• Luana Colloca, Paul Enck, and David DeGrazia.
• aDepartment of Pain Translational Symptom Science, School of Nursing, University of Maryland, Baltimore, MD, USA bDepartment of Anesthesiology, School of Medicine, University of Maryland, Baltimore, MD, USA cCenter to Advance Chronic Pain Research, University of Maryland, Baltimore, MD, USA dDepartment of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tuebingen, Tuebingen, Germany eDepartment of Bioethics, National Institutes of Health, Bethesda, MD, USA fDepartment of Philosophy, George Washington University, Washington, DC, USA.
• Pain. 2016 Aug 1; 157 (8): 1590-8.

AbstractPlacebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22 studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Provided that nondisclosure is preauthorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated.

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