The belief that a drug will not work can be potent enough to actually override its efficacy, a brain imaging study with patients at Oxford University has shown.

The research demonstrated that altering patients' expectations of treatment could either enhance or diminish the efficacy of strong painkillers, a finding which could have far reaching consequences both in the clinic and drug development settings.

While plenty of evidence exists to support the existence of the placebo effect, this new research, which received cash backing from the Medical Research Council and German research funders, goes further by examining how the manipulation of expectations can influence a response to an active drug.

The team, which included researchers from Oxford University, the University Medical Center Hamburg-Eppendorf in Germany, Cambridge University, and the Technische Universität München, placed 22 healthy adult volunteers in an MRI scanner, hooked them up to an intravenous line for administration of a powerful opioid based painkiller, and applied heat to the leg at a level where it begins to hurt.

An initial control pain rating of 66 (out of 100) dropped to 55 when the painkiller was secretly given, but dropped further to 39 after the patients were actually told that treatment was being administered, even though it was given at the same dose.  

Volunteers were then led to believe the drug had been stopped and warned of a potential increase in pain. Despite the fact that the drug was in reality still being administered, pain intensity increased to 64 - a similar magnitude to that reported in the true absence of any pain relief at all. 

Expectations and experience

Moreover, brain scans actually showed that the study participants really did experience different levels of pain when their expectations changed, even though the painkiller dose remained constant. 

The findings, published in the journal Science Translational Medicine, suggest that doctors should consider dealing with patient expectations on drug effectiveness before the start of any treatment, the researchers said.

"Doctors shouldn’t underestimate the significant influence that patients’ negative expectations can have on outcome," stressed study lead Professor Irene Tracey of the Centre for Functional Magnetic Resonance Imaging of the Brain at Oxford University.

And aside from the potential implications for clinical practice, Tracey points out that the findings are also particularly relevant to drug research. "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," she notes.