If illness can come on suddenly and mysteriously, why not the cure? It's time we learned to harness the PLACEBO EFFECT

My general practitioner has a great bedside manner. She'll pat me reassuringly on the arm or sit beside me on the examining table to discuss my problems eye to eye. No matter what chaos is unfolding in her waiting room, she's never too rushed to explain the details of a treatment. But when I recently asked Dr. Gregory about her thinking on placebos, she bristled.

"I have a problem with administering a placebo," she said. "I'm a very straight-forward person, an honest person. Giving a placebo isn't exactly dishonest, but it doesn't suit my personality. I'm not going to give somebody something and say it's medicine when it's not."

For many doctors and patients alike, the word placebo--from the Latin for "I shall please"--gives off the scent of snake oil and conjures up images of quackery and deceit. Since the early 19th century, placebos have been described in medical dictionaries as inert, inactive substances with no intrinsic therapeutic value, "given more to please than to benefit the patient." With few real medicines or procedures in their satchels before the age of antibiotics, physicians would parcel out colored sugar pills, bread pills, salt water injections and more elaborate subterfuges, their goal to soothe the patient while waiting for the problem to heal on its own.

Medical historians estimate that until World War II, as many as 80 percent of prescriptions were placebos, whether physicians knew it or not. According to Ted J. Kaptchuk, O.M.D., associate director of the Center for Alternative Medicine Research at Harvard Medical School and author of a history of the medical use of placebo, most doctors were quite comfortable with what they viewed as a benevolent deception. "They thought of it as a way of dealing with difficult patients," says Kaptchuk. "Doctors knew it did something, and they would dispense placebos for problems they had no answer for."

In recent years, however, there have been major revisions in medical thinking about placebos. Now medical researchers recognize that the placebo effect, which comes about from more than just swallowing a sugar pill, can actually be a boon to patients' healing. The new definition of placebo is that the sum of all the interactions between patient and physician, including such non-quantifiable variables as the doctor's empathy, enthusiasm and prestige; the patient's hopefulness, commitment and trust; and the drama surrounding examination, diagnosis and treatment.

Tens of thousands of studies point to the same conclusion: Ultimately, no one really knows what heals people--whether it's something outside of them or deep within. Across the board, placebos work as effectively--and in many cases, more effectively--than the drug or procedure being tested. And to many minds, that begs the question, Why not study this mysterious placebo effect and learn to harness its potent healing powers?

Injections of Hope
Consider this scenario: Melissa L. has just spent half an hour being palpated and probed, answering a stream of questions about her health history and the stomach pain that has been plaguing her for months. As the doctor, a well-known expert in his field, makes some notes, Melissa gazes around the room at the impressive framed diplomas and awards. "I'm going to advise a series of injections," the doctor then says, looking straight into Melissa's eyes. "They have helped many other patients, but I cannot explain why they work and can't promise that they will work. Many people tell me they feel better and healthier afterward, and I hope you will, too."

Melissa has just been invited to partake of the power of the placebo. If she accepts the treatment, the odds are firmly in her favor that she will lose her pain, even if the actual injections play only a small part. More significant to the healing process will be her doctor's conviction and stature, combined with her own hope and positive expectations.

If Melissa does get relief from a placebo, does that mean her pain was imaginary? Not at all. Over the past 50 years, there has been vast research showing that placebos can alter measurable bodily activity, including blood pressure heart rate, gastric secretions and immune system function.

Indeed, the placebo effect can be superior to that of standard drug therapy. For example, in a 1999 analysis of two PMS studies, 20 percent of women on placebo therapy for severe PMS showed significant and sustained improvement of symptoms, while another 42 percent experienced partial improvement--both better results than achieved with hormones or antidepressants.

Back in the mid-1950s, a landmark study by Harvard anesthesiology professor Henry K. Beecher, M.D., led to his estimation that placebos could bring relief to an average of 35 percent of those who suffered from pain, high blood pressure, asthma, cough, headache and angina pectoris. The medical community was galvanized by these findings, but oddly, not enough to examine the placebo effect itself. Instead, researchers decided to measure new drugs and therapeutic approaches against placebos in order to give the drugs scientific credibility. (It's hard to believe today, but according to historian Kaptchuk, therapies developed before 1950 made their way into medicine based on the clinical impressions and recommendations of leading physicians, with little, if any, controlled evidence.)

Thus, every new drug introduced in the past 40 years has been compared with placebos in double-blind, randomized, controlled trials. For a drug to pass muster with the Food and Drug Administration (FDA), its effects must be demonstrated to be superior to that of the placebo. Often that doesn't happen, and the usual consequence is that the drug is revamped--or scrapped altogether. But wouldn't a more productive follow-up be to study the mechanism of the placebo effect itself?.

Mind Matters
In conventional medical wisdom, one explanation for the placebo effect is that taking a placebo stimulates the release of endorphins, the body's natural painkilling hormones. Yet that connection doesn't answer why placebos are effective for asthma, skin disease and other non-pain-related ailments. (Let alone how an inert substance can trigger the release of brain chemicals in the first place.)

The newest theories on why placebos work focus on expectation and behavioral conditioning. Expecting to get better actually helps you get better, say researchers. Having been helped by a doctor once makes it easier for you to "allow" yourself to be helped by a doctor again. And having your pain relieved by medication makes it more likely that taking another pill, even a placebo, will lessen the hurt. Placebos have "time-effect curves" just like real drugs: That is, they're most effective for the first few hours after you take them, then they begin to wear off. And taking two placebos, like taking two "real" pain pills, provides stronger benefits than taking just one.

As for conditioning, your body can be trained to respond to a neutral substance just as readily as Pavlov's dog learned to salivate without food. In a classic study at the University of Rochester in the mid-1970s, lab mice were injected with a drug to suppress their immune systems and simultaneously fed saccharine-flavored water (mice are apparently very sensitive to the flavor of saccharine). After a period of time, when the mice were fed the flavored water without the injection, they still exhibited a drop in their immune functions.(*)

Mysterious Ways
To encourage doctors and patients to realize the value of the placebo effect, it may be time to retire the phrase itself, suggests Walter A. Brown, M.D., clinical professor of psychiatry at Brown University's program in medicine. After all, the word carries a stigma, when in practice it's a fact that symptoms can be eased by all sorts of "responses to the healing situation," as Brown puts it.

After studying the placebo effect for nearly 20 years, Brown has recognized that the simple act of seeking treatment--visiting a medical expert or taking a pill--helps patients recover, "I've become increasingly aware of how reassuring a doctor can be--how important what I say to a patient is and how important something as basic as an evaluation or diagnosis can be," he says.

He's also noticed that physicians are becoming more open to the notion of the placebo effect. Part of their renewed interest in the long-known phenomenon can be attributed, he believes, to a growing confidence in standard medical procedures. "Now that medicine is more scientific," Brown says, "scientists can be more accepting and less defensive about aspects of healing that are somewhat mysterious."

The popularity of alternative medicine--to some old-school physicians, the ultimate placebo--and newfound understandings of the mind/body connection have also helped. Indeed, the new field of psychoneuroimmunology, the study of how thoughts and emotions affect the immune system, is flourishing in universities and medical centers.

Brown thinks that even though most physicians aren't quite ready to honestly present their patients with the option of taking a placebo, they may be more willing to hedge a little. "I think that the most likely scenario is for practitioners of traditional medicine to provide or recommend one of the alternative medicine therapies, even though they believe it may not have intrinsic value," he says.

Others believe that the placebo effect has a chance to come further out of the (medical) closet. In a 1998 article in the Journal of the American Medical Association (JAMA) predicting medical changes in the new millennium, Thomas Delbanco, M.D., professor of medicine at Harvard Medical School, forecasted that doctors will dispense placebos without apology As he put it: "They will simply tell their patients, 'This is a placebo. We have little idea right now why it works, but it often does. Give it a try.'"

Healing Encounters
Even if doctors are ready to "exploit" placebo power, will patients be willing to trust the healing encounter as much as they've trusted specific pharmaceuticals in the past? Brown thinks so. "Patients who go to doctors don't want to decide what kind of treatment they should get," he says. "They certainly want options, but when people are sick and frightened, they want to be in somebody's hands. They want guidance."

In The Power of Hope (Yale University Press, 1998), gastroenterologist Howard Spiro, M.D., professor of medicine and director of the Program for Humanities in Medicine at Yale University School of Medicine, makes an eloquent case for harnessing the placebo effect. "When I say that something is a placebo, that doesn't mean I disparage it," he says. "Clearly placebos work in 30 to 60 percent of patients who have problems of certain kinds. They are powerful agents and testify to the ability of one person to help another."

But placebos are not cure-alls, Spiro cautions. "When you have a strong syndrome due to a tumor in the pancreas, all the wishing in the world won't change it," he says. "I can't find evidence that placebos help cancer." (For a dissenting opinion, see "The Perhaps Apocryphal Tale of Mr. Wright," p. 78.)

A New Mindset
As doctors begin to better understand the placebo effect, one positive benefit may simply be that they improve their bedside manners--and that alone can have a huge placebo effect.

"If you ask Yale pre-med students what they'd tell a man whose liver is ruptured and while being taken to the operating room, asks, 'Doc will I make it?' pre-meds say, 'Yeah,' and give lots of reassurance," Spiro recounts. "But after three years in med school, they give only weaselly reassurance. They've become afraid to be therapeutic. That's because they've learned to be more cautious, learned the value of truth-telling and no longer recognize that truth is relative. Patients want, more than anything else, hope, reassurance and comfort."

Physicians increasingly are being encouraged to remember that their prime role is to deliver that comfort. In the pages of a 1996 British Medical Journal, doctors were urged to "say more useful things to patients in better ways." In a 1994 issue of JAMA they're reminded that "warmth, friendliness, interest, sympathy, empathy ... and positive attitude toward the patient and toward the treatment" will lead to better health care.

"To harness the power of placebo, physicians will need to be less arrogant about their own therapies and understand that the therapies are only a small part of what they can give patients," says Kaptchuk. Until then, it will best serve your health to choose doctors you can trust, and trust the treatments they provide.

Whether you've been prescribed the most powerful antibiotic available or "Obecalp" (placebo spelled backward, it's the generic name for "inert" pills), your healing process can be significantly enhanced by the placebo effect. Here's how to give your treatment a boost.

Choose a doctor you really, really trust. Studies show that a doctor's attentiveness, thoroughness and willingness to listen increase the benefit of any given therapy. Patients who feel rushed through their exams or anonymous in their medical encounters do not thrive. "A doctor," says Howar Spiro, M.D., professor of medicine and director of the Program for Humanities in Medicine at Yale University School of Medicine, "helps simply by giving courage, giving hope and being there with the patient."
Seek treatment of some sort. Placebo power begins to take effect even before you enter a doctor's office, says William A. Brown, M.D., clinical professor of psychiatry at Brown University's program in medicine "If patients have a symptom that has been a source of concern, they begin to feet better as soon as they decide to seek medical treatment." Effective as some of today's medicines are, a number of studies show that taking prescribed pills regularly and on time--whether a "real" drug or a placebo--reduces symptoms.
Let your healer be the boss. It's necessary and useful to be aware of the options for treatment and the reasoning behind your doctor's prescriptions, but sometimes patients can overcontrol the doctor-patient relationship. Clinging to control can heighten anxiety and disrupt the healing alliance. If you've done your prep work and found a physician you can trust, then trust him or her. Part of your cure is giving over part of the responsibility.
The Nocebo Effect
If positive messages and expectations can make a patient better, it stands to reason that negative messages and expectations can make a patient worse.

Nocebo, a term coined by a medical researcher in the early 1960s, is placebo's evil twin. Its dominant qualities are fear, anxiety and mistrust. At the outer limits of nocebo is the voodoo curse, in which belief in "imaginary" forces and the power of the (witch) doctor brings on sickness or death.

In the world of modern medicine, nocebo, like placebo, works in much subtler ways, but it's creeping into insurance and malpractice proceedings. For obvious ethical reasons, it's difficult to put negative medical treatment to the test, but there has been plenty of observation and some carefully handled research.

In one much-quoted study, a physician randomly assigned patients with generalized aches, pains and fatigue but no specific diagnosis to one of two encounters. The "positive" patients were given a diagnosis and told they would be better in a few days. The "negatives" were brushed off, the doctor telling them he didn't know what their problem was.

After two weeks, 64 percent of the positive group had gotten better while only 39 percent of the negative group had an easing of symptoms. The remaining 61 percent of the patients in the negative group, whose symptoms remained unchanged, are viewed as a product of the nocebo effect.

The Perhaps Apocryphal Tale of Mr. Wright
First recounted at a national medical symposium and first published in The Annals of Internal Medicine in 1964, the perhaps apocryphal story of poor "Mr. Wright" is one of the most famous exemplars of both placebo and nocebo effects. "This report has been accepted unchallenged to a mind-boggling extent," says Howard Spiro, M.D., professor of medicine and director of the Program for Humanities in Medicine at Yale University School of Medicine, "but it's easy to see why people would want to believe in it."

This is how it goes: Stricken with advanced lymphatic cancer and given but a short time to live, Mr. Wright was hospitalized in Long Beach, Calif., when he read about an experimental serum called Krebiozen. Though his advanced disease should have made him ineligible for drug trials, he pleaded so strongly that he was included in the testing. A single injection on a Friday afternoon led to astonishing results. By Monday, Wright was out of his "death bed," cheerfully walking about. His tumors had shrunk by half.

But Wright's response to the serum was an anomaly, and medical reports reached him suggesting Krebiozen was a quack remedy. His spirits felt and, after two months, he relapsed. His physician, certainly realizing the power of placebos, told Wright that a new, stronger formulation of the serum was most promising. He gave the patient a series of injections with plain water, telling him it was "a new super-refined, double-strength" version of the drug. Again the tumors shrank and the symptoms vanished for another two months--until Wright read a newspaper article headlined "Nationwide AMA Tests Show Krebiozen to Be Worthless as a Cancer Treatment." He died two days later.

(*) References to animal testing do not reflect the opinions of this magazine.



By Alex Silberman

Alex Silberman is a freelance health writer in upstate New York.

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