‘Mind-body’ Healing: Success of Placebo Trials Challenges Medical Thinking

Damien Finniss was working as a physiotherapist when, on a still winter’s afternoon in 2001, he set up his treatment table in a shed at the perimeter of a Sydney footy ground.

As players came off with sundry aches – a pulled hammy here, a calf strain there – Finniss ministered to them with therapeutic ultrasound, a device that applies sound waves to the injured area with a handheld probe.

“I treated in excess of five or six athletes during the training session. I’d treat them for five or 10 minutes and they’d say ‘I feel much better’ and run back on to the training field,” recalls Finniss, now a medical doctor and Associate Professor at the University of Sydney’s Pain Management and Research Institute.

“But, at the end of the session, I realised that I’d, basically, had the machine turned off.”

Forgetting to switch his device on at the wall, to no apparent detriment, was a light bulb moment that led Finniss to become a leading researcher on the placebo effect – the power of treatments with no active ingredients to heal the sick, sometimes dramatically.

“I’ve seen people who have had terrible arthritic pain for five or 10 years, receive a placebo injection, stand up, and walk straight out,” says Finniss, referring to patients in a clinical trial he ran.

Indeed, sham treatments in the form of sugar pills, fake creams and saline injections have delivered relief to people with depression, psoriasis and Parkinson’s disease, to name a few.

But the placebo has an image problem which has made it something of a dirty little secret in the medical profession.

It was widely thought that, for a placebo to work, doctors had to deceive patients that they were getting the real deal, and that’s problematic for a profession keen to promote informed consent.

But a new study casts doubt on whether deceit is necessary at all and, along with a swag of research showing some remarkable placebo effects, raises big questions about whether placebos should now enter the mainstream as a legitimate item for doctors to prescribe.

Led by Oxford University’s Jeremy Howick, the study examined five trials of so-called “open label” placebos, in which participants are told they are getting a dummy pill, sometimes with the advice that it has been shown to work through a “mind-body” healing mechanism.

And for conditions that included lower back pain, irritable bowel syndrome, hay fever, depression and ADHD, giving a placebo honestly, the researchers concluded, worked.

“If there’s evidence it’s effective, I don’t see huge harm with a health professional openly administering a placebo which the patient is fully aware of,” says Ben Colagiuri, a psychology researcher at the University of Sydney.

In April, Colagiuri published a meta-analysis of 13 studies that concluded placebo sleeping pills, whose real counterparts notched up nearly 3 million prescriptions in Australia in 2013-2014, significantly improved sleep quality.

The possibilities would seem almost limitless.

Adding a fake pill to the doctor’s bag could reduce medical costs and undercut the burden of disease – adverse reactions to prescription drugs are, on one estimate, the fourth leading cause of death in the United States.

But both Finniss and Colagiuri point out that leveraging the placebo effect isn’t just about giving fake pills. The key is to raise patients’ expectations of a positive result, something that also kicks in when real drugs are prescribed.

For Finniss, a striking example of placebo power is the so-called “open-hidden” effect.

A pain killer, such as morphine, can be twice as effective if the patient is told they are getting it (open) compared to receiving it unknowingly via an infusion (hidden).

“For every medical treatment, part of what we do is a receptor – or an anatomical-based treatment – and part of it is a treatment of a patient’s brain, through ritual,” says Finniss.

For the pain management doctor, that means the theatre of medicine is key, from the austerity of the consulting room, to taking the time to explain a treatment’s likely effects, even their decision to dress more formally.

But behind the performance of healing is some strong science.

Simply believing an analgesic will work releases the body’s endogenous pain killers and activates the same brain regions as the bona fide drug.

“Part of the outcome of what I do on any given day is the way I interact with the patients and not necessarily the technology, or the tablets, or the anaesthetic,” says Finniss.

That interaction is also the focus of Colagiuri’s research.

He’s looking at the placebo’s evil twin, the so-called “nocebo” effect, which happens when a patient’s pessimism about treatment becomes self-fulfilling, and they get bad results.

“We’ve shown that if you give a placebo treatment for sleep difficulty, and you warn half of the people about side effects but don’t warn the other half, the people you warn report more side effects,” says Colagiuri.

He’s aiming to reverse that by exploiting a psychological quirk familiar to anyone who’s made more than a cursory survey of supermarket shelves.

Those bright food packets are labelled “98 per cent fat-free” not “2 per cent fat” because, although they’re statistically identical, positive reference to the F-word could send the weight-conscious scurrying.

Colagiuri is deploying similar tactics to reduce drug side effects.

An antidepressant with, for example, a 30 per cent chance of causing sexual dysfunction, can be reframed as having a 70 per cent chance of not causing the problem.

“You’re giving exactly the same information so, therefore, maintaining full informed consent, but framing it in such a way to try to minimise negative expectancies,” says Colagiuri.

There is, however, an important caveat over the entire placebo project.

In 2011 a study published in the New England Journal of Medicine found that asthmatics treated with a placebo inhaler felt nearly as good as those who got the real treatment.

And while that might sound positive, the problem was their lung function barely improved, which prompted criticism that placebos could make sick people merely feel better, and cause them to delay potentially life-saving treatment.

That concern is real, but there is also a growing tranche of research showing placebos can produce a genuine biological response that could affect the disease process itself.

And it traces back to a gold-plated study from the archive.

In the 1970s the late psychologist Robert Ader was trying to condition taste-aversion in rats.

He’d give them a saccharine drink and, at the same time, inject them with Cytoxan, a drug that suppresses the immune system, but also makes you feel sick.

It worked. The critters learned to hate the sweet drink, which they linked with nausea.

But when Ader kept forcing the rats to drink it, they experienced something worse than a mere distaste for saccharine.

They started dropping dead, one by one.

The reason? Their immune system had “learned” to fail by repeated pairing of the drink with the cytotoxic drug. Incredibly, the drink alone turned off their immunity and they succumbed to infection.

Andrea Evers, Professor of Health Psychology at Leiden University, the Netherlands, is running a study that exploits this conditioning effect and may benefit patients with rheumatoid arthritis.

The immunosuppressant drug methotrexate is a common treatment for rheumatoid arthritis, a disorder where the person’s immune system attacks their own joints.

In Evers’ study, patients are getting methotrexate, but with a twist.

Instead of receiving the same dose each time, Evers is mixing it up, so patients get a higher dose followed by a lower dose.

The idea is that when the higher dose is given, the body links the pill with a damped-down immune system. When the lower dose is taken, the theory is it will work because the body has “learned” to curb immunity as a placebo response to simply taking the pill.

Results are pending, but Evers’ hope is that it will mean effective drug regimes that use lower doses with fewer side effects.

“There is no question at all that immune and endocrine parameters can be conditioned” says Evers, who has just published a meta-analysis of 16 studies in humans.

She found conditioning could reduce levels of the immune protein Interleukin-2, produce antihistamine effects in hay fever, and even alter insulin levels in diabetes.

But how does it work?

“Conditioning probably simulates the pathway of the original response of the medication. It duplicates the original response,” says Evers.

This is somewhat mind-contorting, until you think harder about Pavlov and his dogs.

After repeatedly having their meat snack announced with a bell, Pavlov’s hounds learned to drool just on hearing the bell. Over time, the bell, all on its own, could activate the unique physiology of the body’s salivation pathway.

Placebos, it seems, can work on the immune and endocrine systems with similar precision.

The medical profession, however, remains less than enthusiastic.

“I’m one of, I believe, two researchers in the country who speak on placebo, and I’ve been invited to one university to give a lecture at undergraduate level,” says Finniss, who will host an international placebo symposium in Sydney in November.

According to Charlotte Blease, a philosopher of science at University College Dublin, this antipathy may go to the core of what it means to be a doctor.

“Medical education is largely about biomedical facts. So called ‘softer’ sciences, such as psychology, get marginalised because it’s the hard stuff that is associated with what it really means to be a doctor,” she says.

The result, says Blease, is a large, placebo-shaped hole in the medical curriculum.

“There is a great deal of medical illiteracy about the placebo effect … it’s the science behind the art of medicine. Doctors need training in that.”

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