Though recurring tummy aches from irritable bowel syndrome are among patients' most common complaints, drugmakers have had trouble coming up with a safe and effective treatment. But in 2008 Harvard's Ted J. Kaptchuk devised a safe remedy that helps far more people than any designer drug ever did.
His magic cure: fake acupuncture delivered with lots of warm talk from a sympathetic acupuncturist -- but no needles. In a trial of 262 patients with severe IBS, 62 per cent of those who received the fake treatment got better, according to results published in the British Medical Journal. By comparison, only 28 per cent of a control group of patients put on a waiting list saw their symptoms improve markedly. A third group who got the fake acupuncture, but without any warm talk, showed in-between results: 44 per cent improved.
The result, says Kaptchuk, shows just how much the expectation of a cure -- and the rituals associated with medical treatment -- can improve real-world symptoms. "Our own will, imagination and belief can modulate the course of illness," says Kaptchuk.
Kaptchuk is among a small band of researchers studying the mechanisms behind the mysterious placebo effect. They are finding that the mere expectation that a treatment will help produces lasting effects on symptoms of many diseases -- and real changes inside patients' brains. Certainly placebos will never cure cancer or heart disease. But believing in a treatment may ease back pain, improve Parkinson's disease symptoms, alleviate depression and lessen nausea.
Mainstream medicine has tended to dismiss or ignore the placebo effect. Drug companies try to minimize it when conducting clinical trials. But Kaptchuk argues that doctors should instead do everything in their power to try enhance it by hyping up the rituals around their treatments. Doing so could help make existing treatments more effective and may reduce the need for expensive pills that have lots of side effects. "The ritual of health care has an important role to play that gets overlooked," says Kaptchuk.
Kaptchuk's research helps explain why doctors often think they have found a breakthrough treatment, only to find to their embarrassment years later that a placebo pill or other sham treatment works just as well. Knee arthroscopy was long thought to be a good treatment for arthritis pain. In 2002 a rigorous clinical trial found that patients got just as much relief from a fake surgery. Last summer two major trials tested vertebroplasty, a procedure to relieve pain from osteoporosis fractures by injecting cement into the back. Doctors had reported a high success rate. But it turned out that a fake surgery with no cement was just as good. It was all in the expectation.
The most recent big brouhaha is over studies in the Journal of the American Medical Association and PLoS Medicine finding that antidepressants barely beat sugar pills for mild and moderate depression. "The question is: Are we all fooling ourselves, telling ourselves that the improvement is caused by a pill when it's actually caused by the nice interaction we've had with our patients?" wonders psychiatrist and blogger Daniel Carlat. "A big part of what gets people better when they take pills is something other than the neurochemical action." Carlat thinks the pills work.
Kaptchuk, 62, has a college degree in religious studies from Columbia University and is one of the few Harvard medical professors without a Western graduate degree. An expert in acupuncture, he became interested in the placebo effect while getting a doctorate in Chinese medicine at the Macau Institute of Chinese Medicine in China in the 1970s (Massachusetts law doesn't allow him to call himself a doctor). He now leads a dozen investigators studying the placebo effect, funded with grants from the National Institutes of Health.
A placebo, he says, is the sum total of all the psychological benefits patients get from seeing their doctors and taking their pills. One theme of his research is that the bigger and more complicated the ritual, the greater the placebo effect. Surgery and medical devices often produce a bigger placebo effect than a pill because expectations for a cure are higher, he says. In a British Medical Journal article in 2006, for example, Kaptchuk and his colleagues reported treating 270 people suffering severe arm pain from repetitive-use injuries with either a placebo pill or fake acupuncture. The people who got the fake acupuncture reported significantly greater reductions in self-reported pain, even though there was no difference in posttreatment grip strength between the groups.
Certainly doctors and patients routinely underestimate how often symptoms will get better on their own. Back pain, irritable bowel syndrome, depression and anxiety tend to wax and wane over time. People report to the doctor's office when symptoms are worst. They assume the treatment they get is responsible for any improvement, even though they might have got better anyway. Some say this is not a true placebo effect.
But recent brain-imaging studies show that fake treatments can produce real effects deep inside the brain. One of the scientists performing these studies is University of Colorado psychologist Tor Wager, 35. Over the years "there has been tons of skepticism" that the placebo effect really exists, says Wager. He was skeptical himself when he first started doing brain scans of patients on placebos as a grad student at the University of Michigan. But now, he says, "the science has really exploded."
In recent years researchers have proved that the placebos alter the perception of pain inside the brain. The expectation of getting treated turns on the brain's reward system, causing the brain to produce dopamine and natural narcoticlike chemicals. This can trigger pain relief even in the absence of a drug. "The placebo effect is a real thing, and it is tied to an old, hardwired pain-control pathway," says Falk Eippert, a researcher at University Medical Center Hamburg-Eppendorf in Germany. "It is not some kind of elusive phenomenon."
In 2004 Wager and his colleagues applied an inert cream to the arms of 50 volunteers, then pressed a painfully hot ceramic plate against their arms while the subjects were inside a magnetic resonance imaging machine. Half the time the researchers lied to the subjects. "We told them it was a powerful pain-relieving drug," Wager says. The rest of the time they admitted the cream was inert. When volunteers thought they were getting a real drug, they reported 20 per cent less pain. Neuronal activity in regions of the brain that encode pain intensity subsided, the MRI showed.
The next year neuroscientist Jon-Kar Zubieta of the University of Michigan used a different type of brain scan (positron emission tomography) to delve more deeply into what goes on at the molecular level when people receive a placebo. He showed that when patients think they are getting a painkiller -- but are getting a placebo -- it stimulates some of the same molecular receptors in the brain that the narcotic painkiller morphine hits.
Another ailment where there is mounting evidence for a placebo effect is Parkinson's disease. In this disease dopamine-producing cells in the brain gradually die. A 2001 University of British Columbia study in the journal Science gave six Parkinson's disease patients a placebo and then examined their brains with positron emission tomography. The expectation of relief triggered large amounts of dopamine to be released inside the damaged areas of the brain.
Placebo is Latin for "I shall please," and for two centuries the word has been used to refer to inactive treatments given to make patients happy. The concept of a placebo effect was popularized in a 1955 JAMA article by anesthesiologist Henry Beecher, "The Powerful Placebo." It made a case for performing placebo-controlled trials of new drugs.
Some are still skeptics. Danish epidemiologist Asbjørn Hróbjartsson calls the placebo effect "grossly exaggerated." Hróbjartsson analyzed 202 studies comparing placebo treatments for various diseases with no treatment and found only a clear statistically significant placebo effect for two conditions: pain and nausea. He says a lot of what gets called the placebo effect is really patients getting better on their own or exaggerating symptom improvements to please their doctors.
While drug companies are desperate to get rid of the placebo effect, the opposite is true in clinical practice. A 2008 survey of U.S. internists and rheumatologists found that half of them prescribed placebos, including sugar pills, vitamins and supplements they did not expect to have an effect on anything aside from the patient's own belief. But it may be possible to enhance the placebo effect even when active drugs are being used. "We do a lot to undermine the placebo effect" by making pill-taking mechanical, argues Duke University behavioral economist Dan Ariely. In a 2008 experiment he found that more people get pain relief from a placebo that supposedly costs $2.50 a pill than from a placebo they think costs only 10 cents per pill.
To enhance patients' expectations, drugs could come in colorful packaging instead of plain white bottles, says Ariely, author of Predictably Irrational. The term "generic drug" should be abandoned because it is associated with cheapness, he says. Ariely became aware of the placebo effect after suffering severe burns in an explosion. At the hospital he was at in Israel, morphine doses were limited to prevent addiction. Sometimes patients exhausted their daily rations and would be crying in agony. "The nurses would give them a placebo injection, and they would go to sleep. It was unbelievable," he says.
Another possibility: It may able be possible to take advantage of the placebo effect to lower the amount of drug needed to treat a patient. This could save money and prevent side effects. Only a handful of small studies have explored this concept. In one trial of 46 psoriasis patients, psychologist Robert Ader from the University of Rochester School of Medicine & Dentistry found it was possible to reduce the amount of steroids needed to treat psoriasis by half, giving patients the full dose of steroids some days and a placebo cream on others. "The brain interacts with the immune system in all sorts of ways -- there are communications in both directions," Ader says.
It could take decades for researchers like Kaptchuk and Wager to parse all the psychological and neurobiological mechanisms behind the placebo effect. They may never come up with a clear answer as to what is going on. Meanwhile, the next time your doctor recommends an expensive drug or complicated operation to relieve everyday symptoms, it may pay to ask him a simple question. Will the treatment beat a placebo?
