Placebo - an underrated treatment?

If you thought the placebo effect was all in the mind, think again.

A placebo is traditionally defined as a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect or in research, a substance that has no therapeutic effect, used as a control in testing new drugs.

For most of us, the potency of sugar pills is synonymous with the power of positive thinking; it works because you believe you’re taking a real drug. But new research continues to rattle this assumption and peel away further layers to the inner workings and potential therapeutic applications of the ‘powerful placebo’.

Most recently, researchers at Harvard Medical School’s Osher Research Center and Beth Israel Deaconess Medical Center (BIDMC) found that placebos work even when administered without 'deception'.

It is broadly understood that to prescribe a placebo openly as an actual treatment would risk undermining the effect. But data on placebos are so compelling that Harvard associate professor of medicine Ted Kaptchuk teamed up with colleagues at BIDMC to explore whether or not the power of placebos can be harnessed honestly and respectfully.

To do this, 80 patients suffering from irritable bowel syndrome (IBS) were divided into two groups: one group, the controls, received no treatment, while the other group received a regimen of placebos – honestly described as 'like sugar pills' – which they were instructed to take twice daily.

“Not only did we make it absolutely clear that these pills had no active ingredient and were made from inert substances, but we actually had ‘placebo’ printed on the bottle,” says Prof Kaptchuk. “We told the patients that they didn't have to even believe in the placebo effect. Just take the pills.”

For a three-week period, the patients were monitored. By the end of the trial, nearly twice as many patients treated with the placebo reported adequate symptom relief as compared to the control group (59% versus 35%).

Also, on other outcome measures, patients taking the placebo doubled their rates of improvement to a degree roughly equivalent to the effects of the most powerful IBS medications.

This particular aspect of their discovery has been mirrored in other studies and is proving quietly disconcerting for pharmaceutical companies who pour billions into developing lucrative new drugs only to find that, on occasion, the placebo group in their clinical trials fared just as well or even better than the active arm.

For a range of ailments, from pain and nausea to depression and Parkinson’s disease, placebos – whether sugar pills, saline injections, or sham surgery – have often produced results that rival those of standard therapies.

But, of course, there are limits to even the strongest placebo effect. No simulation could set a broken arm or clear a blocked artery. It can ease the discomfort of chemotherapy, but it won’t stop the growth of tumours.

For the most part, placebos appear to affect symptoms rather than underlying diseases, although sometimes, as in the case of depression or irritable bowel syndrome, there’s no meaningful distinction between the two.

For more than a decade, scientists have made tremendous strides in demonstrating the biological truth of the placebo effect. Numerous studies have shown that these inert pills can trigger verifiable changes in the body. The enduring search now is to uncover the precise mechanisms that elicit placebo-related effects, and to understand how these can be reliably harnessed.

Advances in image processing are aiding investigators in this quest. A study, published in Science in 2009, utilised functional magnetic resonance imaging (MRI) to scan the spinal cords of 15 healthy volunteers, homing in on an area called the dorsal horn, which transmits pain signals coming up through the spinal cord into the pain-related areas in the brain.

During the scan, the volunteers received laser 'pinpricks' to their hands. The volunteers were told that a pain-relief cream had been applied to one of their hands and a 'control' placebo cream to the other. But unknown to the volunteers, an identical 'inactive' control cream was administered to both hands.

When people believed that they had received the active cream, they reported feeling 25% less pain and showed significantly reduced activity in the spinal cord pathway that processes pain.

Previously, it has been shown that placebo causes the release of natural opioids in areas of the brain involved in pain control. 

“We’ve shown that psychological factors can influence pain at the earliest stage of the central nervous system, in a similar way to drugs like morphine,” said Falk Eippert, of the University Medical Centre Hamburg-Eppendorf, who led the study.

A world authority in this field, Fabrizio Benedetti, professor of clinical and applied physiology at the University of Turin Medical School, has devoted more than 15 years to mapping many of the neurobiological mechanisms of the placebo effect, uncovering a broad range of the body’s self-healing responses.

He says that placebo-activated opioids, for example, not only relieve pain, they also modulate heart rate and respiration. The neurotransmitter dopamine, when triggered by placebo treatment, helps improve motor function in Parkinson's patients. Mechanisms like these can elevate mood, sharpen cognitive ability, alleviate digestive disorders, relieve insomnia, and limit the secretion of stress-related hormones like insulin and cortisol.

Impressed by such findings, some researchers and clinicians hope to import them somehow from bench to bedside – adding placebo, in a structured way, to the doctor’s medical repertoire. But any attempt to harness the placebo effect immediately runs into problems. To present a dummy pill as real medicine would be, by most standards, to lie.

And yet, research has shown that many doctors incorporate the placebo into their therapeutic arsenal. For example, a 2004 study in the British Medical Journal found that 60% of doctors in Israel used placebos in their medical practice, most commonly to ‘fend off’ requests for unjustified medications or to calm a patient.

So if the medical profession see little harm in prescribing placebos, should they should be more widely available to the general public? After all, they are the ideal medicine: placebos typically have no side effects, are essentially free, and have clinical research to back up their beneficial effects.

Actually, a variety of placebo cures are available on the internet. One of the most popular is Obecalp, natural cherry-flavoured chewable tablets for children. Launched in 2008, Obecalp claims to be the first standardised, branded and pharmaceutical grade placebo on the market. Its name is ‘placebo’ spelled backwards.

The idea is a seductive one – to harness the placebo effect to comfort children who are a little unwell, without risking side-effects. They are designed for when 'children need a little more than a kiss to make it go away'.

However, Obecalp has received mixed reactions from the medical profession. One issue is that the pills will be used without medical supervision, creating a small risk that parents may delay bringing children with a serious illness to their GP because symptoms are masked for a while by the placebo effect.

Dr Clare Gerada, vice-chair of the Royal College of General Practitioners, described the pill as 'medicalising love'. Douglas Kamerow, associate editor of the British Medical Journal, highlighted a more serious threat. He pointed out in his editorial that by giving children a tablet for every ailment, parents may encourage them to think that popping a pill is the be-all and end-all of health.

“Sure, there are kids who end up wanting a colourful plaster for every ache and injury, but I have never seen an adult addicted to plasters. I have seen many adults who want a pill for every ill.”

But perhaps the real source of the placebo’s effect is the medical care that goes along with it, that the practice of medicine and the trappings of medical care is providing tangible healing influences.

For example, a study published in the British Medical Journal in 2008 described experiments conducted on patients with irritable bowel syndrome. Two groups underwent sham acupuncture, while a third remained on a waiting list. The patients receiving the sham treatment were divided into two subgroups – the first was treated in a friendly, empathetic way and the second group had their care delivered in a businesslike fashion.

None of the three groups had received ‘real’ treatment, yet investigators reported sharply different results.

After three weeks, 28% of patients on the waiting list reported 'adequate relief,' compared with 44% in the group treated impersonally, and fully 62% in the group with caring doctors. This last figure is comparable to rates of improvement from a drug now commonly taken for the illness, without the drug’s potentially severe side-effects.

The lead investigator was Harvard Medical School’s Prof Ted Kaptchuk. In this research, and his 2010 IBS study mentioned earlier, he emphasised that, rather than mere positive thinking contributing to the placebo effect, there may be significant benefit to the actual performance of the medical treatment ritual.

If this is true, then the takeaway message is not necessarily that doctors should be prescribing more fake pills but that as much thought should go into the medication selected as to the context in which it’s given.

Prof Anne Harrington

The definition of placebo effect has now broadened beyond dosing with inert pills to include questions about whether healing is still in part an ‘art’, and issues such as how the relationship between doctors and patients affects treatment outcomes.

At its best, that doctor-patient ritual activates positive expectations, triggers associations with past healing experiences, and eases distress in ways that can alleviate suffering.

Prof Anne Harrington, professor of the history of science at Harvard University and author of the book The Placebo Effect: An Interdisciplinary Exploration, suggests that a better way to think about the placebo effect would be as “the sum total of effects”.

Part of that experience might be going into a waiting room where the patient sees lots of certificates on the wall, and where a confident doctor walks in with a white coat that designates him as a professional expert. “All of these things produce the placebo effect,” she says.

Perhaps the secret of the placebo is rooted in the patient-doctor relationship. It may be about how people respond to symbols and about the intangible parts of medicine, such as the inherent capacity of human beings for self-healing.