Larsen, Heldbo Reines, H. Lundbeck A/S, Copenhagen Valby, Denmark. Kennedy, Centre for Depression and Suicide Studies, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. Thase, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Psychopharmacol Bull. 2020 Sep 14;50(4):8-28.
To investigate whether the efficacy of antidepressants can be understood in terms of patient response-trajectory classes.
Patient-level data were analysed from 1357 adults with MDD randomised to either escitalopram 20 mg/day ( = 676) or placebo ( = 681) in five 8-week randomised placebo-controlled trials. Growth mixture models (GMMs) were used to identify the response trajectories; longitudinal latent class analysis (LLCA) was used to corroborate the findings.
Three classes of response were identified for escitalopram and placebo based on the trajectory of the patients' Montgomery-Åsberg Depression Rating Scale (MADRS) total scores during treatment. All three classes had similar mean baseline MADRS scores, but the change from baseline after 8 weeks differed: -4.2 MADRS points for non-responders, -18.4 MADRS points for slow responders, and -26.7 points for fast responders. The proportions of non-responders, slow responders and fast responders were 53%, 38% and 9%, respectively, with placebo and 27%, 58% and 14%, respectively, with escitalopram. Receiver operating curve analysis showed that a cut-off of ≥43% improvement from baseline to week 2 predicted fast responders, and a cut-off of ≥28% improvement from baseline to week 4 predicted responders (fast or slow). There were no clinically useful differences at baseline that predicted the trajectory class to which a patient would belong.
The presence of fast-, slow- and non-responder classes has a clear clinical relevance for guiding treatment decisions; individual patients can be classified by the change in their MADRS score from baseline at 2 or 4 weeks.
探讨抗抑郁药的疗效是否可以根据患者的反应轨迹类别来理解。
对 1357 名 MDD 成年患者进行了患者水平数据分析,这些患者随机分为依西酞普兰 20mg/天(n=676)或安慰剂(n=681),进行了五项为期 8 周的随机安慰剂对照试验。采用增长混合模型(GMM)来识别反应轨迹;采用纵向潜在类别分析(LLCA)来证实这些发现。
根据治疗期间患者的蒙哥马利-阿斯伯格抑郁评定量表(MADRS)总分的轨迹,确定了依西酞普兰和安慰剂的三种反应类别。所有三种类别都有相似的平均基线 MADRS 评分,但 8 周后从基线的变化不同:无反应者为 -4.2 MADRS 点,慢反应者为 -18.4 MADRS 点,快反应者为 -26.7 点。无反应者、慢反应者和快反应者的比例分别为安慰剂组 53%、38%和 9%,依西酞普兰组分别为 27%、58%和 14%。受试者工作特征曲线分析显示,从基线到第 2 周改善≥43%可预测快反应者,从基线到第 4 周改善≥28%可预测反应者(快或慢)。基线没有可预测患者所属轨迹类别的临床有用差异。
快反应者、慢反应者和无反应者类别的存在对指导治疗决策具有明确的临床意义;可以根据患者从基线到第 2 或 4 周时 MADRS 评分的变化对患者进行分类。