Carratta Katja, Bodonyi Kiara, Frey Nascimento Antje, Friis Daniel, von Känel Roland, Bircher Lukas, Koechlin Helen, Bernstein Michael, Streitberger Konrad, Arnet Isabelle, Roth Alfred Josef, Ronel Joram, Olliges Elisabeth, Locher Cosima
Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, Zürich, Switzerland.
Division of Clinical Psychology and Psychotherapy, Faculty of Psychology, University of Basel, Basel, Switzerland.
BMJ Open. 2025 May 24;15(5):e098253. doi: 10.1136/bmjopen-2024-098253.
Chronic non-cancer pain presents a global health problem, with a significant increase in opioid prescriptions over recent decades. However, opioid therapy poses risks of adverse events, overdose and non-medical use. As a result, many patients seek to discontinue or reduce their opioid intake. Strategies for opioid tapering often lack efficacy, prompting the investigation of novel approaches like open-label placebo (OLP), that is, the administration of a placebo with full disclosure that it is a placebo. OLP has shown efficacy in chronic non-cancer pain syndromes and has been suggested as a promising candidate for medication tapering. This study aims to assess whether OLPs can enhance the reduction of daily morphine equivalent dose (MED) in chronic non-cancer pain patients and examines its potential in mitigating opioid withdrawal symptoms.
This study is designed as a randomised, controlled, single-centre trial. Participants will be randomised into either an OLP group or a control group. The study duration will span six to nine weeks, during which all participants will aim to reduce their opioid intake. Both groups will monitor their opioid intake daily using a diary app and will receive feedback on their progress of reducing opioids. Additionally, participants in the OLP group will receive OLP tablets for the entire study period. During the first week, the OLP group will undergo a one week learning phase using a classical conditioning paradigm, where each opioid intake is paired with a placebo. In the subsequent five weeks, the OLP group will enter a dose-extension phase in which only the first opioid intake of the day is paired with a placebo, and additional placebos can be taken as desired. At the end of the study, qualitative interviews will be conducted with the first 15 participants in the OLP group. The primary outcome measure is daily opioid intake. Secondary outcomes include opioid withdrawal symptoms, pain severity, disability, anxiety, depression, opioid beliefs, intervention expectancy and qualitative data. Statistical analyses will include analysis of covariance and regression models.
The ethics committee of the Canton of Zurich, Switzerland, approved the study (SNCTP-nr.: SNCTP000005853/BASEC nr.: 2023-02327).Participants will be compensated with 100 Swiss Francs for their full participation in the study. Participants who will take part in the qualitative interview will be compensated with additional 15 Swiss Francs.
This study is registered at clinicaltrials.gov: NCT06350786.
慢性非癌性疼痛是一个全球性的健康问题，近几十年来阿片类药物的处方量显著增加。然而，阿片类药物治疗存在不良事件、过量使用和非医疗用途的风险。因此，许多患者寻求停止或减少阿片类药物的摄入量。阿片类药物减量策略往往缺乏疗效，这促使人们研究新的方法，如开放标签安慰剂（OLP），即完全公开其为安慰剂的情况下给予安慰剂。OLP已在慢性非癌性疼痛综合征中显示出疗效，并被认为是药物减量的一个有前景的候选方法。本研究旨在评估OLP是否能增强慢性非癌性疼痛患者每日吗啡当量剂量（MED）的减少，并研究其在减轻阿片类药物戒断症状方面的潜力。
本研究设计为一项随机、对照、单中心试验。参与者将被随机分为OLP组或对照组。研究持续时间为六至九周，在此期间所有参与者的目标是减少阿片类药物的摄入量。两组都将使用日记应用程序每日监测阿片类药物的摄入量，并将收到关于其减少阿片类药物进展的反馈。此外，OLP组的参与者在整个研究期间将服用OLP片剂。在第一周，OLP组将使用经典条件反射范式进行为期一周的学习阶段，每次阿片类药物摄入都与安慰剂配对。在随后的五周内，OLP组将进入剂量扩展阶段，在此阶段仅将当天的第一次阿片类药物摄入与安慰剂配对，并且可以根据需要服用额外的安慰剂。在研究结束时，将对OLP组的前15名参与者进行定性访谈。主要结局指标是每日阿片类药物摄入量。次要结局包括阿片类药物戒断症状、疼痛严重程度、残疾、焦虑、抑郁、阿片类药物信念、干预预期和定性数据。统计分析将包括协方差分析和回归模型。
瑞士苏黎世州伦理委员会批准了该研究（SNCTP编号：SNCTP000005853/BASEC编号：2023 - 02327）。参与者若全程参与研究将获得100瑞士法郎的补偿。参与定性访谈的参与者将额外获得15瑞士法郎的补偿。
本研究已在clinicaltrials.gov注册：NCT06350786。
