Supplementary Material for: Interactive Motion-Assisted Exposure Therapy for Veterans with Treatment-Resistant Posttraumatic Stress Disorder: A Randomized Controlled Trial

<b><i>Background:</i></b> Veterans with posttraumatic stress disorder (PTSD) tend to benefit less from evidence-based treatments than other PTSD populations. A novel virtual reality and motion-assisted exposure therapy, called 3MDR, provides treatment in an immersive, personalized and activating context. <b><i>Objective:</i></b> To study the efficacy of 3MDR for veterans with treatment-resistant PTSD. <b><i>Method:</i></b> In a randomized controlled trial (<i>n</i> = 43) 3MDR was compared to a non-specific treatment component control group. Primary outcome was clinician-rated PTSD symptoms at baseline, after 3MDR, and at the 12-week and 16-week follow-up (primary end point). Intention-to-treat analyses of covariance and mixed models were applied to study differences between groups at the end point and over the course of intervention, controlling for baseline scores. <b><i>Results:</i></b> The decrease in PTSD symptom severity from baseline to end point was significantly greater for 3MDR as compared to the control group, with a large effect size (<i>F</i>[1, 37] = 6.43, <i>p</i> = 0.016, <i>d</i> = 0.83). No significant between-group difference was detected in the course of PTSD symptoms during treatment when including all time points. The dropout rate was low (7%), and 45% of the patients in the 3MDR group improved clinically. The number needed to treat was 2.86. <b><i>Conclusions:</i></b> In this trial, 3MDR significantly decreased PTSD symptoms in veterans with, on average, a history of 4 unsuccessful treatments. The low dropout rate may be indicative of high engagement. However, a lack of significant differences on secondary outcomes limits conclusions that can be drawn on its efficacy and underlines the need for larger phase III trials. These data show emerging evidence for 3MDR and its potential to progress PTSD treatment for veterans (Dutch Trial Register Identifier: NL5126).

**背景：** 患有创伤后应激障碍（posttraumatic stress disorder, PTSD）的退伍军人，从循证治疗中获益的程度往往低于其他PTSD患者群体。一种名为3MDR的新型虚拟现实辅助运动暴露疗法，可在沉浸式、个性化且具有激活作用的治疗场景中开展治疗。
**目标：** 探究3MDR治疗难治性PTSD退伍军人的疗效。
**方法：** 本研究纳入43例受试者开展随机对照试验，将3MDR组与非特异性治疗成分对照组进行比较。主要结局指标为基线、3MDR治疗结束时、12周及16周随访时临床医师评定的PTSD症状（主要终点）。研究采用意向治疗协方差分析与混合效应模型，在控制基线评分的前提下，比较两组间终点及干预全程的症状差异。
**结果：** 从基线至主要终点，3MDR组PTSD症状严重程度的降幅显著优于对照组，效应量较大（F[1, 37] = 6.43, p = 0.016, d = 0.83）。纳入所有时间点进行分析时，治疗期间两组PTSD症状的变化趋势未发现显著组间差异。本研究脱落率较低（7%），3MDR组45%的受试者实现临床症状改善，需治疗人数（number needed to treat, NNT）为2.86。
**结论：** 本试验中，平均经历过4次失败治疗的难治性PTSD退伍军人接受3MDR治疗后，PTSD症状显著减轻。较低的脱落率提示受试者治疗依从性较高。但次要结局指标未发现显著组间差异，限制了本研究对其疗效的推论，同时也凸显了开展更大样本量III期临床试验的必要性。本研究数据为3MDR及其应用于退伍军人PTSD治疗的潜力提供了初步证据（荷兰试验注册编号：NL5126）。