The Healing Power Of PLACEBOS

by Tamar Nordenberg

One patient stands out in the memory of Stephen Straus, M.D., for her remarkable recovery, more than 10 years ago, from chronic fatigue syndrome. The woman, then in her 30s, was "very significantly impaired," says Straus, chief of the Laboratory of Clinical Investigation at the National Institute of Allergy and Infectious Diseases. "She had no energy, couldn't work, and spent most of her time at home." But her strength was restored during a study to test the effectiveness of an experimental chronic fatigue drug.

"She and her parents were so thrilled with her recovery that they were blessing me and my colleagues," recalls Straus, the principal investigator on that study.

Like many drug studies, the chronic fatigue medication trial was a "placebo-controlled" study, meaning that a portion of the patients took the experimental drug, while others took look-alike pills with no active ingredient, with neither researchers nor patients knowing which patients were getting which.

It's human nature, Straus explains, for patients and investigators alike to try and guess in each case: Is it the real drug or a dummy pill? But people shouldn't kid themselves, he says, that they can consistently tell the actual drug from the sham by seeking out tell-tale signs of improvement.

Turns out, the woman's quick turnaround from chronic fatigue occurred after taking placebo pills, not the experimental drug. Straus says, "She was amazed by the revelation that she'd gotten better on placebo."

Research has confirmed that a fake treatment, made from an inactive substance like sugar, distilled water, or saline solution, can have a "placebo effect"--that is, the sham medication can sometimes improve a patient's condition simply because the person has the expectation that it will be helpful. For a given medical condition, it's not unusual for one-third of patients to feel better in response to treatment with placebo.

"Expectation is a powerful thing," says Robert DeLap, M.D., head of one of the Food and Drug Administration's Offices of Drug Evaluation. "The more you believe you're going to benefit from a treatment, the more likely it is that you will experience a benefit."

To separate out this power of positive thinking and some other variables from a drug's true medical benefits, companies seeking FDA approval of a new treatment often use placebo-controlled drug studies. If patients on the new drug fare significantly better than those taking placebo, the study helps support the conclusion that the medicine is effective.

Benefiting from Belief

Researchers have been studying the placebo effect for decades. In 1955, researcher H.K. Beecher published his groundbreaking paper "The Powerful Placebo," in which he concluded that, across the 26 studies he analyzed, an average of 32 percent of patients responded to placebo. In the 1960s, breakthrough studies showed the potential physiological effects of dummy pills--they tended to speed up pulse rate, increase blood pressure, and improve reaction Speeds, for example, when participants were told they had taken a stimulant, and had the opposite physiological effects when participants were told they had taken a sleep-producing drug.

Yet, even after 40 years, big questions remain about the interplay of psychological and physiological mechanisms that contribute to the placebo effect. Today's brain imagery techniques do lend support, though, to the theory that thoughts and beliefs not only affect one's psychological state, but also cause the body to undergo actual biological changes.

The phenomenon needn't baffle us, says Michael Jospe, a professor at the California School of Professional Psychology who has studied the placebo effect for more than 20 years. He points out that all people experience physiological reactions to anticipation and stress--something like the fight-or-flight response--that help them to survive and cope. When you step out of your office and a spider jumps out at you, Jospe analogizes, "you'll get a fright and have a physiological reaction. And the next time you go out that way, the thought that it could happen again can produce a physiological reaction before you even open the door." So, he says, the relationship between a thought and a negative psychophysiological reaction like fear is something we experience daily.

That goes for positive associations, too, Jospe continues. "The placebo effect is part of the human potential to react positively to a healer. You can reduce a patient's distress by doing something which might not be medically effective." It's like kids and Band-Aids, Jospe says. "When you put a Band-Aid on a child and it has stars or comics on it, it can actually make the kid feel better by its soothing effect, though there's no medical reason it should make the child feel better."

There is no medical reason, either, that look-alike placebo tablets used in a 1997 study of benign enlargement of the prostate gland should have made the study participants feel better. But in this Canadian study, more than half of the men who got the placebo pills reported significant relief from their symptoms, including faster urine flow. Researcher J. Curtis Nickel theorized that the patients' positive expectations of the experimental drug's benefits may have caused therapeutic smooth muscle relaxation by decreasing nerve activity affecting the bladder, prostate and urethra. Study participants on placebo complained of side effects, too (sometimes called the "nocebo" effect), ranging from impotence and reduced sex drive to nausea, diarrhea and constipation.

It's this powerful placebo effect, coupled with the fact that many medical conditions involve a natural course of better and worse periods (arthritis and multiple sclerosis are examples of diseases with flair-ups and lulls), that can make it difficult to know if a health upswing should be credited to a drug effect. One way to account for such variables in a drug study: give one group of patients placebo and another the experimental drug, and see if the drug group's health improvements sufficiently surpass those from placebo. In Straus' study, the chronic fatigue syndrome drug failed to adequately demonstrate its superiority over dummy pills.

Proof in the Placebo

FDA doesn't require that a drug study include a placebo control group, DeLap says, only that its design be capable of establishing a drug's safety and effectiveness. Non-placebo types of drug studies include "head-to-head" studies, which compare the experimental drug to an existing treatment, and historically controlled studies, which compare the new drug's effects with information gathered in the past about the expected progression of a medical condition.

Often, however, a placebo control can provide the clearest insight into what a treatment can accomplish, according to DeLap, especially with some psychiatric and other drugs in which the placebo effect is known to play a particularly weighty role. In fact, DeLap says, in some cases the placebo effect "makes it almost hopeless, statistically" to use studies that test a new treatment side-by-side against an existing one and determine whether the new treatment works.

The placebo controls that have traditionally been used to test medications have recently been used, too, to test the effectiveness of surgical procedures. In one well-publicized study sponsored by the National Institutes of Health, half of the Parkinson's disease patients enrolled in the trial underwent a sham,surgery in which doctors drilled holes into their skulls but didn't implant the potentially beneficial human fetal tissue in their brains.

While FDA doesn't evaluate the safety or effectiveness of most surgical techniques, the agency does regulate surgical implantation of animal cells or re-engineered human tissues. The agency has approved at least one sham surgery-controlled trial, which will study the effectiveness of implanted pig fetal cells for Parkinson's.

Even with the powerful scientific advantages of including a placebo control, researchers and FDA must look at each treatment individually to decide if the use of placebos is appropriate and ethical. In fact, much medical research does not involve a placebo control because "it's just not an option, ethically," DeLap says.