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Placebo and nocebo in clinical practice: An online cross-sectional survey of healthcare professionals from European countries on views, practices and training needs

by Mary O’Keeffe, Nathan Skidmore, Arianna Bagnis, Przemysław Bąbel, Elżbieta A. Bajcar, Alessandra De Palma, Andrea W.M. Evers, Eveliina Glogan, Julia W. Haas, Stefanie H. Meeuwis, Marek Oleszczyk, Antonio Portolés, Johan W.S. Vlaeyen, Katia Mattarozzi, on behalf of PANACEA Consortium

Background

Placebo and nocebo effects significantly influence health outcomes, yet healthcare professionals receive limited training and guidance on their mechanisms and clinical application, creating a gap in education and practical understanding. Conducted within the European PANACEA Consortium, this study evaluated healthcare professionals’ knowledge, attitudes, and practices regarding placebo and nocebo effects, and assessed their needs in further education.

Methods

An online cross-sectional survey among a European multi-country convenience sample of healthcare professionals collected data assessing participants’ knowledge, perceptions, and experiences regarding placebo and nocebo effects; their application and ethical considerations in clinical practice; and investigated educational needs and interest in further training. Quantitative data were analyzed using descriptive statistics, and thematic analysis was applied to the free-text responses.

Results

Amongst 807 participants, 71.7% reported taking advantage of placebo effects in their practice, and over half of participants (55.8%) observing nocebo effects. Participants reported feeling somewhat confident (53.3%) in harnessing placebo effects with 47.5% feeling confident in preventing nocebo effects. The majority of respondents had not received formal training on placebo and nocebo effects, with most expressing an interest in further training in areas such as healthcare education, emphasizing communication skills to enhance placebo effects, and knowledge to recognize and reduce nocebo effects.

Conclusions

There is a significant need for more comprehensive training on placebo and nocebo effects, particularly in early health professional education. These findings informed the development of educational resources and best practice recommendations developed as part of the outcomes from the PANACEA Consortium, improving the understanding and application of these effects among healthcare professionals across Europe.

Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis

Por: Türkmen · C. · Sacu · S. · Furukawa · Y. · de Cates · A. N. · Schoevers · R. A. · Kamphuis · J. · Chevance · A. · Weisz · J. R. · Emslie · G. J. · Strawn · J. R. · Hetrick · S. E. · Efthimiou · O. · Salanti · G. · van Dalfsen · J. H. · Furukawa · T. A. · Cipriani · A.
Introduction

Major depressive disorder (MDD) is among the most common psychiatric disorders in children and adolescents. While previous meta-analyses have synthesised evidence on the efficacy and acceptability of newer-generation antidepressants in this population, specific adverse events (AEs) remain poorly characterised. This is of high clinical importance, as AEs are burdensome for patients, can reduce treatment adherence and lead to discontinuation. Here, we present a protocol for a network meta-analysis designed to evaluate the specific AE profile and comparative tolerability of newer-generation antidepressants in children and adolescents with MDD.

Methods and analysis

The planned study will include double-blind randomised controlled trials that compared one active drug with another and/or placebo for the acute treatment of MDD in children and adolescents. The following antidepressants will be considered: agomelatine, alaproclate, bupropion, citalopram, desvenlafaxine, duloxetine, edivoxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, vilazodone and vortioxetine. The primary outcomes will include the number of patients experiencing at least one AE, specific non-serious AEs, serious AEs (eg, suicidal ideation) and AEs leading to treatment discontinuation. Published and unpublished studies will be retrieved through a systematic search in the following databases: PubMed, Embase, Cochrane Library (including the Cochrane Central Register of Controlled Trials), Web of Science Core Collection, PsycInfo and regulatory agencies’ registries. Study selection and data extraction will be performed independently by two reviewers. For each outcome, a network meta-analysis will be performed to synthesise all evidence. Consistency will be assessed through local and global methods, and the confidence in the evidence will be evaluated using the Confidence in Network Meta-Analysis web application. All analyses will be conducted in the R software.

Ethics and dissemination

The planned review does not require ethical approval. The findings will be published in a peer-reviewed journal and may be presented at international conferences.

PROSPERO registration number

CRD420251011399.

Estimating the economic and societal burden of suicide and suicide attempts in India: a study protocol

Por: Jain · N. · Wijnen · B. · Lohumi · I. · Madan · J. · Evers · S.
Introduction

Suicide has a substantial economic burden, yet in low- or middle-income countries, the analysis is constrained by the absence of disaggregated economic data. Existing studies primarily rely on gross costing methods, overlooking sector-specific costs such as healthcare, law enforcement and productivity losses at the family and community levels. Furthermore, the societal perspective, essential for understanding the multifaceted economic impacts of suicide, remains insufficiently explored in the Indian context.

Methods and analysis

This study will quantify the economic burden of suicide and suicide attempts in India. The initial phase will involve developing a resource-use measure instrument to capture the societal costs associated with suicide. Subsequently, a retrospective, incidence-based study will be conducted in India using the developed instrument. This will also be complemented with the Health-Related Quality of Life Assessment using EuroQOL (EQ-5D-5L). Exploratory subgroup cost comparisons (eg, suicide methods, healthcare facility type) will use non-parametric tests, including the Mann–Whitney U and Kruskal–Wallis tests. Generalised linear mixed models (gamma distribution and log link) will analyse longitudinal cost and HRQoL data, besides bootstrapping techniques and sensitivity analyses.

Ethics and dissemination

Ethics approval was obtained for the study from the institutional review board of the Indian Law Society (ILS/141/2024). All data collected during the study will adhere to ethical guidelines, taking informed consent. The findings of the study will be disseminated through peer-reviewed journals to aid data-driven decision-making.

Trial registration

Clinical Trial Registry of India (CTRI/2025/02/080380), date of registration: 12/02/2025.

Evidence map of oesophageal surgery: protocol for a living systematic review and meta-analysis

Por: Benignus · C. · Schiedeck · T. · Avramovska · I. · Evers · L. M. · Giulini · L. · Heger · P. · Diener · M. K. · Hüttner · F. J.
Introduction

Surgery represents the cornerstone for the treatment of several benign and malignant oesophageal disorders. Yet synthesising the growing body of evidence from clinical research is becoming increasingly challenging. Evidence mapping with living systematic reviews (SRs) and living meta-analyses offers a structured, continuously updated approach to navigating emerging data. This study aims to provide a real-time, interactive resource to support evidence-based decision-making for oesophageal surgery.

Methods and analysis

This study follows PRISMA guidelines and uses the EVIglance Studio web application to develop a living evidence map in oesophageal surgery. A systematic literature search will be conducted across the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and MEDLINE (PubMed) to identify randomised controlled trials (RCTs) and SRs related to oesophageal surgery, without any date or language restrictions. Study selection and data extraction will be performed independently by two reviewers. Key clinical and surgical outcomes, including morbidity, mortality, quality of life and oncological endpoints, will be extracted. Risk of bias in RCTs will be assessed using the Cochrane Risk of Bias 2.0 tool, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system will be applied to evaluate the certainty of evidence. If at least three randomised trials address the same research question, a living meta-analysis will be conducted using random-effects models. The evidence map will be updated at least every 6 months.

Ethics and dissemination

This study does not involve individual patient data or any private information. Therefore, ethical approval is not required. As it uses only publicly available data, this study design qualifies as exempt from institutional review. The resulting evidence map is designed to support fast and structured access to high-quality surgical data - an approach not yet available in oesophageal surgery. The tool is expected to aid patients, clinicians and researchers alike by improving access to reliable information, supporting clinical decision-making and highlighting gaps in current evidence. On completion, results will be published in an open-access format and made permanently accessible via www.evidencemap.surgery, with continuous updates.

PROSPERO registration number

CRD420251022736 (https://www.crd.york.ac.uk/prospero/)

The Economic and societal burden associated with drug-resistant epilepsy in the Netherlands: an AIM@EPILEPSY burden-of-disease study protocol

Por: Elabbasy · D. · Evers · S. · Majoie · M. H. J. M. · Schijns · O. E. M. G. · MRabet · L. · van Kranen-Mastenbroek · V. H. J. M. · Eekers · D. B. P. · Houben · R. · Hendriks · M. · Colon · A. · van Mastrigt · G. A. P. G.
Background

Living with epilepsy, especially drug-resistant epilepsy (DRE), imposes several challenges for people diagnosed with the condition. These challenges include the physical and mental implications of epilepsy on both caregivers and patients with epilepsy. For the more than 120 000 individuals living with this neurological disorder in the Netherlands, along with their families, daily activities become hazardous, limited and costly, significantly affecting their health-related quality of life (HRQoL). As data on the burden of epilepsy in the Netherlands are lacking, studies attempting to capture the impact of epilepsy on individuals, caregivers and society are needed to enhance understanding and help address the burden of epileptic seizures.

Methods and analysis

The study is part of the AIM@EPILEPSY project. The project aims to develop a planning suite enabling cost-saving, minimally invasive treatment for epilepsy. By surveying 330 people with epilepsy and an anticipated sample of 150–200 informal caregivers across the Netherlands, using standardised questionnaires focusing on associated societal costs and the impact on HRQoL, this bottom-up, prevalence-based prospective study aims to understand the societal burden of DRE in the Netherlands. The data will be collected at 0, 3, 6 and 12 months of follow-up. The study results will describe the economic impact of epilepsy, focusing on cost-of-illness () and HRQoL (utilities) in the Netherlands.

Ethics and dissemination 

The proposed study was approved by the Maastricht University Medical Ethics Review Committee (Approval reference: FHML-REC/2024/067/Amendment/2024_16). The result of the study is planned to be published in a peer-reviewed journal and presented at international and local scientific conferences.

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