Early Improvement in Individual Symptoms and Response to Antidepressants in Patients With Major Depressive Disorder
试验速览
- 阶段
- 不适用
- 入组人数
- 10,000
- 主要终点
- Response
研究概览
简要总结
Major depressive disorder (MDD) affects around 7% of the population yearly. Although effective treatments are available, only around half of all patients participating in clinical trials respond to 6 to 12 weeks of antidepressant treatment. Given these high failure rates, the ability to predict as early as possible whether a patient is (un)likely to respond would be of great value, as it would enable physicians to change treatment strategies faster.
Early improvement has consistently been found to be a strong predictor of later response. However, misclassification is still quite common, with perhaps a third of those who do not show early improvement going on to respond. Conversely, a substantial proportion of those who do show early improvement do not go on to respond. One possibility for improving the predictive power of early improvement is to examine individual symptoms, rather than the total score on a depression rating scale. Some items, for example, could reflect antidepressant side effects (e.g. gastrointestinal symptoms) and may not be very predictive.
The proposed project aims to examine the relationship between early improvement in individual symptoms and response to antidepressants in a very large patient sample. This large sample size makes it possible to use more rigorous methods than previous studies, such as the use of cross-validation to confirm the findings. It also makes it possible to examine a large set of predictors, including possible interactions among early-improving symptoms and between symptoms and demographic factors like age and gender. The added value of individual symptoms over and above using the total symptom score alone will also be examined, as well as possible differences between different antidepressant classes.
The project will use penalized (lasso) regression, which is well-suited to analyzing data with a large number of (potentially highly correlated) predictors. In the primary analysis, response after 6 weeks of treatment will be predicted. In secondary analyses, remission at week 6 and response and remission at week 12 will also be predicted.
详细描述
Study design
The proposed project is an individual patient data meta-analysis. Data will be collated from 31 trials of second-generation antidepressants for the treatment of major depressive disorder, using data from trial arms treated with placebo or Food and Drug Administration (FDA)-approved antidepressants. These trials include a total of approximately 7,800 antidepressant-treated and 3,000 placebo-treated participants. Penalized regression methods (specifically least absolute shrinkage and selection operator, 'lasso') will be used to examine the relationship between early improvement in specific depressive symptoms and response to treatment. Furthermore, the investigators will examine whether interactions among early-improving symptoms and between early-improving symptoms and demographic variables such as age and gender improve the prediction of treatment outcome. Finally, the investigators will also examine whether the prediction of response to treatment by early improvement in specific symptoms is dependent upon the type of treatment provided (placebo, selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs]), which would suggest a drug-specific mechanism.
Statistical Analysis Plan
Missing data: A complete cases approach will be taken, as it is of interest to predict response and remission in participants who have actually taken an antidepressant for the specified period of time. Therefore, only participants who have valid baseline, week 2 and week 6 (±1) HDRS scores will be selected for the main analyses (or valid week 12 data for the secondary analyses of week 12 outcomes).
Training and validation sample: The data will be randomly divided into an 80% training sample and a 20% validation sample (stratified by treatment group). Model discovery will be done in the training sample, while the predictive performance of the models will be assessed in the validation sample.
研究设计
- 研究类型
- Observational
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Minimum duration of double-blind treatment of 6 weeks
- •Participants must have a valid baseline, 2-week and 6 (±1)- or 12 (±1)-week Hamilton Depression Rating Scale score
- •Aged 18 years or older
- •Participants must have been assigned to either placebo or to an FDA-approved antidepressant
排除标准
- •Inclusion criteria of the trial specify a specific subtype of MDD (e.g. MDD and anxiety; MDD and pain)
研究组 & 干预措施
Antidepressant
The antidepressant group includes participants in eligible clinical trials who have been assigned to antidepressant medication.
干预措施: Antidepressant (Drug)
结局指标
主要结局
Response
时间窗: Week 6
Response is defined as a change of \>=50% on the Hamilton Depression Rating Scale (HDRS, 17-item version) from baseline to week 6 (±1) of the trial.
次要结局
- Remission(Week 12)
- Response(Week 12)
研究者
prof. Peter de Jonge
Professor of Psychiatric Epidemiology
University Medical Center Groningen