Harmful placebos

Harmful placebos. Credit: Shutterstock

How could a sugar pill placebo cause harm? A new review of data from 250,726 trial participants has found that 1 in 20 people who took placebos in trials dropped out because of serious adverse events (side effects). Almost half of the participants reported less serious adverse events. The adverse events ranged from abdominal pain and anorexia to burning, chest pain, fatigue, and even death. The study found that the apparently strange phenomena of sugar pills producing harm can be explained by misattribution and negative expectations.

Misattribution

17 dec 2018--Someone in a trial might have a symptom like a stomach ache for any number of reasons that are not related to the trial. Because they are in a trial, they think the trial intervention caused the ache. This gets reported as an adverse event when it would have happened anyway.

Negative expectations

The way patients are warned about adverse events can sometimes cause an adverse event. Effects of negative expectations are called 'nocebo' ('negative placebo') effects. "Our study provided preliminary data indicating that some trial participants experience nocebo effects," reports lead author Jeremy Howick. Other studies provide more definitive evidence that the way patients are warned about adverse events can affect whether they report them. For example, a study found that patients in a randomised trial of aspirin or sulfinpyrazone for treating unstable angina who were warned about gastrointestinal adverse events were six times more likely to withdraw from the study due to reported gastrointestinal adverse events. A more recent study published last year in The Lancet found that patients were more likely to report adverse events when they knew they were taking statins, compared to when they didn't. This is probably because the belief that statins cause adverse events like muscle pain can actually produce the muscle pain.
Finding ways to reduce adverse events among patients in placebo groups is important for improving trial quality (since fewer participants will drop out), and improving trial ethics (by avoiding harm). The question is: how?
"Misattribution can be hard to avoid," says Jeremy Howick, 'because it's hard for someone to know whether a symptom like a stomachache would have occurred anyways or whether it was because of the trial. However, I believe we can reduce the harm caused by negative expectations."
For example, telling patients that a new treatment is safe for 90% of patients contains the same information as saying it causes adverse events like headaches in 10% of patients. But the second way may be more likely to actually cause the adverse events than the first.
Unfortunately, guidance for informing trial participants about trial intervention harms, in a way that is ethical, understandable, and does not produce nocebo effects, is currently under-researched. A recent study suggested that information provided to trial participants often fails to tell them what they wish to know, and that it is presented in a way that is difficult to understand. Ongoing research at the Universities of Oxford and Cardiff is looking at ways to inform patients in trials about the best way to provide balanced information about the benefits and harms of participating in trials. Their preliminary research suggests that patients are provided more information about trial harms than trial benefits.
Says co-author Professor Kerry Hood (Director of Cardiff Centre for Trials Research): "We believe it is possible to balance the information about trial benefits and harms in a way that is fact-based and that does not cause unnecessary harm. This can be achieved by ensuring that the benefits, as well as the harms, are explained in a way patients understand."
The full paper, "Rapid Overview of Systematic Reviews of Nocebo Effects Reported by Patients Taking Placebos in Clinical Trials," is published in Trials.

More information: Jeremy Howick et al. Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials, Trials (2018). DOI: 10.1186/s13063-018-3042-4


Provided by University of Oxford

The nocebo effect: Media reports may trigger symptoms of a disease

Media reports about substances that are supposedly hazardous to health may cause suggestible people to develop symptoms of a disease even though there is no objective reason for doing so. This is the conclusion of a study of the phenomenon known as electromagnetic hypersensitivity. Those affected report experiencing certain symptoms on exposure to electromagnetic waves, such as those emitted by cell phones, and these take the form of physical reactions. With the help of magnetic resonance imaging, it has been demonstrated that the regions of the brain responsible for pain processing are active in such cases. "Despite this, there is a considerable body of evidence that electromagnetic hypersensitivity might actually be the result of a so-called nocebo effect," explained Dr. Michael Witthöft of Johannes Gutenberg University Mainz (JGU). "The mere anticipation of possible injury may actually trigger pain or disorders. This is the opposite of the analgesic effects we know can be associated with exposure to placebos." The new study illustrates how media reports about health risks may trigger or amplify nocebo effects in some people.

08 may 2013--Frequently, the media reports on the potential health risks associated with the electromagnetic fields (EMFs) produced by cell phones, cell phone masts, high-voltage lines, and Wi-Fi devices. People who are sensitive to electromagnetic fields report symptoms such as headaches, dizziness, burning or tingling sensations on their skin, and they attribute these effects to this radiation. Some people actually skip work or withdraw from their social environment because of their electromagnetic hypersensitivity and in extreme cases they may even move to remote regions to get away from electrical equipment altogether. "However, tests have shown that the people affected are unable to tell if they have really been exposed to an electromagnetic field. In fact, their symptoms are triggered in exactly the same way if they are exposed to genuine and sham fields," added Witthöft. The so-called nocebo effect was initially identified during pharmaceutical trials. Subjects were observed to exhibit undesirable side effects even though they were not receiving the medication but merely a placebo.

Witthöft undertook the current study in collaboration with G. James Rubin during a research stay at King's College in London. The 147 test subjects were first shown a television report. One group of participants watched a BBC One documentary, which dealt in no uncertain terms with the potential health hazards supposedly associated with cell phone and WiFi signals. The other group watched a report on the security of Internet and cell phone data. Then all the subjects in both groups were exposed to fake WiFi signals that they were told were real. Even though they were not exposed to any radiation, some of the subjects developed characteristic symptoms: 54 percent of the subjects reported experiencing agitation and anxiety, loss of concentration or tingling in their fingers, arms, legs, and feet. Two participants left the study prematurely because their symptoms were so severe that they no longer wanted to be exposed to the assumed radiation. It became apparent that the symptoms were most severe among the subjects who had high pre-existing anxiety as a result of viewing the documentary about the possible hazards of electromagnetic radiation.

The study thus demonstrates that sensationalized media reports on potential risks, which often lack scientific evidence, can have a significant effect on the health of large sections of the population. Such speculation on health hazards most likely has more than just a short-term impact like that of a self-fulfilling prophesy; it is likely that over the long term some people begin to believe that they are sensitive and develop symptoms in certain situations when exposed to electrosmog. "Science and the media need to work together more closely and make sure that reports of possible health hazards from new technologies are as accurate as possible and are presented to the public using the best available scientific data," said Witthöft, drawing consequences from the study findings.

More information: Michael Witthöft, G. James Rubin (2013), Are media warnings about the adverse health effects of modern life self-fulfilling? An experimental study on idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF), Journal of Psychosomatic Research, DOI:10.1016/j.jpsychores.2012.12.002

Provided by Universitaet Mainz