Evidence map›Paper›PMID 30146056›Full record

ArticleInternational review of neurobiology2018

Placebo and Active Treatment Additivity in Placebo Analgesia: Research to Date and Future Directions.

Matthew J Coleshill, Louise Sharpe, Luana Colloca, Robert Zachariae, Ben Colagiuri

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International review of neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 4 pooled it
2.8field-weighted citation impact, top 9% of its field
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

15 citing papers in PubMed, 4 syntheses or guidelines pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Pain, mindfulness, and placebo: a systematic review.Frontiers in integrative neuroscience · 2024
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. Placebo-response inflation in supportive oncology symptom trials: mechanisms, methodological challenges, and design implications.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026
    Review
  9. Contextual effects: how to, and how not to, quantify them.BMC medical research methodology · 2024
    Review
  10. Review
  11. Review
  12. Article
  13. Placebo From an Enactive Perspective.Frontiers in psychology · 2021
    Article
  14. Article
  15. Article
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

5 authors at 4 institutions in 3 countries.

Matthew J ColeshillSchool of Psychology, University of Sydney, Sydney, NSW, Australia; St Vincent's Clinical School, St Vincent's Hospital, University of New South Wales, Sydney, NSW, Australia; Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, NSW, Australia. Electronic address: m.coleshill@unsw.edu.au.
Louise SharpeSchool of Psychology, University of Sydney, Sydney, NSW, Australia.
Luana CollocaCenter to Advance Chronic Pain Research, University of Maryland, Baltimore, MD, United States; School of Nursing, University of Maryland, Baltimore, MD, United States; School of Medicine, University of Maryland, Baltimore, MD, United States.
Robert ZachariaeAarhus University Hospital and Department of Psychology and Behavioural Science, Aarhus University, Aarhus, Denmark.
Ben ColagiuriSchool of Psychology, University of Sydney, Sydney, NSW, Australia.
University of Sydney · AUAarhus University Hospital · DKSt Vincent's Clinic · AUUniversity of Maryland, Baltimore · US

Funding

Chronic orofacial pain: genetics, cognitive-emotional factors, and endogenous modulatory systemsR01DE025946 · NIDCR · UNIVERSITY OF MARYLAND BALTIMORE · PI COLLOCA, LUANA · 2016 to 2019
$2.1M
NIDCR NIH HHS R01 DE025946
6 · The paper itself

Abstract

Placebo analgesia is a robust experimental and clinical phenomenon. While our understanding of the mechanisms of placebo analgesia has developed rapidly, some central questions remain unanswered. Among the important questions is how placebo analgesia interacts with active analgesic effects. It is an assumption underlying double-blind randomized placebo-controlled trials (RCTs) that the true effect of a treatment can be determined by examining the effect of the active treatment arm and subtracting the response in the placebo group ("the assumption of additivity"). However, despite the importance of this assumption for the interpretation of RCTs, it has rarely been formally examined. This article reviews the assumption of additivity in placebo analgesia by examining studies employing factorial designs manipulating both the receipt of an active analgesic and instructions about the treatment being delivered. In reviewing the literature, we identified seven studies that allowed a test of additivity. Of these, four found evidence against additivity, while the remaining three studies found results consistent with additivity. While the limited available data are somewhat mixed, the evidence suggests that at least under some conditions the assumption of additivity does not hold in placebo analgesia. The concordance between mechanisms of the active analgesic and placebo analgesia may influence whether additivity occurs or not. However, more research using factorial designs is needed to disentangle the relationship between placebo analgesia and the active effect of analgesic treatments.

Indexed as

Biomedical ResearchPlacebo EffectAnalgesiaHumansPainAdditivityDrug interactionExpectancyPainPlacebo analgesiaPlacebo effectRandomized controlled trials

Identifiers

PMID30146056
PMCPMC6179351
OpenAlexW2887110406

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.