Study finds knowingly taking placebo pills eases pain

Conventional medical wisdom has long held that placebo effects depend on patients' belief they are getting pharmacologically active medication. A paper published today in the journal Pain is the first to demonstrate that patients who knowingly took a placebo in conjunction with traditional treatment for lower back pain saw more improvement than those given traditional treatment alone.

15 oct 2016--"These findings turn our understanding of the placebo effect on its head," said joint senior author Ted Kaptchuk, director of the Program for Placebo Studies and the Therapeutic Encounter at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School. "This new research demonstrates that the placebo effect is not necessarily elicited by patients' conscious expectation that they are getting an active medicine, as long thought. Taking a pill in the context of a patient-clinician relationship - even if you know it's a placebo - is a ritual that changes symptoms and probably activates regions of the brain that modulate symptoms."
Kaptchuk, with colleagues at Instituto Superior de Psicologia Aplicada (ISPA) in Lisbon, Portugal, studied 97 patients with chronic lower back pain (cLBP), which causes more disability than any other medical condition worldwide. After all participants were screened and examined by a registered nurse practitioner and board certified pain specialist, the researchers gave all patients a 15-minute explanation of the placebo effect. Only then was the group randomized into one of two groups; the treatment-as-usual (TAU) group or the open-label placebo (OLP) group.
The vast majority of participants in both groups (between 85 and 88 percent) were already taking medications - mostly non-steroidal anti-inflammatories (NSAIDS) - for their pain. (Patients taking opioid medications were excluded from the trial.) Participants in both the TAU and OLP groups were allowed to continue taking these drugs, but were required not to change dosages or make any other major lifestyle changes, such as starting an exercise plan or new medication, which could impact their pain.
In addition, patients in the OLP group were given a medicine bottle labeled "placebo pills" with directions to take two capsules containing only microcrystalline cellulose and no active medication twice daily.
At the end of their three-week course of pills, the OLP group overall reported 30 percent reductions in both usual pain and maximum pain, compared to 9 percent and 16 percent reductions, respectively, for the TAU group. The group taking placebo pills also saw a 29 percent drop in pain-related disability. Those receiving treatment as usual saw almost no improvement by that measure.
"It's the benefit of being immersed in treatment: interacting with a physician or nurse, taking pills, all the rituals and symbols of our healthcare system," Kaptchuk said. "The body responds to that."
"Our findings demonstrate the placebo effect can be elicited without deception," said lead author, Claudia Carvalho, PhD, of ISPA. "Patients were interested in what would happen and enjoyed this novel approach to their pain. They felt empowered."
Kaptchuk speculates that other conditions with symptoms and complaints that are based on self-observation (like other kinds of pain, fatigue, depression, common digestive or urinary symptoms) may also be modulated by open-label treatment.
"You're never going to shrink a tumor or unclog an artery with placebo intervention," he said. "It's not a cure-all, but it makes people feel better, for sure. Our lab is saying you can't throw the placebo into the trash can. It has clinical meaning, it's statically significant, and it relieves patients. It's essential to what medicine means."
"Taking placebo pills to relieve symptoms without a warm and empathic relationship with a health-care provider relationship probably would not work," noted Carvalho.


Provided by Beth Israel Deaconess Medical Center

Clinicians can unintentionally prompt nocebo effect

The nocebo effect, or induction of a symptom perceived as negative by sham treatment and/or the suggestion of negative expectation, may arise from suggestions by doctors and nurses, according to a study published in Deutsches Ärzteblatt International.

05 aug 2012-- The nocebo effect, or induction of a symptom perceived as negative by sham treatment and/or the suggestion of negative expectation, may arise from suggestions by doctors and nurses, according to a study published in Deutsches Ärzteblatt International.

Winfried Häuser, M.D., from Technische Universität München, and colleagues conducted a literature review to investigate nocebo phenomena in clinical practice.

The researchers found that the underlying mechanisms behind nocebo responses included learning by Pavlovian conditioning and reaction to expectations induced by verbal information or suggestion. Unintentional negative suggestion on the part of physicians and nurses was found to trigger nocebo responses. The patients' negative expectations, along with being given information about possible complications, increased the likelihood of adverse effects. A nocebo effect was found to cause adverse events under treatment with medications.

"Physicians face an ethical dilemma, as they are required not just to inform patients of the potential complications of treatment, but also to minimize the likelihood of these complications, i.e., to avoid inducing them through the potential nocebo effect of thorough patient information," the authors write. "Possible ways out of the dilemma include emphasizing the fact that the proposed treatment is usually well tolerated, or else getting the patient's permission to inform less than fully about its possible side effects."

Two authors disclosed financial ties to the pharmaceutical industry.

More information: Full Text

Expecting the best, fearing the worst with placebo effect

(20 feb 2011) -- Poor expectations of treatment can override all the effect of a potent pain-relieving drug, a brain imaging study at Oxford University has shown.

In contrast, positive expectations of treatment doubled the natural physiological or biochemical effect of the opioid drug among the healthy volunteers in the study.

The study of the placebo effect – and its opposite the nocebo effect – is published in Science Translational Medicine. The findings suggest that doctors may need to consider dealing with patients’ beliefs about the effectiveness of any treatment, as well as determining which drug might be the best for that patient.

"Doctors shouldn’t underestimate the significant influence that patients' negative expectations can have on outcome," says Professor Irene Tracey of the Center for Functional Magnetic Resonance Imaging of the Brain at Oxford University, who led the research.

"For example, people with chronic pain will often have seen many doctors and tried many drugs that haven’t worked for them. They come to see the clinician with all this negative experience, not expecting to receive anything that will work for them. Doctors have almost got to work on that first before any drug will have an effect on their pain."

The placebo effect describes the improvements seen when patients – unknowingly – are given dummy pills or sham treatments but believe it will do them good. This is a very real physiological effect; it is not just about patients ‘feeling’ better. The nocebo effect is the opposite: patients see poorer outcomes as the result of doubts about a medical treatment.

Previous studies have investigated the basis of the placebo effect, when using sugar pills or saline injections for example, and confirmed it can elicit a real response.

This new research, funded by the Medical Research Council and German research funders, goes a step further by examining how manipulating participants’ expectations can influence their response to an active drug.

The Oxford University team, along with colleagues from the University Medical Center Hamburg-Eppendorf in Germany, Cambridge University, and the Technische Universität München, set out to investigate these effects among 22 healthy adult volunteers by giving them an opioid drug and manipulating their expectations of the pain relief they might receive at different points.

The volunteers were placed in an MRI scanner and heat applied to the leg at a level where it begins to hurt – set so that each individual rated the pain at 70 on a scale of 1 to 100. An intravenous line for administration of a potent opioid drug for pain relief was also introduced.

After an initial control run, unknown to the participants, the team started giving the drug to see what effects there would be in the absence of any knowledge or expectation of treatment. The average initial pain rating of 66 went down to 55.

The volunteers were then told that the drug would start being administered, although no change was actually made and they continued receiving the opioid at the same dose. The average pain ratings dropped further to 39.

Finally, the volunteers were led to believe the drug had been stopped and cautioned that there may be a possible increase in pain. Again, the drug was still being administered in the same way with no change. Their pain intensity increased to 64. That is, the pain was as great as in the absence of any pain relief at the beginning of the experiment.

The researchers used brain imaging to confirm the participants’ reports of pain relief. MRI scans showed that the brain’s pain networks responded to different extents according to the volunteers’ expectations at each stage, and matching their reports of pain.

This showed the volunteers really did experience different levels of pain when their expectations were changed, although the administration of pain relief remained constant.

Professor Tracey notes that these results have been seen in a small, healthy group of volunteers, and that these are short-term, not sustained, manipulations of the participants’ beliefs about the treatment.

But she says it’s important not to underestimate the strength of the effect of such expectations on any treatment, and that clinicians need to know how to manage that.

Professor Tracey says there may also be lessons for the design of clinical trials. These are often carried out comparing a candidate drug against a dummy pill to see if there is any effect of a drug above and beyond that of the placebo.

"We should control for the effect of people’s expectations on the results of any clinical trial. At the very least we should make sure we minimise any negative expectations to make sure we’re not masking true efficacy in a trial drug."

More information: http://stm.science … a14.abstract

Provided by Oxford University