The American Journal of Bioethics, Volume 12, Issue 3, Page 35-36, March 2012.

The principle of informed consent obligates physicians to explain possible side effects when prescribing medications. This disclosure may itself induce adverse effects through expectancy mechanisms known as nocebo effects, contradicting the principle of nonmaleficence. Rigorous research suggests that providing patients with a detailed enumeration of every possible adverse event—especially subjective self-appraised symptoms—can actually increase side effects. Describing one version of what might happen (clinical “facts”) may actually create outcomes that are different from what would have happened without this information (another (...) version of “facts”). This essay argues that the perceived tension between balancing informed consent with nonmaleficence might be resolved by recognizing that adverse effects have no clear black or white “truth.” This essay suggests a pragmatic approach for providers to minimize nocebo responses while still maintaining patient autonomy through “contextualized informed consent,” which takes into account possible side effects, the patient being treated, and the particular diagnosis involved. (shrink)

The material presented at this conference pointed to a new dimension in the prosecution of activities that seek to relieve people of disease. While the simple instrument of the placebo may show those interested in the efficacy of physiologically active chemicals the extent to which the chemical of interest is actually active, the surprising outcome of such studies is that the placebo per se is worthy of more general study. This, when taken further, points to the ways in which mind (...) can influence the matter of the body. Of course, mind itself is an activity of matter, so we may retain the experimental approach that has told us about the world outside ourselves to examine the world that is inside our brains. New techniques and approaches to these once intractable problems are now in train. Where they will lead us we cannot predict, but as with the emergence of all new tools, we have to adopt those ethics that will carry us forward with the expectation that we will maximise benefits and minimise harms. (shrink)

Psychosis is associated with distorted perceptions and deficient bottom-up learning such as classical fear conditioning. This has been interpreted as reflecting imprecise priors in low-level predictive coding systems. Paradoxically, overly strong beliefs, such as overvalued beliefs and delusions, are also present in psychosis-associated states. In line with this, research has suggested that patients with psychosis and associated phenotypes rely more on high-order priors to interpret perceptual input. In this behavioural and fMRI study we studied two types of fear learning, i.e., (...) instructed fear learning mediated by verbal suggestions about fear contingencies and classical fear conditioning mediated by low level associative learning, in delusion proneness—a trait in healthy individuals linked to psychotic disorders. Subjects were shown four faces out of which two were coupled with an aversive stimulation while two were not in a fear conditioning procedure. Before the conditioning, subjects were informed about the contingencies for two of the faces of each type, while no information was given for the two other faces. We could thereby study the effect of both classical fear conditioning and instructed fear learning. Our main outcome variable was evaluative rating of the faces. Simultaneously, fMRI-measurements were performed to study underlying mechanisms. We postulated that instructed fear learning, measured with evaluative ratings, is stronger in psychosis-related phenotypes, in contrast to classical fear conditioning that has repeatedly been shown to be weaker in these groups. In line with our hypothesis, we observed significantly larger instructed fear learning on a behavioural level in delusion-prone individuals compared to non-delusion-prone subjects. Instructed fear learning was associated with a bilateral activation of lateral orbitofrontal cortex that did not differ significantly between groups. However, delusion-prone subjects showed a stronger functional connectivity between right lateral orbitofrontal cortex and regions processing fear and pain. Our results suggest that psychosis-related states are associated with a strong instructed fear learning in addition to previously reported weak classical fear conditioning. Given the similarity between nocebo paradigms and instructed fear learning, our results also have an impact on understanding why nocebo effects differ between individuals. (shrink)

Drug recalls and lawsuits against pharmaceutical manufacturers are accompanied by announcements emphasizing harmful drug side-effects. Those with elevated health anxiety may be more reactive to such announcements. We evaluated whether health anxiety and financial incentives affect subjective symptom endorsement, and objective outcomes of cognitive and physiological functioning during a mock drug recall. Hundred and sixty-one participants reported use of over-the-counter pain medications and presented with a fictitious medication recall via a mock Food and Drug Administration website. The opportunity to join (...) a class-action lawsuit was manipulated. We assessed health anxiety, recalled drug usage, blood pressure, heart rate, and performance on a computerized Trail Making Test. Symptom endorsement was strongly predicted by health anxiety. When combined, three health anxiety measures explained 28.5% variance. These effects remain strong after controlling for depression and anxiety. Litigation condition did not predict symptom endorsement. Blood pressure and heart rate were modestly predicted by health anxiety, but not by litigation condition. TMT performance was consistently predicted by health anxiety, with higher scores associated with poorer performance. Although there were no main effects for litigation, interactions consistently emerged for the TMT, with generally poorer performance for those with higher health anxiety in the non-litigation condition; whereas health anxiety was unrelated to performance for the litigation condition. All but one participant joined the litigation when given the opportunity, despite a healthy sample and minimal use of pain medication. Subsequent data from 67 individuals with no mention of the FDA scenario or litigation showed that health anxiety still significantly predicts symptom endorsement, but the explained variance is less than half that obtained in the FDA scenario. The findings suggest that health anxiety plays a significant role in adverse symptom reporting, beyond anxiety or depression, and this effect is independent of the presence of the FDA recall. The lack of differences for health anxiety and symptom endorsement between litigation and non-litigation conditions rules out malingering. Although it is general practice in drug recalls to list potential adverse side effects caused by medications, this may elicit unintended symptom experiences and health anxious individuals may be more susceptible. (shrink)

Background Thorough information of the patient is an integral part of the process of shared decision making. We aimed to investigate if detailed information about medication may induce nocebo effects. Methods We conducted a randomized, single-blind, pilot-study including n = 51 psychiatric in-patients aged between 18 and 80 years with a depressive disorder and accompanying sleeping disorders. In the intervention group we provided thorough information about adverse effects, while the control group received only a simple consent procedure. In both groups, (...) patients received an open-label placebo pill instead of their sleeping medication. Results No statistically significant differences between the intervention group and the control group were found regarding the main outcome parameter. Conclusion In this study, we were not able detect an effect of informed consent vs. simple consent on the emergence of placebo or nocebo effects. This finding is contrary to most assumptions and publications about this topic. Trial registration Trial registration number: DRKS00017653, registered August 30th 2018. Retrosprectively registered. (shrink)

Nocebo effects occur when an adverse effect on the patient arises from the patient's own negative expectations. In accordance with informed consent, providers often disclose information that results in unintended adverse outcomes for the patient. While this may adhere to the principle of autonomy, it violates the doctrine of “primum non nocere,” given that side-effect disclosure may cause those side effects. In this article we build off previous work, particularly by Wells and Kaptchuk and by Cohen :3–11.[Taylor & Francis Online], (...) [Web of Science ®] [Google Scholar]), to suggest ethical guidelines that permit nondisclosure in the case when a nocebo effect is likely to occur on of the basis of nonmaleficence. We accept that that autonomy vis-à-vis informed consent must be forestalled, but salvage much of its role by elaborating a practical clinical approach to postencounter follow-up. In doing so, we reconcile a clinically practicable process of determining conditions of disclosure with long-standing ethical commitments to patients. (shrink)