Today’s Solutions: April 19, 2024

A sugar pill, a salt solution, a doctor in a white jacket–these all have the power to cure as long as the patient believes in their healing qualities. That seems impossible. So what does science say about the elusive placebo effect? And how can we use it to feel better?

Marco Visscher | May 2006 issue
When Judy Ruth Ashley came out of the local anaesthesia, she already felt better. She had gone to the hospital in Denver, Colorado, for an operation to help diminish the symptoms of Parkinson’s disease. The surgeon was to drill four holes in her skull through which he would implant fetal neural tissue into her brain, to stimulate cells to grow and develop, reversing the course of the disease.
Everything seemed to be going fine. In the months that followed her operation, the 65-year-old Ashley was less and less bothered by the dyskinesia—excessive, uncontrollable movement—that ruled her life for over 20 years. “I would wake up pain-free. I would get up and walk to the bathroom before I took any medication at all. I could run the vacuum, no problem, and I could even drive a car most of the time. Besides this, my blood pressure no longer dropped when I stood up. My speech was so much better I was able to sing again in the karaoke bar.”
But there is one remarkably enigmatic element of this success story: Ashley hadn’t received the neural implant at all. She was participating in a study into the effectiveness of the operation—but without knowing it, she was in the control group of people whose needles remained empty.
Conducted some 10 years ago, the controversial study is one of several involving sham operations [see box] and wide debate about the power of the placebo effect. How is it people get better after an operation that provides no active treatment? It figures as a spectacular example of the placebo effect, a phenomenon that has been known for centuries, but is still hard to grasp.
The placebo effect is the sudden healing of a patient through treatment that is not scientifically effective but works because the patient believes in it. A placebo—Latin for “I shall please”—is surgery or medicine that contains no active ingredients but promotes healing.
Doctors have been aware of the occurrence for centuries and have made conscious use of it to put patients at ease. When a patient would complain of vague symptoms, some physicians would pull out the “very special pill.” The patient believed it would work and complaints often disappeared.
Some say the history of medical science is the history of the placebo effect. Bloodletting is a well-known example. Until the 19th century, it was a commonly used technique that helped many people but as we all know, had no therapeutic effect—quite the opposite. Nowadays, every new medicine is officially tested against a placebo. It regularly happens that the sugar pill produces the same or better results than the medicine.
But how is that possible? How can people recover using a treatment that has no reason to work? Why did Judy Ruth Ashley’s condition improve even though she hadn’t had a real operation? In other words: What explains the placebo effect?
Ashley’s miraculous improvement seems to demonstrate that placebos are effective even in the operating room. In fact, the placebo effect may be much stronger in the operating room, according to Cynthia McRae, a health psychologist at the University of Denver who led the study[1]. “The more dramatic the medical intervention, the stronger the placebo effect will be. There is no doubt that brain surgery is much more invasive than taking a pill.”
That’s putting it mildly. Ashley’s husband remembers well what he thought when he watched as a frame was mounted on her head to make it easier for the surgeon to drill the holes in her skull. Monstrous!, he thought. Like medieval torture!
Of course Ashley knew she might get a sham operation. One year after the procedure, when it was revealed which patients had been given sham procedures, all were offered the chance to have the real surgery [2]. This had been a factor in Ashley’s decision to join the study. What did she have to lose? The alternative was inevitable mental and physical deterioration.
Ashley was one of 40 participants questioned by psychologists about their experiences and tested several times over the course of a year. The result? Patients who erroneously thought they had had a real transplant experienced a “better quality of life” and scored higher on physical tests than those who had really undergone the procedure, but believed they were the unlucky ones in the control group. The results of the study point to an unmistakable placebo effect.
Very little research has been done in this area of medicine. The pharmaceutical industry can’t profit; after all, they can’t make money from sugar pills. That is why many research funders look upon the placebo effect as an irritating variable in a study. It is often forgotten that the effect could help people and shave billions off spiralling health-care costs. If researchers could gain more insight into how the effect works, it would stand as one of the biggest medical breakthroughs in history.
Doctors rarely dispense fake pills today. Medical ethics and a new emphasis on a patient’s right to know make it almost impossible. Fake pills are only accepted by the established medical order for research purposes. Imagine a manufacturer has developed a new medicine. Before it can be sold, its effectiveness must be established. That’s usually done through a study in which a group of patients is given the new medicine and another group gets a placebo that looks, smells and tastes exactly like the real thing. The participants must have agreed to participate in advance. They are randomly assigned to groups and neither the researcher nor the patient knows who is getting the real pill and who is getting a placebo. This is called a “random double-blind placebo-controlled study”—which is what health regulators want to see. If the group receiving the test medicine reports better results than the placebo group, the medicine is approved for sale.
It sounds like a formality. After all, everything we think we know about medical science tells us that a medicine developed following years of research will score better than a sugar pill. Wrong! Research shows that both groups of patients usually report improvement.
Depending on the illness, at least 30 percent of participants, including those taking the placebo, report they feel better, and the numbers can go as high as 70 percent. Sometimes the medicine will do better than the placebo by only a couple of percentage points. For instance, the medicine may make 72 percent of the study’s participants better; a placebo, 70 percent. And you guessed it: The test medicine will generally be put on the market.
Moreover, it is not unusual that a placebo is more effective than the test medicine, which then likely disappears into the rejection pile.
But how does the placebo effect work? Some people are convinced that the effect proves that strength of mind is sufficient to heal the body. This argument holds that positive thoughts (hope, belief, trust) incite the body to destroy sick cells. The conviction is fueled by the vision that body and mind are one and not—as Rene Descartes reasoned in the 17th century—separate entities. Supporters of this vision challenge Descartes’ mechanical world view, which forms the foundation of modern science.
Other people remain skeptical, pointing out that there is no proof for the theory that the mind can heal. They wonder how the patient would feel if there hadn’t been any treatment at all. Maybe he would have gotten better anyway. After all, many health complaints simply disappear. People go to the doctor when their symptoms are at their worst and it’s only logical that they ease with time.
Yet that cannot explain Judy Ruth Ashley’s striking improvements. Brain cells slowly die off in patients suffering from Parkinson’s disease, a degenerative illness. If there is no effective treatment, the deterioration persists.
It has also been suggested that the placebo effect is triggered by a Pavlovian response. Just as the dogs in Pavlov’s famous experiment started drooling as soon as they heard the sounds that signalled feeding time, people might recover when a doctor gives them a pill as long as they have had a similar experience in the past. Testing with placebos on animals[3] supports this theory. When mice were given a sweet drink containing cyclophosphamide, a substance that suppresses the immune system, they became weak and nauseated. When given the sweet drink without cyclophosphamide, they showed the same symptoms.
But this theory also fails to explain why Ashley got better. After all, she had never had brain surgery before. How could she have exhibited a Pavlovian response?
Critics claim the placebo effect is only a short-term reaction. Indeed, most studies only last a few weeks and it is unclear whether the placebo group continues to report improvement compared with the group receiving the real medicine. But Ashley saw further progress many months after the sham operation. More to the point, her doctors—who knew she was participating in the study—were convinced their patient had been given the dopamine. Months later, when they adamantly claimed that any placebo effect from a sham operation would have long disappeared, they continued decreasing the dose of her regular medication, to half the original amount. (In 1997, two years after the sham operation, Ashley was given the real transplant. She continues to do well, under the circumstances.)
Placebos have a strong effect on patients dealing with pain. That became clear in World War II, when a continual shortage of morphine for wounded soldiers plagued the battlefields and hospitals. As long as wounded men didn’t know they were getting a simple saline solution, their pain eased.
During the 1980s, a study[4] provided definitive proof of this phenomenon. People who had undergone tooth extraction were told their pain would be relieved by a machine emitting ultrasonic waves. What they didn’t know was that the machine was switched off for half the patients. Afterwards, the participants reported on their pain levels. Compared with a third group of patients who had not received any treatment, those treated with ultrasound scored higher. It didn’t matter whether the machine was on or off.
Placebos have also been proven successful in treating depression, anxiety, stress, warts and ulcers—sometimes in as many as 60 to 70 percent of the cases. People report they feel better, their appetite has increased and their general sense of well-being has improved. Because these are subjective experiences, critics say it’s all psychological. But doesn’t that miss the point? Isn’t the ultimate goal of every treatment to help patients experience less pain and feel better?
There are, however, objective effects everyone can measure. Placebo treatments have been shown to lower blood pressure and cholesterol levels as well as improve reaction speeds, pulse rates and immune-system activity. In patients who are depressed, QEEG (“quantitative electroencephalogram”) equipment, also used to diagnose attention-deficit disorder, demonstrated[5] that their brain activity increased markedly after two weeks on a placebo.
Moreover, in one study, PET scans indicated[6] that patients with Parkinson’s disease were producing dopamine when given a particular medicine. Another group given a placebo showed the same result. The effect was brief; a temporary increase in dopamine in the brain doesn’t mean an automatic cure from the disease. Yet, Ashley saw improvement over one year, even after she knew she had received a sham operation.
Why are depression, anxiety and stress sensitive to the placebo effect? Perhaps, some claim, because these are the afflictions most receptive to personal attention. And attention is something many people miss from their family doctors. With the avalanche of new medicines coming onto the market in recent decades, the focus of doctors’ care has increasingly shifted from the patient to medical technology. Under increasing time pressure and often against their own wishes, doctors are now at the controls of a machine that is as detached as it is efficient. Patients get less attention than in days gone by.
That development has incited increasing numbers of people to seek help in the world of alternative and complementary therapies. Patient-satisfaction surveys consistently show that people are happier with treatment in the alternative sector. Why? Patients get more attention with alternative practitioners. People want a listening ear and emotional support, particularly when they are ill. But what they find at the doctor’s office is someone trained to assess patients critically, even skeptically. At the alternative practitioner’s office, they usually find someone who shows interest in them as people, exudes enthusiasm about the treatment and believes in what he or she is doing.
Could attention explain the placebo effect? In a placebo-controlled study, participants are given a lot of attention: They are asked questions about how they feel, someone listens to them, they have suddenly become important. This attention could be a vital contribution to feeling better, but it gives rise to yet another question: How could attention alone produce such strong effects?
Ultimately, the placebo phenomenon points to a strange paradox in modern medical science. As soon as an alternative-health treatment proves successful, it is dismissed as the placebo effect. It works only because people believe in it. Yet this explanation appears to contradict one of the foundations of medical science, which stresses that the mind and body are separate, therefore ruling out the possibility of healing through belief.
This blind spot exposes a painful reality in our health-care system. It is noteworthy that the debate over the ethics of placebos—Can patients be denied an effective treatment?—is conducted only by conventional-medicine practitioners. Sometimes that debate is a harsh one. Some argue placebo trials should be abandoned and pharmaceutical companies should find more responsible ways to test new medicines because patients may risk harm by being treated with inactive substances. Alternative practitioners are sometimes accused of endangering patients’ health by using unproven treatment methods.
Outside medical circles this is an irrelevant conversation. To the vast majority of the public, it’s more important that people get better than that their treatments be scientifically proven.
Placebos are not a solution for everything, but they do offer new opportunities for alternative-healing treatments. Various researchers have tried to determine whether a certain personality type is particularly sensitive or resistant to placebos. Those studies have produced uniform results. Everyone—men and women, young and old, the educated and uneducated—is sensitive to the placebo effect. It works on us all, even those who don’t believe in it. Some studies suggest, though, that a placebo effect is more likely to occur in people who are more optimistic than others and who have had positive experiments with medical interventions, thus expecting a treatment that will help them recover.
The personality of the doctor prescribing a placebo does, however, have an effect. Doctors who inspire trust, are optimistic, believe in their treatment, are clear in their diagnosis as well as being warm, sympathetic and involved, help stimulate a stronger placebo effect. Doctors can therefore become walking placebos themselves.
But the attitudes of patients matter too. Cynthia McRae, who led the quality-of-life study of Parkinson’s patients who received sham operations, believes that “the power of hope and optimism” should not be underestimated. The stronger the patient’s belief in the doctor’s authority, the greater the chance that the treatment will work, even when no active medicines are involved.
People would therefore be well-advised to look for a doctor who listens and in whom they have trust. Trust heals. Children know that. They totally trust everything will be okay when their mothers kiss their painful scraped knees.
Maybe that’s the perfect example of the placebo effect, as was true for Judy Ruth Ashley: healing through the kiss of grace.
References
[1] C. McRae, E. Cherin, et al.: “Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial,” Archives of General Psychiatry, 2004; 61: 412-20

[2] C.R. Freed, P.E. Greene, et al.: “Transplantation of embryonic dopamine neurons for severe Parkinson’s disease,” New England Journal of Medicine, 2001; 344: 710-719
[3] R.A. Ader, N. Cohen: “Behaviorally conditioned immunosuppression,” Psychosomatic Medicine, 1975; 37: 333-340
[4] I. Hashish, H.K. Hai, et al.: “‘Reduction of postoperative pain and swelling by ultrasound treatment: A placebo effect,” Pain, 1988; 33: 303-311
[5] A.F. Leuchter, I.A. Cook, et al.: “Changes in brain function of depressed subjects during treatment with placebo,” American Journal of Psychiatry, 2002; 159:122-129
[6] R. de la Fuente-Fernandez, T.J. Ruth, et al.: “Expectation and dopamine release: mechanism of the placebo effect in Parkinson’s disease,” Science, 2001; 293:1164-1166
[7] L.A. Cobb, G.I. Thomas, et al.: “An evaluation of internal-mammary-artery ligation by a double-blind technique,” New England Journal of Medicine, 1959; 260: 1115-1118
[8] J. B. Moseley, K. O’Malley, et al.: “A controlled trial of arthroscopic surgery for osteoarthritis of the knee,” New England Journal of Medicine, 2002; 347: 81-88
[9] T.J. Luparello, H.A. Lyons, et al.: “Influences of suggestion on airway reactivity in asthmatic subjects,” Psychosomatic Medicine, 1968; 30: 819-825
[10] L.C. Park, L. Covi: “Nonblind placebo trial: An exploration of neurotic patients’ responses to placebo when its inert content is disclosed,” Archives of General Psychiatry, 1965; 12: 336-345
[11] I. Kirsch, G. Sapirstein: “Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication,” Prevention and Treatment, 1998; 1: article 2a
[12] A. Khan, S. Khan, et al.: “Are placebo controls necessary to test new antidepressants and anxiolytics?” International Journal of Neuropsychopharmacology, 2002; 5:193-197
 

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