CoChat
Sign Up
Cited by 110Pain Management and Placebo EffectLipoproteins and Cardiovascular HealthStatistical Methods in Clinical Trials

Introducing the ‘Drucebo’ effect in statin therapy: a systematic review of studies comparing reported rates of statin‐associated muscle symptoms, under blinded and open‐label conditions

Open access
Penson, Peter E., Mancini, G. B. John, Toth, Peter P., Martin, Seth S., Watts, Gerald F., Sahebkar, Amirhossein, Mikhailidis, Dimitri P., Banach, Maciej +1 more·2018·Journal of Cachexia, Sarcopenia and Muscle
DOI 10.1002/jcsm.12344PMC PMC6240752
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: The ‘placebo effect’ and ‘nocebo effect’ are phenomena whereby beneficial (placebo) or adverse (nocebo) effects result from the expectation that an inert substance will relieve or cause a particular symptom. These terms are often inappropriately applied to effects experienced on drug therapy. Quantifying the magnitude of placebo and nocebo effects in clinical trials is problematic because it requires a ‘no treatment’ arm. To overcome the difficulties associated with measuring the nocebo effect, and the fact that its definition refers to inert compounds, rather than drugs, we introduce the concept of ‘drucebo’ (a combination of DRUg and plaCEBO or noCEBO) to relate to beneficial or adverse effects of a drug, which result from expectation and are not pharmacologically caused by the drug. As an initial application of the concept, we have estimated the contribution of the drucebo effect to statin discontinuation and statin‐induced muscle symptoms by performing a systematic review of randomized controlled trial of statin therapy. Methods: This preferred reporting items for systematic reviews and meta‐analysis‐compliant systematic review was prospectively registered in PROSPERO (CRD42017082700). We searched PubMed and Cochrane Central from inception until 3 January 2018 using a search strategy designed to detect studies including the concepts (Statins AND Placebo AND muscle pain). We included studies that allowed us to quantify the drucebo effect for adverse muscle symptoms of statins by (i) comparing reported rates of muscle symptoms in blinded and unblinded phases of randomized controlled trials and (ii) comparing rates of muscle symptoms at baseline and during blinded therapy in trials that included patients with objectively confirmed statin intolerance at baseline. Extraction was performed by two researchers with disagreements settled by a third reviewer. Results: Five studies allowed the estimation of the drucebo effect. All trials demonstrated an excess of side effects under open‐label conditions. The contribution of the drucebo effect to statin‐associated muscle pain ranged between 38% and 78%. The heterogeneity of study methods, outcomes, and reporting did not allow for quantitative synthesis (meta‐analysis) of the results. Conclusions: The drucebo effect may be useful in evaluating the safety and efficacy of medicines. Diagnosis of the drucebo effect in patients presenting with statin intolerance will allow restoration of life‐prolonging lipid‐lowering therapy. Our study was limited by heterogeneity of included studies and lack of access to individual patient data. Further studies are necessary to better understand risk factors for and clinical management of the drucebo effect.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/jcsm.12344

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A large proportion of symptoms experienced while taking statins is attributable to the expectation of symptoms (the nocebo effect) rather than true pharmacological effects.

    “Current evidence suggests that a large proportion of symptoms when on statins is secondary to the expectation of symptoms rather than true symptoms.”

    From Intolerance upon statin rechallenge: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [6]

    The Results and Conclusions report that a substantial portion of statin-associated muscle pain is attributable to the ‘drucebo’ effect rather than the drug’s pharmacological action. But the review studied muscle symptoms, not all symptoms experienced on statins. Its Conclusions also caution that the measured effect is not a pure measure of expectation: misattribution of pain from other causes can contribute. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • A recent systematic review found that 38% to 78% of individuals reporting statin-associated muscle symptoms also experience symptoms on placebo.

    “Furthermore, a recent systematic review found this occurs in 38% to 78% of individuals reporting statin-associated muscle symptoms [6].”

    From Intolerance upon statin rechallenge: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [6]

    The Abstract (Results; page unavailable) reports that the estimated contribution of the drucebo effect to statin-associated muscle pain ranged from 38% to 78%. It does not report that 38% to 78% of people with statin-associated muscle symptoms experienced symptoms on placebo. In Results (Eligible studies; page unavailable), only 6.9% of participants in one study's placebo run-in reported skeletal muscle symptoms; the study's 78% figure instead concerns estimated statin tolerance or drucebo contribution. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 42 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [19]Banach M, Rizzo M, Toth PP, Farnier M, Davidson MH, Al‐Rasadi K, et al. Statin intolerance—an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch Med Sci 2015; 11(1):1– 23, 1. 25861286 PMC4379380

Cited by

Sorted by citations

Related

Authors
Penson, P. E., Mancini, G. B. J., Toth, P. P., Martin, S. S., Watts, G. F., Sahebkar, A., Mikhailidis, D. P., Banach, M., & on behalf of Lipid and Blood Pressure Meta‐Analysis Collaboration (LBPMC) Group & International Lipid Expert Panel (ILEP)
Affiliations
  • Liverpool John Moores University (GB)
  • University of British Columbia (CA)
  • Johns Hopkins University (US)
  • The University of Western Australia (AU)
  • Mashhad University of Medical Sciences (IR)
  • The Royal Free Hospital (GB)
  • Medical University of Lodz (PL)
Corresponding author
Banach, Maciej
ORCID
Venue
Journal of Cachexia, Sarcopenia and Muscle
Publisher
Wiley
Published
2018-10-11
Volume
9
Issue
6
Pages
1023-1033
ISSN
  • 2190-5991 (ISSN-L)
  • 2190-6009
DOI
10.1002/jcsm.12344
PMC
PMC6240752
OpenAlex
W2902007237
Cited by
110
References
42
Citations by year
2026: 5 · 2025: 6 · 2024: 15 · 2023: 13 · 2022: 17 · 2021: 23 · 2020: 21 · 2019: 9 · 2018: 1
FWCI
1.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Liverpool John Moores University (acceptedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords
nocebo effect, placebo effect, statins, statin intolerance, statin discontinuation, drug safety, expectancy effects, lipid-lowering therapy, randomized controlled trials, blinding, adverse drug reactions, drug efficacy evaluation
MeSH terms
Clinical Trials as Topic, Humans, Muscular Diseases, Risk Factors, Placebo Effect, Publication Bias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Nocebo Effect

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review