The impact of pharmaceutical form and simulated side effects in an open-label-placebo RCT for improving psychological distress in highly stressed students (Open Data and Open Materials)

Open-label placebo (OLP) may be utilized to reduce psychological distress. Yet, potential contextual effects have not been explored. We investigated the impact of pharmaceutical form and the simulation of side effects in a parallel group RCT (DRKS00030987). A sample of 177 highly stressed university students at risk of depression were randomly assigned by computer generated tables to a one-week intervention with active or passive OLP nasal spray or passive OLP capsule or a no-treatment control group. After the intervention, groups differed significantly in depressive symptoms but not regarding other outcomes of psychological distress (stress, anxiety, sleep quality, somatization), well-being or treatment expectation. OLP groups benefitted significantly more compared to the no-treatment control group (<em>d</em>=.40), OLP nasal spray groups significantly more than the OLP capsule group (<em>d</em>=.40) and the active OLP group significantly more than the passive OLP groups (<em>d</em>=.42). Interestingly, before intervention, most participants, regardless of group assignment, believed that the OLP capsule would be most beneficial. The effectiveness of OLP treatments seems to be highly influenced by the symptom focus conveyed by the OLP rationale. Moreover, pharmaceutical form and simulation of side effects may modulate efficacy, while explicit treatment expectation seems to play a minor role.开放标签安慰剂（Open-label Placebo, OLP）可用于缓解心理痛苦，但其潜在的情境效应尚未得到探索。本研究针对平行组随机对照试验（DRKS00030987），探究了药物剂型与副作用模拟对其疗效的影响。研究招募了177名存在抑郁风险且处于高应激状态的大学生，通过计算机生成的随机数字表将其随机分配至四组：为期一周的活性或非活性开放标签安慰剂鼻喷剂干预组、非活性开放标签安慰剂胶囊干预组，以及无治疗对照组。干预结束后，各组在抑郁症状上存在显著差异，但在其他心理痛苦相关结局（应激、焦虑、睡眠质量、躯体化）、幸福感或治疗期待上并无显著差异。与无治疗对照组相比，开放标签安慰剂组的获益显著更高（效应量*d*=0.40）；开放标签安慰剂鼻喷剂组的获益显著高于安慰剂胶囊组（*d*=0.40）；活性开放标签安慰剂组的获益显著高于非活性开放标签安慰剂组（*d*=0.42）。值得注意的是，干预前，无论被分配至哪一组，绝大多数参与者均认为安慰剂胶囊的获益效果最优。开放标签安慰剂治疗的有效性似乎极大程度上受其治疗原理所传递的症状关注点的影响。此外，药物剂型与副作用模拟或可调节治疗疗效，而明确的治疗期待对疗效的影响相对较小。