Placebo Outperforms Drug in Oxford StudyPositive expectations of a treatment may be more powerful than the drug itself when it comes to getting well.  According to a brain imaging study at Oxford University, volunteers who believed their medication would help actually doubled the natural physiological or biochemical effects of an opioid drug.

On the other hand, it was found that negative expectations could actually override the effects of the powerful pain-relieving drug.

Prior placebo effect studies have shown that the body can truly react in response to sugar pills or saline injections. Patients get better after unknowingly taking a dummy pill, simply because they believe it would help.

This “mind game,” however, is a very real physiological effect.  Its opposite is called the “nocebo” effect, when patients have worse outcomes as a result of their doubts concerning a medical treatment.

In the new study, researchers sought to take these ideas further by observing what would happen if a participant’s expectations were manipulated and how this might influence his or her response to an active drug.

The Oxford team, along with colleagues from the University Medical Center Hamburg-Eppendorf in Germany, Cambridge University, and the Technische Universität München, investigated these effects by giving 22 healthy adult volunteers an opioid drug and manipulating their expectations of how much pain relief they would feel at different stages during the treatment.

“Doctors shouldn’t underestimate the significant influence that patients’ negative expectations can have on outcome,” said lead author Irene Tracey, Ph.D., of the Centre for Functional Magnetic Resonance Imaging of the Brain at Oxford University.

“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.”

During the Oxford study, participants were placed in an MRI scanner; heat was applied to the leg at a level where they began to feel pain, a point at which each volunteer had rated the pain as a 70 on a scale of 1 to 100.  A strong opioid drug for relief was set up on an intravenous line.

An initial control run was carried out; then, unknown to the participants, the researchers began releasing the drug to determine the effects on participants when they had no knowledge or expectation of treatment. The average initial pain rating of 66 went down to 55.

Then, participants were informed that they would be given a pain-relief drug; however, they simply continued to receive the opioid at the same dose as before. The average pain ratings dropped even more to 39.

Finally, researchers told the volunteers that the drug had been stopped and warned that the pain levels would go up. Once more, the opioid drug was still being administered in the same exact way. However, their pain intensity increased to a rating of 64. The pain was just as intense as it had been at the beginning of the study, when they received no pain relieving drug.

Brain imaging was used to confirm the participants’ reports of pain relief. MRI scans revealed that the brain’s pain networks responded according to the volunteers’ expectations at each stage, and these matched their reports of pain.

These results reveal that the volunteers’ pain experiences fluctuated with their expectations, even when the administration of pain relief remained the same.

Tracey noted that this study was administered to a small, healthy group of volunteers, and that these manipulations of the participants’ treatment beliefs were short-term, and not sustained.  However, she said it’s important not to underestimate the power of these expectations during any treatment, and that physicians need to know how to manage that.

Tracey believes this knowledge would also be beneficial for the design of clinical trials, which are often set up to compare a candidate drug against a dummy pill to determine the drug’s effect 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 minimize any negative expectations to make sure we’re not masking true efficacy in a trial drug,” she said.

The study is published in Science Translational Medicine and was funded by the Medical Research Council and German research funders.

Source:  University of Oxford