In randomized, controlled clinical trials, participants are given an active drug or a placebo—a “sugar pill.” The expectation is that the active drug will produce a beneficial effect while the placebo will cause no effect. What’s lost in these investigations is that the placebo has power of its own. We know is that there is a documented “placebo effect,” which happens when some people respond to a placebo even though it provides no actual medicine. This effect has been thought to be largely due to people’s beliefs or expectations that they are getting the real treatment and not the fake one. But recently, researchers have come to realize that the placebo effect is not just a psychological response, but a physiological one as well. Scientists are now studying the biological mechanisms that underpin the placebo effect. In one study, for instance, investigators used functional MRI to map the area in the brain where the placebo effect occurs. But, there is much more to learn about the powers of the placebo effect. The placebo effect is real The placebo effect is more than just wishful thinking. People taking a placebo can demonstrate measurable physiological changes akin to those taking effective medications. Investigators have observed improvements in blood pressure, heart rate, and blood test results in some research participants who responded to a placebo. “Such basic mechanistic discoveries have greatly enhanced the credibility of placebo effects,” co-wrote Ted J. Kaptchuk, professor of medicine, Harvard Medical School, and director of the Harvard-wide Program in Placebo Studies and the Therapeutic Encounter, Beth Israel Deaconess Medical Center, Boston, MA. “Moreover, recent clinical research into placebo effects has provided compelling evidence that these effects are genuine biopsychosocial phenomena that represent more than simply spontaneous remission, normal symptom fluctuations, and regression to the mean.” Placebos may not cure, but they can improve symptoms While placebos rarely cure, they can provide symptomatic relief. “Although research has revealed objective neurobiologic pathways and correlates of placebo responses, the evidence to date suggests that the therapeutic benefits associated with placebo effects do not alter the pathophysiology of diseases beyond their symptomatic manifestations; they primarily address subjective and self-appraised symptoms,” Kaptchuk wrote. Placebos can’t shrink a tumor, for example, but some researchers have shown that cancer symptoms and side effects—like fatigue, nausea, hot flashes, and pain—are responsive to placebos. The placebo effect is strongest in the United States Researchers have found that the placebo effect is growing stronger—but only in the United States. In a meta-analysis of 84 clinical trials of pain medications, researchers found that the symptomatic effects of the medications stayed the same over a 23-year period, but placebo responses rose. In fact, the placebo response nearly equaled that of the medication effect—such that pharmaceutical companies are finding it harder and harder to prove that their pain medications work better than placebo. Moreover, this effect was only found in clinical trials performed in the United States. What’s going on? Scientists have two theories. One is that direct-to-consumer drug advertising (which is only allowed in the United States and New Zealand) increases patients’ expectations that the medication will work, which may translate into a stronger placebo effect. The other theory is that larger, more expensive, and more elaborate clinical trials—which are more common in the United States than in other countries—create higher expectations in trial participants, resulting in a bigger placebo effect. Providers boost the placebo effect As the two theories discussed above suggest, the person providing the placebo and the environment in which the placebo is given have meaningful influences on the placebo effect. “In a broad sense, placebo effects are improvements in patients’ symptoms that are attributable to their participation in the therapeutic encounter, with its rituals, symbols, and interactions,” wrote Kaptchuk. “This diverse collection of signs and behaviors includes identifiable health care paraphernalia and settings, emotional and cognitive engagement with clinicians, empathic and intimate witnessing, and the laying on of hands.” In one study, researchers found that just a physician’s reassuring words could provide symptomatic improvement. In this way, physicians can turn the placebo effect to their advantage, suggested Alia J. Crum, PhD, assistant professor of psychology, Stanford University, and principal investigator of the Stanford Mind & Body Lab, Stanford, CA. “We’re talking about simple inexpensive interventions, changes in our words and actions that can produce objectively better health outcomes,” she explained in a TEDMED Talk. “The effects of the forces underlying placebo effects aren't irrelevant. They are alive and at play in every single medical encounter for better or for worse.” The ‘nocebo’ effect works, too The placebo effect can be beneficial to the patient but, when used negatively, it can undercut and worsen the patient’s response. This is called the nocebo effect. Think about a commercial or ad for a drug: “May cause headache or nausea.” How many people who are eventually prescribed that drug consequently report those exact adverse effects? “Not infrequently, patients perceive side effects of medications that are actually caused by anticipation of negative effects or heightened attentiveness to normal background discomforts of daily life in the context of a new therapeutic regimen,” Kaptchuk explained. Researchers have shown that when people are told that an effective drug (in this case, a proven analgesic cream) can worsen their symptoms instead of improve them, they report more symptoms of pain. An ‘open-label’ placebo is still a placebo Historically, the placebo effect depends upon deception—that the person who receives the placebo must be unaware of its true, inert nature. If people are told outright that they are receiving a placebo, then surely the placebo will have no effect, right? Apparently not. Kaptchuk and his team have shown that deception isn’t necessary to achieve the placebo effect. In one study involving people with irritable bowel syndrome (IBS), one group was told they were getting a placebo (which Kaptchuk calls an “open-label” placebo) and the other group received nothing at all. The placebo group demonstrated dramatic and significant improvements in their IBS symptoms, despite knowing they received a “sugar pill” without any active medication. “People can still get a placebo response, even though they know they are on a placebo,” Kaptchuk said. “You don’t need deception or concealment for many conditions to get a significant and meaningful placebo effect.” Most is still unknown Consider, for a moment, the tens of thousands—perhaps hundreds of thousands—of clinical trials that have compared an off-the-shelf placebo pill against a drug that took years of development. The investigators studied and tested the trial drug backwards and forwards, yet they know very little about the placebo. And there’s much more to learn about it. “We used to think the placebo effect was limited to suggestible people without ‘real’ disease; we now know better. But there is plenty that remains mysterious. We don’t know how to predict who will respond well to a placebo or how to reliably harness its power,” wrote Robert H. Shmerling, MD, on the Harvard Health Blog. “Still,” he added, “the day may come when the placebo effect is better understood and, under the right circumstances, used effectively in clinical practice. Given that many people either don’t improve with standard medications or have bothersome side effects, that day can’t come soon enough.” Source
