primary diagnosis (all ps > 0.659). In terms of change in anxiety symptoms, separation anxiety disorder and treatment expectation were associated with the degree of pill placebo response. Greater probability of placebo-related anxiety symptom improvement was observed early in the course of treatment (baseline to week 4, p < 0.0001). No significant change in the probability of placebo-related improvement was observed after week 4 (weeks 4-8, p = 0.07; weeks 8-12, p = 0.85), whereas the probability of improvement, in general, significantly increased week over week with active treatment.
Pill placebo-related improvement occurs early in the course of treatment and both clinical factors and expectation predict this improvement. Additionally, probabilistic approaches may refine our understanding and prediction of pill placebo response.
本研究旨在确定丸剂安慰剂反应的预测因素，并描述焦虑青少年中丸剂安慰剂反应的时间进程。
对儿童/青少年焦虑多模式研究（CAMS）中接受安慰剂治疗的患者（N = 76）的数据进行评估，该研究是一项多中心随机对照试验，检验了认知行为疗法、舍曲林、二者联合及安慰剂治疗分离性、广泛性和社交焦虑症的疗效。多元线性回归模型确定了与安慰剂反应相关的特征，并通过留一法交叉验证对模型进行了确认。使用概率贝叶斯分析确定接受丸剂安慰剂治疗的患者相对于接受积极治疗的患者随时间改善的可能性。
根据反应的分类定义（临床总体印象改善量表评分≤2），无反应者（n = 48）和丸剂安慰剂反应者（n = 18）在年龄（p = 0.217）、性别（p = 0.980）、种族（p = 0.743）或主要诊断方面无差异（所有p值>0.659）。在焦虑症状变化方面，分离焦虑症和治疗期望与丸剂安慰剂反应程度相关。在治疗早期（基线至第4周，p < 0.0001）观察到安慰剂相关焦虑症状改善的可能性更大。第4周后（第4 - 8周，p = 0.07；第8 - 12周，p = 0.85），安慰剂相关改善的概率未观察到显著变化，而总体而言，积极治疗后改善的概率逐周显著增加。
丸剂安慰剂相关的改善发生在治疗早期，临床因素和期望均可预测这种改善。此外，概率方法可能会完善我们对丸剂安慰剂反应的理解和预测。
