Coronary artery bypass grafting (CABG) remains one of the most commonly performed cardiac surgeries worldwide. Despite surgical advancements, a significant proportion of patients experience psychological distress following surgery, with depression being particularly common. Current evidence regarding the effectiveness of preoperative psychological interventions in improving postoperative mental health outcomes remains inconclusive. There is a critical need for predictive models that can identify patients at risk of developing clinically significant depressive symptoms (CSDSs) and related psychological conditions after CABG. This multicentre observational study aims to develop and validate prognostic models for predicting CSDSs and other psychological outcomes, including anxiety, post-traumatic stress symptoms and quality of life, 6 weeks after elective CABG surgery.

The study will recruit 300 adult patients undergoing elective CABG (with or without valve intervention) across two Swiss hospitals. Data collected will include demographic, clinical, psychometric, inflammation-related and interoceptive variables. A training set (n=200) will be used to develop predictive models using machine learning, while a held-out test set (n=100) will be used for model validation. The primary outcome prediction will focus on CSDSs, assessed using the Patient Health Questionnaire-9 (PHQ-9), with analyses conducted both categorically (PHQ-9 total score ≥10) and continuously as complementary approaches. Secondary models will address anxiety, using the General Anxiety Disorder Scale-7, post-traumatic stress, using the post-traumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders-5 and health-related quality of life, using the 12-item Short Form Survey. A simplified ‘light solution’ model with fewer predictors will also be developed for broader applicability. This study will address an important gap in perioperative mental healthcare by identifying key predictors of psychological morbidity following CABG, particularly CSDSs. The resulting models may inform future screening and preventive strategies and improve postsurgical outcomes through early identification and intervention in high-risk individuals.

The responsible ethics committee has reviewed and approved this project (Kantonale Ethikkommission Zürich, BASEC number: 2023-02040). The study minimises participant burden by integrating brief validated instruments and limiting psychiatric interviews to relevant outcomes, while ensuring ethical safeguards and respect for participant rights (including written consent). Results will be shared through peer-reviewed publications, conference presentations and stakeholder meetings involving clinicians and mental health professionals. Findings will also be communicated to participating centres and patient communities in accessible formats.

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.