Supplementary Material for: Experimental approach to inducing anti-histaminergic placebo effects – A randomized controlled trial in healthy volunteers

Introduction: Allergies are an increasingly widespread health problem and prior evidence suggests that psychological factors are involved in their occurrence and alleviation. This study aimed to investigate how placebo treatment can reduce type-I allergic symptoms in a skin prick-test in healthy volunteers.
Methods: Healthy volunteers of all genders were included in the study (N = 88) and were randomized into three groups. i) A classically conditioned group receiving the anti-histaminergic drug cetirizine as unconditioned stimuls (US) and a novel gustatory stimulus as conditioned stimulus (CS), ii) a context-control group receiving cetirizine (US) and water as CS and iii) an open-label placebo group. In the spirit of ethical application of placebo, participants were not blinded with regard to the study question. Histamine skin prick-tests were conducted at baseline, after five acquisition trials, before evocation as well as after three and five evocation trials. Self-rated itch and wheal size measurements served as outcome parameters.
Results: Itch was significantly reduced after medication and (open) placebo intake. Wheal size was only reduced significantly after medication intake during acquisition. After 9 days of wash-out, itch ratings were lower in participants who had received open-label placebo compared to those who had initially received cetirizine. During the evocation week, the decline in wheal size did not reach statistical significance and there was no significant differential effect of group allocation. Reported expectations of symptom relief at the last visit correlated positively with reductions of wheal size.
Conclusion: These results support the theory that treatment expectations correlate with reductions in allergic skin symptoms. Participants of all groups experienced a reduction in itch, while wheal size was only reduced in those participants with high expectations, based on prior experiences and group allocation. Future studies should investigate the underlying neuropsychological mechanisms of these expectation-induced anti-histaminergic effects.

引言：过敏反应已成为日益高发的健康问题，既往研究证据表明心理因素参与其发生与缓解进程。本研究旨在探讨安慰剂治疗如何在健康志愿者的皮肤点刺试验（skin prick-test）中减轻I型过敏性症状（type-I allergic symptoms）。
方法：本研究纳入所有性别的健康志愿者（N=88），并将其随机分为三组。① 经典条件反射组：以抗组胺类药物西替利嗪（cetirizine）作为非条件刺激（unconditioned stimulus, US），以一种新型味觉刺激作为条件刺激（conditioned stimulus, CS）；② 背景对照组：同样给予西替利嗪（US），以清水作为条件刺激（CS）；③ 开放标签安慰剂组。出于安慰剂临床应用的伦理规范，本研究未对受试者隐瞒研究问题。分别于基线、5次习得试验后、唤起试验前，以及3次和5次唤起试验后开展组胺皮肤点刺试验。以自评瘙痒程度与风团大小作为结局评价指标。
结果：用药及（开放标签）安慰剂摄入后，受试者的瘙痒症状均显著减轻。风团大小仅在习得阶段用药后出现显著缩小。经过9天洗脱期后，初始接受开放标签安慰剂的受试者瘙痒评分，低于初始接受西替利嗪的受试者。在唤起试验周期间，风团大小的缩小未达到统计学显著性，且各组间无显著差异效应。末次随访时报告的症状缓解预期与风团大小的缩小呈正相关。
结论：本研究结果支持“治疗预期与变态反应性皮肤症状减轻相关”这一理论。所有组别受试者均出现瘙痒症状减轻，而风团大小仅在那些基于既往体验与分组具有高预期的受试者中出现缩小。未来研究应进一步探讨此类由预期介导的抗组胺效应背后的神经心理机制。