{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:27:15Z","timestamp":1792290435305,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The \u2018placebo effect\u2019 and \u2018nocebo effect\u2019 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 \u2018no treatment\u2019 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 \u2018drucebo\u2019 (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\u2010induced muscle symptoms by performing a systematic review of randomized controlled trial of statin therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This preferred reporting items for systematic reviews and meta\u2010analysis\u2010compliant 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five studies allowed the estimation of the drucebo effect. All trials demonstrated an excess of side effects under open\u2010label conditions. The contribution of the drucebo effect to statin\u2010associated muscle pain ranged between 38% and 78%. The heterogeneity of study methods, outcomes, and reporting did not allow for quantitative synthesis (meta\u2010analysis) of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u2010prolonging lipid\u2010lowering 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12344","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T03:34:16Z","timestamp":1539315256000},"page":"1023-1033","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Introducing the \u2018Drucebo\u2019 effect in statin therapy: a systematic review of studies comparing reported rates of statin\u2010associated muscle symptoms, under blinded and open\u2010label conditions"],"prefix":"10.1002","volume":"9","author":[{"given":"Peter E.","family":"Penson","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences Liverpool John Moores University  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. B. John","family":"Mancini","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Toth","sequence":"additional","affiliation":[{"name":"Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Division of Cardiology, Department of Medicine Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth S.","family":"Martin","sequence":"additional","affiliation":[{"name":"Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Division of Cardiology, Department of Medicine Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald F.","family":"Watts","sequence":"additional","affiliation":[{"name":"Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology The University of Western Australia  Perth WA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"Neurogenic Inflammation Research Center Mashhad University of Medical Sciences  Mashhad Iran"},{"name":"School of Pharmacy Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri P.","family":"Mikhailidis","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Royal Free Hospital Campus University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-6874","authenticated-orcid":false,"given":"Maciej","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Hypertension, Chair of Nephrology and Hypertension Medical University of Lodz  Lodz Poland"},{"name":"Polish Mother's Memorial Hospital Research Institute (PMMHRI)  Lodz Poland"},{"name":"Cardiovascular Research Centre University of Zielona Gora  Zielona Gora Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of Lipid and Blood Pressure Meta\u2010Analysis Collaboration (LBPMC) Group & International Lipid Expert Panel (ILEP)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,11]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"203","article-title":"The nocebo reaction","volume":"95","author":"Kennedy 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