HOW TO PREVENT CANCERS

by Bianca Nogrady

Technically a placebo isn't supposed to have any effect, but a growing body of evidence suggests harnessing the power of placebos could boost the effectiveness of a range of medical treatments.

Over the years, the placebo has earned an unfair reputation as an instrument of medical fakery; a white lie to convince unsuspecting patients they are being treated when in fact their treatment is nothing more than a sugar pill or surgical sleight of hand.

However growing evidence suggests the placebo and its effects are far more significant in modern medical practice than many of us realised. Some are arguing that instead of viewing it with disdain, we should instead be embracing it.

The word 'placebo' has its origins in the Latin for 'to please'. While its meaning has varied over the centuries, it has come to be used as the name for an inert or simulated medical therapy, such as a sugar pill, saline injection or sham procedure, that is used precisely because it is assumed not to do anything.

So if the placebo substance or procedure is truly, medically inert, how can it have an effect? Dr Damian Finniss says it's because we expect it to.

"What we're really doing when we give a placebo is we're simulating normal treatment without actually delivering a particular treatment itself," says Finniss, a clinician and researcher at the Pain Management Research Institute, Sydney Medical School.

What therefore happens is that your brain effectively fills in the gap created by the absent medication or treatment, and does so with remarkable physiological precision.

"In the case of pain, where we've done a lot of research, if you give someone a morphine-like drug repeatedly, and then you switch it over to a placebo, that placebo effect that we see is mediated by morphine-like chemicals in the brain," Finniss says.

"If you do the same thing with a non-steroidal anti-inflammatory and you give the real drug for several days and switch to a sugar tablet, that mechanism is completely different – in fact that's mediated by our endogenous cannabinoids – even when the patient doesn't know."

Research also shows that, depending on what effect a placebo is expected to have, it influences different parts of the brain. If you are given a sugar tablet and told it will relieve pain, then a certain network in your brain is activated; however, if you are given a sugar tablet and told it will improve the symptoms of a movement disorder then a different network will be activated.

"So what was deemed to be very simple – that some people got better to a sugar tablet – in fact we realise there's a highly selective series of mechanisms that are activated depending on the therapeutic context in which we receive treatment," Finniss says.

This is not to say that a placebo can cure cancer or an infection. Placebos appear to be most effective at relieving the symptoms of disease, such as pain, but not the disease itself.

So while a placebo inhaler won't necessarily change the way the lung works during an asthma attack, it could change the person's perception of breathlessness so that it doesn't affect them as much.

"You're not necessarily targeting disease processing but you're targeting symptoms of disease because that's a much higher level function in the brain," Finniss explains.

This is what makes placebos so valuable in medical research, because they allow researchers to separate out the true biological effect of a drug or intervention from its placebo component. In the case of some drugs, such as anti-depressants, there is a particularly large placebo effect – so much so that when data from a number of placebo-controlled antidepressant trials was analysed it showed the actual clinical benefit from the antidepressant falls below the line of clinical significance.

Similarly, a review of acupuncture studies found only a small to medium difference between acupuncture and 'sham' acupuncture in the treatment of some conditions.

But the placebo effect extends even further. There is growing evidence that the result of just about any medical treatment is partly due to the placebo effect, even if a placebo isn't given, because the ritual and interaction of a medical consultation induces a placebo effect all of its own.

For example, a study was done with patients receiving intravenous morphine. One group of patients were administered the morphine by a doctor, while the other group of patients were hooked up to an intravenous line through which morphine was delivered, by computer, at an unspecified time, without the doctor being present.

Both patients were receiving the same dose of morphine yet it was around half as effective at relieving pain in the patients who weren't given it by a doctor and didn't know when they were receiving it.

The discovery has profound implications for medical practice.

"Modern medicine needs to be aware of this idea that there is biological validity to the therapist-doctor interaction and the ritual of medicine and surgery," Finniss says.

"The outcome is not solely due to the particular therapy itself, but it's due to that therapy plus these other contextual mechanisms which we call placebo because the only way to see them by themselves is to run a placebo simulation, give a sugar tablet or a sham surgery."

It places a therapeutic value on good old-fashioned bedside manner – something Finniss argues should be incorporated into medical training.

"We need to realise that there are very specific biological pathways that are activated in the therapeutic encounter and ritual, and therefore once we start to learn more about them, I think the onus is going to be on clinicians or certainly the next generation of clinicians, to think about the way in which they deliver the treatments they deliver and perhaps not just focus on the technical aspects of the treatment alone."

Placebo-controlled trials are a mainstay of modern medical research, but what if the use of placebo in a trial actually meant the active treatment would have less of an effect?

Researchers recently looked at clinical trials of a type of drug called a dopamine agonist, used to treat Parkinson's disease. They compared the results of trials where patients were randomised to either the active drug or placebo group, and trials where patients received either the active drug or another treatment (called a head-to-head trial).

Patients were blinded to their treatment, meaning they did not know whether they were receiving placebo, active drug or comparison drug. Despite this, researchers found that patients in placebo-controlled trials had less of a response to the dopamine agonist, compared to the patients in the head-to-head trial, even though in both trials, patients were receiving the same dose of the drug.

The explanation? The researchers suggested that patients going into placebo-controlled trials know there's a chance they will get an inactive substance, so that actually reduces their expectation of benefit, whereas patients in the head-to-head trial know they are going to get one of two active drugs. The researchers coined the term 'Lessebo effect' to describe the phenomenon, and suggested it might be a game-changer for the design of clinical trials.

Published 11/11/2013