Mind over matter
Placebos help crack open the window to our natural mind-body connections
By Joan Trossman Bien 03/31/2011
How would you feel if you learned, after the fact, that your doctor had used a placebo in your treatment and it worked? Would you have wanted to know that your own brain had helped to heal you? Or would you have considered the action one of deception and disrespect? Would you feel diminished as a patient or empowered? These questions are at the heart of new discoveries about the potency of the placebo effect and how to harness its ability to heal.
The word placebo is Latin for “I shall please.” The medicinal use of placebos goes back at least as far as the 1700s. During those times, bleeding and purging a patient were common treatments for a variety of ills. It has been agreed that George Washington died at the hands of his physicians. He had complained of a sore throat, and three different doctors in succession proceeded to “bleed” Washington. He died, in large part, from exsanguination. At about the same time, a medical dictionary published in 1811 defined placebo as “an epithet given to any medicine adapted more to please than benefit the patient.”
This line of thinking changed after World War II, when drugs that actually cured diseases emerged. Along with this change came the social rearrangement of the doctor and patient relationship. Instead of the paternal physician, the patient acquired new rights, including the right to understand and consent to the treatment.
In 1955, a paper by Harvard anesthesiologist Henry Beecher said the placebo effect was so powerful that it must be considered in research and when testing new drugs. Today, taking the placebo effect into account has evolved into randomized clinical trials or the double-blind study.
In a double-blind study, the participants and their health care providers are separated into groups. One group receives the active drug that is being studied for efficacy and safety. The other group receives a placebo, a pill or other medical treatment that does not have the active ingredients of the drug. Neither providers nor participants are told which group they are in. When the trial is finished, the results are compared. If the participants who received the active drug fared better in statistically significant numbers, over and above those who received the placebos, then the drug is shown to be effective. Similarly, side effects are also evaluated.
Thus, the placebo effect is often seen as benign and merely something that may interfere with the pharmaceutical company’s goal of proving the value of its new drug. Recently, studies have found the placebo effect to be more powerful and more complicated than had been previously believed. These studies have opened the doors to myriad possibilities and uses for the placebo effect. Instead of the placebo just being the foil for a drug’s effectiveness, the placebo effect itself is being studied.
Your brain on placebo
Researchers have looked at and recorded specific brain activity under a variety of circumstances. According to the American Cancer Society, one study found that when the patient believes the substance will work, “the patient’s mind somehow causes short-term physical changes in the body.” Researchers say the positive effect of the placebo may be due to release of the feel-good hormones, endorphins, in the brain.
The expectations of a patient, however, are often colored by personal experiences. Another study cited by the American Cancer Society involved Alzheimer’s patients. In that case, when the participants were given doses of actual pain medication, they felt less reduction in pain than would have been expected. The Alzheimer’s patients may have required higher doses of the pain medication, possibly because they forgot they were getting the drugs or perhaps they had forgotten that the pain medication had worked for them previously.
Barbara Blume is a clinical psychologist who works with neurofeedback, a sophisticated but noninvasive method of changing the brain in order to accomplish such goals as reducing the effects of ADHD, getting rid of insomnia and various other uses. The process is laborious and expensive but it has been proven to work for conditions that otherwise are incurable.
Blume has not found the placebo effect to be useful in her practice. “Neurofeedback measures electrical pathways of the brain. As such, there is great importance in my field in quantifying scientific data. I believe the placebo effect can be measured at the moment, but the effect is transitory and does not result in long-term changes,” Blume said. “However, in the documented case of Buddhist monks who meditate 24/7, it has been shown that they have a perfectly sculpted brain as measured by the functional MRI.”
Recent studies have also revealed the dark side of the placebo effect. John Davis has been a professor of neuropsychology at McMasters University in Ontario, Canada, for nearly three decades. He explained the nocebo effect, which is the manifestation of negative expectations for a treatment, “an interesting twist to the study of the nocebo effect, sort of the evil twin of the placebo. If an expectancy is induced so that a patient believes that a treatment is inert or harmful (when it has been shown to be beneficial), then the treatment’s effect is less than it normally is.”
This was shown in a recent study of brain imaging by Oxford University. Patients who had doubts about the effectiveness of a strong pain medication actually experienced less relief because the negative expectations were able to override the benefits of the drug.
In that study, volunteers were set up with intravenous lines while placed in MRI scanners. Heat was applied to their leg just to the point where it became painful. The participants were not told when doctors administered pain-relieving drugs. At different points in the test, the patients rated the amount of pain they were experiencing. Their responses were tied closely to what they were told by the doctors, whether the drug was being administered or shut off. Sometimes the doctors told the truth. Sometimes they lied. This expectation of what they thought they should be feeling had a greater effect on the volunteers’ perceptions of pain relief than did the actual drug. For example, when falsely told that the drug had been discontinued, their pain rating went up.
The advice from the leader of this study was a warning that doctors should not underestimate the power of the patient’s expectation of a particular outcome.
Harvard University researchers discovered a new dimension to the placebo effect that may open the door for treatments in the future. A group of 80 patients with irritable bowel syndrome (IBS) was divided into two groups. One group received no treatment at all. The other group received a placebo, inert pills that were to be taken twice a day. The patients were told that the pills were dummy pills, and the word “placebo” was written on the pill bottles. The patients were told they did not need even to believe in the placebo effect.
The results: patients receiving the placebos had a positive response to the pills when compared with the group that was given nothing at all. Improvement was shown at the halfway point and also at the conclusion of the study.
The real surprise of the study was that patients on the placebo had doubled their rate of improvement when compared to that achieved with the most powerful IBS treatment. This was actual proof of mind over matter and a patient’s ability to improve his or her condition. It also demonstrated that when a patient deeply believes and expects a treatment to be effective. This belief can enhance the benefits of an active drug.
A groundbreaking study at UCLA, looking at depression and placebos, questioned the effectiveness of commonly prescribed antidepressant medications. Dr. Andrew Leuchter, a professor of psychiatry for human behavior and neurosciences at UCLA, participated in this study. Leuchter said his studies are trying to decipher what happens in the brain during the placebo effect.
“Antidepression medications are very good, but placebos aren’t bad either,” Leuchter said. “There are a lot of patients who get placebos who have depression and get better, at least transiently. Not everybody. It’s really a minority of patients with depression who get better with placebos, but some of them do get significantly better. We found that there were certain genetic differences between individuals who got better with placebos and those who did not.”
Leuchter has also seen patients experience the nocebo effect in an unexpected manner. “About two-thirds of the patients who take placebos get side effects,” he said. “They are the same side effects that are listed in the consent form for the study.” Informed consent is required for participation.
“I had one gentleman in a study of an experimental medication, and he came in complaining bitterly about the side effects,” Leuchter said. “He said, ‘This drug is terrible! The worst thing ever! I’m going to call the FDA and tell them they should pull the plug on the study.’”
Leuchter said the patient requested to be released from the study. “We let him out, of course,” he said. “Before they leave, we break the blind and tell them what they were getting. I was flabbergasted that he was getting placebos, he was so sick.”
Placebos are a crucial element of proving a new drug’s efficacy and safety. Randomized controlled clinical trials are necessary for an accurate evaluation of the drug’s performance.
Steve Snapinn is the vice president of biostatistics and epidemiology for Amgen in Thousand Oaks. While acknowledging the importance of placebos in double-blind studies, he questions whether the placebo effect really exists.
What is really happening, according to Snapinn, is the statistical phenomenon called “regression to the mean.” This refers to the normal ebb and flow of symptoms in most diseases. Some days will show improvement and other days will show the disease progressing.
Snapinn said that in a drug trial for a treatment for anemia, a condition that is determined by a low hemoglobin count in the blood, the majority of patients receiving a placebo will experience an increase in hemoglobin concentration.
“This improvement in clinical outcome following the administration of a placebo is often interpreted to represent a beneficial biologic effect of the placebo itself,” Snapinn said. “However, I seriously doubt the existence of a placebo effect by this definition. Instead, what appears to be a biologic effect of the placebo can be explained by regression to the mean.”
Snapinn said that the fluctuation of any disease that is being studied will always be a variable in a double-blind drug study and must be factored into an analysis of the results. “Whether the placebo has a real biological effect, or whether it’s the statistical phenomenon of regression to the mean, these clinical improvements seen in patients receiving placebo are very important to consider when evaluating the results of our clinical studies,” he said.
“If we simply looked at the average improvement in clinical outcomes after patients received the new therapeutic, it would be impacted by this phenomenon, and we would get an inflated view of the effect of the treatment,” Snapinn said.
The doctor’s dilemma
In light of the recent studies that have shown the power of the placebo, physicians are faced with the moral question: When is it ethical to use placebos as treatment?
The placebo effect has been shown to be helpful, it costs nothing, and it has no actual side effects. Or would placebos merely mask the symptoms, fail to improve the underlying condition and delay more meaningful treatment? Is deception acceptable in order to help a patient improve? Is deception a necessary element of effective placebo use?
According to a recent survey published in the British Medical Journal, about half of American physicians use some form of placebo. Although only a few actually use dummy pills, many more prescribed treatments that were not shown to have a beneficial effect on the condition and were used as placebos.
Leuchter acknowledged that the placebo effect is a problematic issue in the testing of new drugs. “However, in clinical medicine, the placebo response is really our friend because whatever it is that helps patients get better is something that we want to encourage and want to try to take advantage of,” he said.
As for pharmaceutical treatments, Leuchter believes that it is only part of the cure. “We have this illusion that things are about molecules these days,” he said. “The placebo response really disabuses us of that. In some ways, it is kind of a humbling experience. Even if we understood the totality of somebody’s genetic makeup and measured all of their hormonal levels, the chemistry of their brain, the structure of their brain, still there is something about the individual’s experience.”
There are two goals that are the basis for Leuchter’s research. “We would like to be able to use this information to understand how it is that people get better from whatever you are treating them for,” he said. “The placebo is really the only scientific way to get at why it is that people get well because you’re giving all the trappings of treatment except for the active ingredient.
“The second thing that we would like to be able to do is enhance treatments in general,” Leuchter said, “help medical treatment work better. The first step, then, would be for the physician to ask the patient how they are doing that day and what’s their expectation coming in to see you.”
Leuchter said this could only happen in a perfect world, where insurance companies did not financially punish doctors who took more time to discuss these issues with patients and, instead, reward providers who see the highest number of patients.
The placebo was once relegated to the role of making drug trials more difficult to assess. But now it is being studied as a tool to enhance medical treatment and even as a complete treatment. The window to the human mind is cracking open just a bit wider as traditional medicine reconsiders the value of the placebo and of other mind-body connections as legitimate and useful aids in treatment.