Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, 260 Stetson Street, Suite 3200, Cincinnati, OH 45267-0559, United States; Department of Pediatrics, Divisions of Clinical Pharmacology and Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Carl H. Lindner College of Business, University of Cincinnati, Cincinnati, OH, United States.
J Affect Disord. 2022 Feb 1;298(Pt A):292-300. doi: 10.1016/j.jad.2021.10.047. Epub 2021 Oct 31.
Treatment studies of children and adolescents with internalizing disorders suggest that the combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT) consistently produces greater improvement than either treatment alone. We sought to determine how response to combined treatment varies across disorders (anxiety versus depression), and by specific patient characteristics.
Three large National Institutes of Health-funded trials of children and adolescents with major depression (n = 2) and anxiety disorders (n = 1) were evaluated, each comparing CBT + SSRI to SSRI only, Bayesian Hierarchical Models (BHMs) were used, for endpoint response, time course of response and predictors of response in participants who received SSRI or SSRI+CBT.
SSRI+CBT significantly decreased symptoms by week 4 (p<0.001) across disorders. This improvement continued at week 8 and 12 (p<0.001); however, the additive benefit of CBT over SSRI monotherapy was not statistically significant until week 12 (p<0.001). The fastest response to SSRI+CBT was for patients who were younger, with milder baseline anxiety/depression symptoms and depressive disorders. The slowest response for SSRI+CBT was for boys, adolescents, minoritized children, those with severe symptoms and externalizing disorders.
Limitations included inconsistent moderators, variation in the number of observations over time and a lack of genetic or pharmacokinetic variables related to SSRI exposure across studies.
The superiority of SSRI+CBT for youth with depression and anxiety is further supported. For purposes of rapid and greater relief, combination treatment is the superior approach across anxiety and depression and is robust to a range of participant characteristics. However, the added value of CBT (with an SSRI) occurs late in treatment. These findings represent a step towards understanding heterogeneity of treatment response and raise the possibility that interventions could be better tailored or adapted based on patient characteristics.
儿童和青少年内化障碍治疗研究表明，选择性 5-羟色胺再摄取抑制剂（SSRI）与认知行为疗法（CBT）联合治疗的效果明显优于单一治疗。我们旨在确定联合治疗对不同疾病（焦虑与抑郁）的反应如何变化，以及受特定患者特征的影响。
对三项由美国国立卫生研究院资助的儿童和青少年重度抑郁症（n=2）和焦虑障碍（n=1）的临床试验进行了评估，每项研究均比较了 CBT+SSRI 与 SSRI 单药治疗，使用贝叶斯层次模型（BHMs），用于终点反应、反应过程和接受 SSRI 或 SSRI+CBT 的参与者的反应预测因素。
在跨疾病中，SSRI+CBT 在第 4 周（p<0.001）显著降低了症状。这种改善在第 8 周和第 12 周（p<0.001）持续；然而，CBT 对 SSRI 单药治疗的附加益处直到第 12 周才具有统计学意义（p<0.001）。对 SSRI+CBT 反应最快的是年龄较小、基线焦虑/抑郁症状较轻和抑郁障碍的患者。对 SSRI+CBT 反应最慢的是男孩、青少年、少数族裔儿童、症状严重和伴有外化障碍的儿童。
限制因素包括不一致的调节剂、随时间变化的观察数量的变化以及缺乏与研究间 SSRI 暴露相关的遗传或药代动力学变量。
SSRI+CBT 对青少年抑郁和焦虑的优越性进一步得到支持。为了更快和更大程度地缓解，联合治疗是治疗焦虑和抑郁的首选方法，对一系列患者特征具有稳健性。然而，CBT（与 SSRI 联合使用）的附加价值在治疗后期出现。这些发现代表了理解治疗反应异质性的一步，并提出了基于患者特征对干预措施进行更好地定制或调整的可能性。
