Placebos Without Deception: Outcomes, Mechanisms, and Ethics

Abstract

Scientific research indicates that open-label and dose-extending placebos (that patients know are placebos) can elicit behavioral, biological, and clinical outcome changes. In this chapter, we present the state-of-the-art evidence and ethical considerations about open-label and dose-extending placebos, discussing the perspective of giving placebos with a rational, as dose extension of active drugs, or expectancy boosters. Previous comprehensive reviews of placebo use have considered how to harness placebo effects in medicine and the need to focus on elements of the clinical encounter as well as patient–clinician relations. Here, we illustrate the similarities and differences between standard (deceptive) placebos, open-label placebos and dose-extending placebos. We conclude that placebos without deception would override ethical barriers to their clinical use. This paves the way to future large-scale, pragmatic randomized trials that investigate the potential of ethical open-label and dose-extending placebos to improve patients’ outcomes, and reduce side effects.

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

“…However, more research is needed in other conditions and patient groups before recommendations can be developed about their possible use in clinical practice. For example, non-significant findings were found in a pilot study in patients with a major depressive disorder in a small sample of 12 patients, although the medium effect size was comparable to the other trials [32-34]. It has to be established whether specific patient groups or subgroups of patients benefit more than others from open-label placebos, or whether biological or psychological markers are associated with the effectiveness of these open-label placebo strategies.…”

“…It has to be established whether specific patient groups or subgroups of patients benefit more than others from open-label placebos, or whether biological or psychological markers are associated with the effectiveness of these open-label placebo strategies. Promising is the case of dose-extending placebos (e.g., placebo given along with active medication) that mimic the psychobiological responses that are associated with the effectiveness of the medications with the potential of reducing side effects and costs [32]. Although prescription of placebos is not yet regulated in any part of the world and additional research is necessary on its short- and long-term effects, open-label prescription of placebos could be considered as a possible future watch and wait strategy or for use in long-term conditions when other treatment options have failed [33].…”

Preface

“…These findings are among the first attempts to outline the clinical relevance of shaping patients’ expectancies (Darnall & Colloca, 2018; Klinger, Stuhlreyer, Schwartz, Schmitz, & Colloca, 2018) and to use dose-extending placebos along with pharmacological conditioning as a potential pain management tool to taper opioids (Colloca, Enck, & DeGrazia, 2016; Colloca & Howick, 2018). …”

Clinical Use of Placebo Effects in Patients With Pain Disorders

“…For clinical applications, it is important to know that placebo research yielded ethical possibilities to use placebo effects without deception and without the use of placebos (c.f. Colloca & Howick, 2018). In other words, the placebo effect can be achieved without inert substances (i.e., placebos) or deception.…”