Relieving pain using dose-extending placebos: a scoping review

Abstract

Placebos 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 22studies 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. Importantly, provided that nondisclosure is pre-authorized 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.

Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus

“…It is also important to emphasize that these recommendations cannot be generalized in a straightforward manner to non-medical contexts, such as psychotherapy [43]. Several relevant areas, such as the promising field of pharmacological conditioning, or predictors of placebo and nocebo effects, were omitted from the survey because, so far, the relevant evidence is only preliminary [1-14, 44-46]. Finally, we did not focus on specific determinants of placebo and nocebo effects, such as cultural, ethnic, neurobiological or personal characteristics of patients, and the specific ethical and philosophical concerns that these factors raise.…”

Placebo Analgesia in Rodents: Current and Future Research

“…In particular, the ability to create pharmacological memories with behavioral and neurobiological drug-like effects throughout conditioning points to a potential innovative approach to clinical pain management. Combining drugs and placebos in conditioning paradigms (e.g., a dose-extending placebo regimen) is clinically relevant because it may provide us with strategies to optimize clinical outcomes, while dependence, cost, and other unwanted side effects of opioid and nonopioid therapeutics are minimized (Colloca et al, 2016). …”

“…Unlike many other fields of biomedical sciences, the field of placebo analgesia has been led primarily by advances in human research (Colloca & Benedetti, 2005; Colloca, Enck, & DeGrazia, 2016; Wager & Atlas, 2015). Animal studies—that provide critical synergy to human studies—have lagged in this field.…”

Placebos: Honest fakery

“…For example, a doctor might prescribe a blister pack of painkillers, and tell the patient that it contains both drugs and placebos -but not which pills are which. Earlier this year, Colloca and her colleagues reviewed 22 studies that used similar techniques, covering conditions such as insomnia, autoimmune diseases and pain 9 . They concluded that these approaches have the potential to reduce side effects (although some of these may be conditioned responses, too), limit problems with drug dependency and toxicity, and reduce costs.…”