Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden2Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
JAMA Psychiatry. 2017 May 1;74(5):501-510. doi: 10.1001/jamapsychiatry.2016.3955.
Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear.
To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables.
PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked.
Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder.
Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies.
Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes.
D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.
目前尚不清楚 D-环丝氨酸（DCS）是否以及在何种条件下能增强暴露为基础的认知行为疗法对焦虑、强迫症和创伤后应激障碍的疗效。
明确 DCS 是否优于安慰剂增强焦虑、强迫症和创伤后应激障碍的认知行为疗法疗效，并评估抗抑郁药是否与 DCS 相互作用以及潜在调节变量的作用。
从建库至 2016 年 2 月 10 日，检索了 PubMed、EMBASE 和 PsycINFO 数据库。还查阅了先前综述和荟萃分析的参考文献列表以及随机临床试验报告。
如果研究为（1）DCS 作为暴露为基础的认知行为疗法增强策略的双盲随机临床试验，以及（2）入组的研究对象为特定恐惧症、社交焦虑症、伴有或不伴有广场恐怖症的惊恐障碍、强迫症或创伤后应激障碍的患者，则纳入研究。
从作者处获取原始数据并进行质量控制。对数据进行分级以确保研究之间具有一致的指标（评分范围为 0-100）。我们使用了 3 级多层模型，对参与者内的结局进行重复测量，参与者内嵌套研究。
22 项符合条件的试验中有 21 项获得了个体参与者数据，共纳入了 1073 名符合条件的参与者中的 1047 名。在控制抗抑郁药使用的情况下，接受 DCS 的参与者在治疗前至治疗后的改善更为明显（平均差值，-3.62；95%CI，-0.81 至-6.43；P=0.01；d=-0.25），但在治疗前至治疗中期（平均差值，-1.66；95%CI，-4.92 至 1.60；P=0.32；d=-0.14）或治疗前至随访（平均差值，-2.98，95%CI，-5.99 至 0.03；P=0.05；d=-0.19）的改善不明显。进一步的分析表明，与安慰剂组相比，接受 DCS 治疗的参与者在治疗后和随访时的症状严重程度更低。抗抑郁药未调节 DCS 的作用。没有一个预先指定的患者或研究水平的调节因素与结局相关。
D-环丝氨酸与暴露为基础的治疗有轻度增强作用。这种作用不受同时使用抗抑郁药的影响。需要进一步研究以确定与 DCS 反应相关的患者和/或治疗特征。
