Evidence map›Paper›PMID 40754523›Full record

Trial reportBMC medicine2025

Placebo effects improve sickness symptoms and drug efficacy during systemic inflammation: a randomized controlled trial in human experimental endotoxemia.

Justine Schmidt, Johanna Reinold, Hana Rohn, Manfred Schedlowski, Harald Engler, Sigrid Elsenbruch, Sven Benson

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Justine SchmidtInstitute for Medical Education, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.
Johanna ReinoldInstitute for Medical Education, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.
Hana RohnDepartment of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.
Manfred SchedlowskiInstitute of Medical Psychology and Behavioral Immunobiology, C-TNBS, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.
Harald EnglerInstitute of Medical Psychology and Behavioral Immunobiology, C-TNBS, University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany.
Sigrid ElsenbruchDepartment of Medical Psychology and Medical Sociology, Faculty of Medicine, Ruhr University Bochum, Bochum, 44901, Germany.
Sven BensonInstitute for Medical Education, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, Essen, 45122, Germany. sven.benson@uk-essen.de.

Funding

Deutsche Forschungsgemeinschaft 422744262-TRR 289
6 · The paper itself

Abstract

backgroundSystemic inflammation triggers a wide range of sickness symptoms, including bodily discomfort and affective symptoms, which are relevant to numerous health conditions. While extensive research in the placebo field demonstrates that positive expectations can improve symptoms, it remains unclear if interventions designed to augment positive treatment expectations can alleviate sickness symptoms in the context of immunomodulatory drug therapies.

methodsIn this randomized, controlled, fully balanced 2 × 2 factorial placebo design, N = 124 healthy volunteers received either active ibuprofen treatment (600 mg per os) or placebo, combined with either a positive or neutral labeling of the treatment by the physician. All participants were intravenously injected with lipopolysaccharide (LPS, 0.8 ng per kg of body weight) as a translational model of inflammation-induced sickness symptoms. Primary outcomes were bodily and affective symptoms, assessed at baseline and up to 6 h after injection, along with a range of inflammatory markers.

resultsIbuprofen substantially alleviated inflammation-induced symptoms. Positive labeling also improved bodily and affective symptoms of sickness, even in placebo-treated groups. Notably, positive labeling enhanced ibuprofen's efficacy for alleviating affective symptoms, supporting that expectations can boost the efficacy of a highly effective anti-inflammatory treatment. However, labeling did not influence changes in physiological markers of inflammation, suggesting that the effects of expectations primarily act through mechanisms distinct from direct modulation of peripheral immune responses.

conclusionsPlacebo mechanisms engaged by physician communication can independently alleviate inflammation-induced symptom burden and enhance the efficacy of an anti-inflammatory medication. Results underscore the critical role of healthcare provider communication and pave the way for improved treatment strategies for conditions characterized by inflammation-driven symptoms.

trial registrationDRKS00023088, registration website German Clinical Trials Register (date registered: 10/22/2020).

Indexed as

Anti-Inflammatory Agents, Non-SteroidalEndotoxemiaIbuprofenInflammationPlacebo EffectAdultFemaleHealthy VolunteersHumansLipopolysaccharidesMaleMiddle AgedYoung AdultAnti-Inflammatory Agents, Non-SteroidalIbuprofenLipopolysaccharidesAnxietyBalanced placebo designDepressionEndotoxemiaExpectationsIbuprofenInflammationLipopolysaccharidePlacebo effectSickness behaviour

Identifiers

PMID40754523
PMCPMC12320331

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.