The downside to choice: instrumental control increases conditioned nocebo hyperalgesia.

ABSTRACT: Nocebo hyperalgesia is a pervasive problem in which the treatment context triggers negative expectations that exacerbate pain. Thus, developing ethical strategies to mitigate nocebo hyperalgesia is crucial. Emerging research suggests that choice has the capacity to reduce nocebo side effects, but choice effects on nocebo hyperalgesia have not been explored. This study investigated the impact of choice on conditioned nocebo hyperalgesia using a well-established electrocutaneous pain paradigm where increases in noxious stimulation were surreptitiously paired with the activation of a sham device. In study 1, healthy volunteers (N = 104) were randomised to choice over (nocebo) treatment administration, nocebo administration without choice, or a natural history control group. Nocebo hyperalgesia was greater for those with choice than no choice, suggesting that choice increased rather than diminished nocebo hyperalgesia. Study 2 tested whether providing positive information about the benefits of choice in coping with pain could counteract heightened nocebo hyperalgesia caused by choice. A different sample of healthy adults (N = 137) were randomised to receive nocebo treatment with choice and positive choice information, choice only, or no choice. The positive choice information failed to attenuate the effect of choice on nocebo hyperalgesia. The current results suggest that, rather than decreasing nocebo hyperalgesia, treatment choice may exacerbate pain outcomes when a painful procedure is repeatedly administered. As such, using choice as a strategy to mitigate nocebo outcomes should be treated with caution.

Choice over placebo administration enhances open-label placebo hypoalgesia.

ABSTRACT: Many studies indicate that deceptively administered placebos can improve pain outcomes. However, the deception involved presents an ethical barrier to translation because it violates informed consent and patient autonomy. Open-label placebos (OLPs), inert treatments that are openly administered as placebos, have been proposed as an ethically acceptable alternative. Early studies have suggested that OLP can improve pain outcomes, but important questions remain as to how to maximise OLP hypoalgesia to improve treatment outcomes in pain patients. This study investigated whether providing choice over when to administer an OLP treatment has the capacity to enhance OLP hypoalgesia using an electrocutaneous pain paradigm. One hundred thirty-two healthy volunteers were randomised to 3 types of treatment: OLP with choice, OLP without choice, and no treatment (natural history). The OLP groups were further randomised such that half were tested with a consistent pain intensity and the other half were tested with variable pain intensity to mimic day-to-day variability in pain intensity in health settings. The results indicated that treatment provided with choice exhibited greater OLP hypoalgesia than that provided without choice and that greater expectancy mediated this effect. Of interest, there was no evidence for OLP hypoalgesia without choice relative to natural history. Furthermore, variability in pain intensity did not affect OLP hypoalgesia. The current findings present novel evidence that choice over treatment administration may be a cheap and effective strategy for boosting the efficacy of OLPs in the clinical care of pain.

Choice Enhances Placebo Hypoalgesia More in Weaker Placebo Contexts: A Partial Reinforcement Study.

Providing individuals with choice over treatment has been found to enhance placebo hypoalgesia. However, this choice effect is not always present. The current study tested whether the strength of the placebo context influenced the effect of choice on placebo hypoalgesia. Using an established electrocutaneous pain paradigm, the choice effect was compared when placebo hypoalgesia was induced by Continuous Reinforcement (CRF) (strong placebo context) versus partial reinforcement (PRF) (weak placebo context). Healthy volunteers (N = 133) were randomized to receive either choice over treatment administration or no choice and then to placebo conditioning under either CRF (placebo always followed by surreptitious pain reduction during training) or PRF (placebo only followed by surreptitious pain reduction on half of the training trials). At the test, placebo hypoalgesia was greater and more resistant to extinction overall for those with choice. Importantly, however, the choice effect in enhancing the magnitude of placebo hypoalgesia was stronger after PRF than CRF. These results indicate that choice may have greater placebo-enhancing power in weaker placebo contexts. Therefore, choice may be a cheap and effective tool for improving clinical outcomes by facilitating placebo hypoalgesia when the existing treatment context is insufficient to produce placebo hypoalgesia itself. PERSPECTIVE: This study demonstrates that the enhancing effect of choice on placebo hypoalgesia is greater in a weaker placebo context. As such, offering choice could be an ethical way to effectively improve pain outcomes when placebo effects cannot be readily produced by the treatment context.

The nocebo effect across health outcomes: A systematic review and meta-analysis.

OBJECTIVE: The nocebo effect represents a growing concern in clinical settings. Nocebo effects occur when the treatment context generates negative expectancies that trigger the experience or worsening of negative symptoms beyond any effects attributable to the treatment itself. Despite being identified in a range of outcomes and conditions, from pain to Parkinson's disease, there has not been an attempt to systematically quantify the nocebo effects across health outcomes. The purpose of the present review was thus to systematically review and meta-analyze the nocebo literature to quantify the size of the nocebo effect across outcomes and examine which factors moderate the size of the nocebo effect, including process of induction, treatment type, or health outcome. METHOD: Systematic searches of PubMed, PychInfo, Medline, and Web of Science identified 130 (n = 8,219) independent eligible studies. To be included, studies had to include both a nocebo and control group/condition, which were compared to isolate the nocebo effect size. RESULTS: Overall, the magnitude of the nocebo effect was medium (g = 0.522) and highly heterogeneous. Two key moderators emerged: health outcome and process of induction. Here, the nocebo effect was medium for most somatic outcomes and affect, with no significant effect on worsening cognitive performance. Further, inducing nocebo effects through instruction in combination with conditioning produced larger nocebo effects. CONCLUSIONS: The present review suggests nocebo effects can be reliably induced across somatic health outcomes, and interventions that target the effect of instructions will be of critical importance to reducing the occurrence of nocebo effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Choice and the Placebo Effect: A Meta-analysis.

BACKGROUND: Choice has been proposed as a method of enhancing placebo effects. However, there have been no attempts to systematically evaluate the magnitude, reliability, and moderators of the influence of choice on the placebo effect. PURPOSE: To estimate the effect size of choice on the placebo effect and identify any moderators of this effect. METHODS: Web of Science, PsycINFO, EMBASE, and PubMed were systematically searched from inception to May 2021 for studies comparing placebo treatment with any form of choice over its administration (e.g., type, timing) to placebo treatment without choice, on any health-related outcome. Random-effects meta-analysis was then used to estimate the effect size associated with the influence of choice on the placebo effect. Meta-regression was subsequently employed to determine the moderating effect of factors such as type of choice, frequency of choice, and size of the placebo effect without choice. RESULTS: Fifteen independent studies (N = 1,506) assessing a range of conditions, including pain, discomfort, sleep difficulty, and anxiety, met inclusion criteria. Meta-analysis revealed that choice did significantly enhance the placebo effect (Hedges' g = 0.298). Size of the placebo effect without choice was the only reliable moderator of this effect, whereby a greater effect of choice was associated with smaller placebo effects without choice. CONCLUSIONS: Treatment choice can effectively facilitate the placebo effect, but this effect appears more pronounced in contexts where the placebo effect without choice is weaker. Because most evidence to date is experimental, translational studies are needed to test whether providing choice in clinical scenarios where placebo effects are weaker may help boost the placebo effect and thereby improve patient outcomes.

Instrumental Control Enhances Placebo Analgesia.

Placebo analgesia is a robust phenomenon readily observed in both experimental and clinical settings. While researchers have begun to unpack its psychobiological mechanisms, important questions remain regarding how we can capitalize on the placebo effect to improve clinical pain outcomes. The current study tested whether providing individuals with instrumental control-that is, control over if and when they administer a treatment-is capable of enhancing placebo analgesia. Using an established electrocutaneous pain design, 87 healthy volunteers either received placebo conditioning with instrumental control over treatment administration, standard passive placebo conditioning without any control over treatment administration, or were allocated to natural history control group with no conditioning and were later tested at equivalent shock intensity with and without placebo applied. Both placebo groups demonstrated initial placebo analgesia. Importantly, however, those provided with instrumental control demonstrated significantly larger and longer lasting placebo analgesia as well as reduced anticipatory autonomic arousal than those receiving standard passive placebo conditioning. This suggests that providing instrumental control over treatment administration can facilitate placebo analgesia by enhancing its magnitude and durability. As such, providing instrumental control over treatment administration may be a cheap and ethical method of using the placebo effect to improve clinical pain outcomes. PERSPECTIVE: Placebo research typically involves passive designs where individuals have no control over treatment administration. We present novel data demonstrating that providing control over treatment administration substantially enhances both the magnitude and duration of placebo analgesia. As such, where possible, providing control may improve clinical pain outcomes via the placebo effect.