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使用分类和回归树模型研究单次低剂量氯胺酮输注的治疗反应:随机安慰剂对照和开放标签试验的事后汇总分析。

Using classification and regression tree modelling to investigate treatment response to a single low-dose ketamine infusion: Post hoc pooled analyses of randomized placebo-controlled and open-label trials.

机构信息

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.

出版信息

J Affect Disord. 2021 Feb 15;281:865-871. doi: 10.1016/j.jad.2020.11.045. Epub 2020 Nov 11.

Abstract

BACKGROUND

Evidence suggests that clinical markers, such as comorbid anxiety, body weight, and others can assist in predicting response to low-dose ketamine infusion in treatment resistant depression patients. However, whether a composite of clinical markers may improve the predicted probability of response is uncertain.

METHODS

The current study investigated the results of our previous randomized placebo-controlled and open-label trials in which 73 patients with treatment-resistant depression (TRD) received a single ketamine infusion of 0.5 mg/kg. Clinical characteristics at baseline, including depression severity, duration of the current episode, obesity, comorbidity of anxiety disorder, and current suicide risk, were assessed as potential predictors in a classification and regression tree model for treatment response to ketamine infusion.

RESULTS

The predicted probability of a composite of age at disease onset, depression severity, duration of current episode, and obesity/overweight was significantly greater (area under curve = .736, p = .001) than that of any one marker (all p > .05). The most powerful predictors of treatment response to ketamine infusion were younger age at disease onset and obesity/overweight. The strongest predictors of treatment nonresponse were longer duration of the current episode and greater depression severity at baseline.

DISCUSSION

Depression severity, duration of the current episode, obesity, and age at disease onset may predict treatment response versus nonresponse to low-dose ketamine infusion. However, whether our predicted probability for a single infusion may be applied to repeated infusions would require further investigation.

CLINICAL TRIAL REGISTRATION

UMIN Clinical Trials Registry (UMIN000023581 and UMIN000016985).

摘要

背景

有证据表明,临床标志物,如合并焦虑症、体重等,可以帮助预测对治疗抵抗性抑郁症患者的低剂量氯胺酮输注的反应。然而,是否将临床标志物组合起来可以提高反应预测的概率尚不确定。

方法

本研究调查了我们之前的随机安慰剂对照和开放标签试验的结果,其中 73 例治疗抵抗性抑郁症(TRD)患者接受了 0.5mg/kg 的单次氯胺酮输注。基线时的临床特征,包括抑郁严重程度、当前发作的持续时间、肥胖、合并焦虑症和当前自杀风险,被评估为氯胺酮输注治疗反应的分类和回归树模型中的潜在预测因子。

结果

疾病发病年龄、抑郁严重程度、当前发作持续时间和肥胖/超重的组合预测概率显著更高(曲线下面积=0.736,p=0.001),而任何一个标志物的预测概率均不高(p>0.05)。对氯胺酮输注治疗反应的最强预测因子是疾病发病年龄较轻和肥胖/超重。对治疗无反应的最强预测因子是当前发作持续时间较长和基线时抑郁严重程度较高。

讨论

抑郁严重程度、当前发作持续时间、肥胖和疾病发病年龄可能预测对低剂量氯胺酮输注的治疗反应与无反应。然而,我们对单次输注的预测概率是否可应用于重复输注还需要进一步研究。

临床试验注册

UMIN 临床试验注册(UMIN000023581 和 UMIN000016985)。

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