Hunter Aimee M, Cook Ian A, Tartter Molly, Sharma Simi K, Disse Gregory D, Leuchter Andrew F
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, 760 Westwood Plaza, Rm. 57-455, Los Angeles, CA, 90024-1759, USA,
Psychopharmacology (Berl). 2015 Oct;232(20):3833-40. doi: 10.1007/s00213-015-4047-2. Epub 2015 Aug 29.
A history of antidepressant treatment may predispose subjects toward placebo nonresponse in randomized controlled trials (RCTs) in major depressive disorder (MDD).
The objective of this study is to examine self-reported prior antidepressant treatment and response in relationship to clinical outcome in an 8-week randomized trial of reuptake inhibitor antidepressant medication (MED) versus placebo (PBO) administered along with limited supportive care.
Chi-square and MMRM analyses examined MED vs. PBO outcomes in antidepressant-naïve vs. antidepressant-experienced subjects. Linear regression models examined treatment history along with covariates as predictors of clinical improvement.
Among completers (n = 56), there was no significant difference in response rate between MED (53.3 %) and PBO (42.3 %) (χ (2) = 0.33, p = 0.28, 1-tailed). The antidepressant-experienced subgroup (n = 37), however, showed a significantly greater response rate to MED (52.4 %) than PBO (25.0 %) (χ (2) = 2.82, p = 0.047, 1-tailed). The full intent-to-treat (ITT) sample (n = 69) did not show a significant difference between MED and PBO group improvement over time, but in the treatment-experienced subgroup (n = 46), MED showed significantly greater improvement than PBO (coefficient = .39, SE = .23, p = .045, 1-tailed). A history of prior antidepressant treatment predicted poorer overall response independent of pretreatment symptom severity, number or length of previous episodes, subject expectations, or family history of MDD.
Treatment history appears to constitute a factor that is distinct from other commonly studied illness characteristics or expectancy measures, and that impacts overall response as well as drug-placebo separation in RCTs.
在重度抑郁症（MDD）的随机对照试验（RCT）中，抗抑郁药治疗史可能使受试者出现对安慰剂无反应的情况。
本研究的目的是在一项为期8周的随机试验中，研究自我报告的既往抗抑郁药治疗及反应与临床结局之间的关系，该试验将再摄取抑制剂抗抑郁药物（MED）与安慰剂（PBO）配合有限的支持性治疗进行给药。
卡方检验和混合效应重复测量模型（MMRM）分析比较了未使用过抗抑郁药的受试者与有抗抑郁药使用经验的受试者中MED与PBO的治疗结果。线性回归模型将治疗史及协变量作为临床改善的预测因素进行分析。
在完成试验的受试者（n = 56）中，MED组（%）与PBO组（%）的缓解率无显著差异（χ(2) = 0.33，p = 0.28，单尾）。然而，有抗抑郁药使用经验的亚组（n = 37）中，MED组的缓解率（%）显著高于PBO组（%）（χ(2) = 2.82，p = 0.047，单尾）。全意向性分析（ITT）样本（n = 69）中，MED组和PBO组随时间的改善情况无显著差异，但在有治疗经验的亚组（n = 46）中，MED组的改善情况显著优于PBO组（系数 = 0.39，标准误 = 0.23，p = 0.045，单尾）。既往抗抑郁药治疗史预示着总体反应较差，且与治疗前症状严重程度、既往发作次数或时长、受试者期望或MDD家族史无关。
治疗史似乎是一个与其他常见研究的疾病特征或期望指标不同的因素，它会影响RCT中的总体反应以及药物-安慰剂差异。
