Background

Better understanding of the heterogeneity of treatment responses could help to improve care for adolescents with depression. We analysed data from a clinical trial to assess whether specific symptom clusters responded differently to various treatments.

Methods

For this secondary analysis, we used data from the Treatment for Adolescents with Depression Study (TADS), in which 439 US adolescents aged 12–17 with a DSM-IV diagnosis of major depressive disorder and a minimum score of 45 on the Children's Depression Rating Scale-Revised (CDRS-R) were randomly assigned (1:1:1:1) to treatment with fluoxetine, cognitive behavioural therapy (CBT), fluoxetine plus CBT, or pill placebo. Our analysis focuses on the acute phase of the trial (ie, the first 12 weeks). Groups of co-occurring symptoms were established by clustering scores for each CDRS-R item at baseline with Ward's method, with Euclidean distances for hierarchical agglomerative clustering. We then used a linear mixed-effects model to investigate the relationship between symptom clusters and treatment efficacy, with the sum of symptom scores within each cluster as the dependent measure. As fixed effects, we entered cluster, time, and treatment assignment, with all two-way and three-way interactions, into the model. The random effect providing better fit was established to be a by-subject random slope for cluster based on improvement in the Schwarz-Bayesian information criterion.

Outcomes

We identified two symptom clusters: cluster 1 comprised depressed mood, difficulty having fun, irritability, social withdrawal, sleep disturbance, impaired schoolwork, excessive fatigue, and low self-esteem, and cluster 2 comprised increased appetite, physical complaints, excessive weeping, decreased appetite, excessive guilt, morbid ideation, and suicidal ideation. For cluster 1 symptoms, CDRS-R scores were reduced by 5·8 points (95% CI 2·8–8·9) in adolescents treated with fluoxetine plus CBT, and by 4·1 points (1·1–7·1) in those treated with fluoxetine, compared with those given placebo. For cluster 2 symptoms, no significant differences in improvements in CDRS-R scores were detected between the active treatment and placebo groups.

Interpretation

Response to fluoxetine and CBT among adolescents with depression is heterogeneous. Clinicians should consider clinical profile when selecting therapeutic modality. The contrast in response patterns between symptom clusters could provide opportunities to improve treatment efficacy by gearing the development of new therapies towards the resolution of specific symptoms.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico.

中文翻译：

---

青少年抑郁症的症状群和对治疗的差异性反应：抑郁症青少年治疗的次级分析研究随机试验

背景

更好地了解治疗反应的异质性可能有助于改善青少年抑郁症的护理。我们分析了一项来自临床试验的数据，以评估特定症状群对各种疗法的反应是否不同。

方法

对于该次要分析，我们使用了《青少年抑郁症治疗研究》（TADS）的数据，其中有439位12-17岁的美国青少年通过DSM-IV诊断为重度抑郁症，并且儿童抑郁评分最低分数为45量表修订版（CDRS-R）被随机分配（1：1：1：1）进行氟西汀，认知行为疗法（CBT），氟西汀加CBT或药丸安慰剂治疗。我们的分析集中在试验的急性期（即前12周）。通过使用Ward's方法在基线将每个CDRS-R项目的得分进行聚类，并使用欧氏距离进行聚类聚类，来确定并发症状的分组。然后，我们使用线性混合效应模型研究症状簇与治疗效果之间的关系，每个群集中症状评分的总和作为相关度量。作为固定效果，我们将群集，时间和治疗分配以及所有双向和三向交互输入到模型中。基于Schwarz-Bayesian信息准则的改进，将提供更好拟合的随机效应确定为集群的受试者随机性斜率。

结果

我们确定了两个症状群集：群集1包括情绪低落，娱乐困难，烦躁，社交退缩，睡眠障碍，学业受损，过度疲劳和自尊心低；群集2包括食欲增加，身体不适，过度哭泣，情绪低落。食欲，内，病态和自杀意念。对于群1症状，用氟西汀加CBT治疗的青少年的CDRS-R得分降低了5·8分（95％CI 2·8-8·9），降低了4·1分（1·1-7·1） ）与使用安慰剂的患者相比，用氟西汀治疗的患者）。对于第2类症状，在积极治疗组和安慰剂组之间CDRS-R评分的改善没有显着差异。

解释

抑郁症青少年对氟西汀和CBT的反应不同。选择治疗方式时，临床医生应考虑临床情况。症状群之间反应模式的对比可能会提供机会，通过着眼于解决特定症状的新疗法的发展来提高治疗效果。

资金

全国国防科技委员会。