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'Two, Four, Six, Eight... This Pill Works Great!'

Doctors Try Placebo Effect to Boost Power Of Real Drugs; Manipulating the Patient

By AMY DOCKSER MARCUS
Staff Reporter of THE WALL STREET JOURNAL

Medical research has long suggested that some sick people will feel better after taking a dummy pill just because they think it is real medicine. Now doctors are working to harness the mysterious placebo effect to make real drugs work better.

The idea is basically to enhance the benefits of pills through the power of positive thinking. As prescription drugs grow increasingly costly, that effort has important implications. Physicians say that if they can figure out how the placebo effect works and use it to improve drug efficacy, they may be able to reduce dosage for many people, leading to cost savings, fewer side effects, and improved compliance with doctor's orders.

Many doctors say that they often notice that patients seem to respond better and recover more quickly after a positive prognosis. "But for a long time, this idea was treated as akin to practicing voodoo," says Lanny J. Rosenwasser, an asthma specialist at National Jewish Medical and Research Center in Denver. A spate of new clinical trials is now seeking scientific evidence to back up such anecdotal observations. If they find it, the standard visit to the doctor's office could be transformed.

Researchers are experimenting with various messages. One trial seeking to determine if the asthma drug montelukast will work better if presented in an enthusiastic light divides patients into two groups both of whom receive information about the drug from nurse coordinators. One group will hear such statements as: "You can prevent asthma attacks if you use this drug" and "People who use this drug have improved control of their asthma, better health and better quality of life." The other group merely gets written materials about asthma triggers, the importance of adhering to asthma therapy and other related topics.

But trying to enhance a drug's efficacy by manipulating a patient's view of it also raises tricky ethical questions. All medicines have side effects. If a doctor starts enumerating them, the placebo effect may dissipate. Yet failing to make them clear may be unethical. "It's a tough dance," says Bruce Barrett, a doctor with the family medicine department at the University of Wisconsin School of Medicine in Madison.

The interest in the concept is partly the result of tremendous advances in technology that allow scientists to actually study brain responses to active drugs and placebos . Through new imaging equipment, researchers can see what part of the brain lights up when either a drug or a placebo hits. They are now examining whether there is a change in brain activity when a patient expects a drug to be beneficial.

Another driving force is a growing resentment among many doctors that managed care has severely curtailed the amount of time they spend with patients. In a number of the newly launched trials, one of the questions researchers are trying to explore is whether a positive doctor-patient relationship can actually make a drug work better. If so, that could provide ammunition for doctors who want more leeway and reimbursement for spending time with patients.

The growing interest in putting the placebo effect to use in the dispensing of real medication comes as the classic placebo falls on hard times. Debate is growing over the ethics of continuing to use dummy pills as part of drug trials. Many trials contain a placebo arm to help reduce bias when evaluating how much of a patient's positive response to a new drug is from the drug itself rather than participants' expectations that they are going to feel better. But some clinicians have argued that given how many effective treatments are now available, it would be more ethical to test new drugs against currently existing ones rather than against dummy medicine.

Controversial Study

In a controversial and widely challenged study published in 2001 in The New England Journal of Medicine, two Danish researchers analyzed 114 published studies involving over 40 different medical conditions and found little support for the idea that placebos work. They contend that the reason why some patients' conditions improved while taking dummy pills is probably because even in the most intractable disease, people go through periods when they feel better or worse.

Now, new studies are underway that seek to explore the impact of the placebo effect on real drugs. The National Institutes of Health is funding more than a half-dozen studies exploring the issue. The studies are focusing on conditions such as asthma and hypertension, where it is generally accepted that there are psychological components to the intensity of a patient's symptoms. Results may start coming in as early as next year.

Dr. Rosenwasser is working on a three-center study under the auspices of the Mind Brain Body and Health Initiative in Galveston, Texas, to determine whether a common asthma drug, salmeterol, works better when the doctor speaks enthusiastically about it. One doctor will express excitement about the drug and engage patients in discussion about it. Another will be more perfunctory, taking less time talking with patients, and walking out of the room after a minute or two of discussion. Ted Kaptchuk, who heads a placebo working group at Harvard Medical School, is leading a trial involving a drug used to treat an intractable, common gastrointestinal disorder. Some patients will be treated with the drug by a doctor who is warm and positive about the medicine, who sits thoughtfully as the patient explains the symptoms and case history, and leans in to touch the patient from time to time. Others will be treated by a doctor who gives a more matter-of-fact presentation of the medicine's benefits and then leaves the room.

"We have these great, powerful, ever-more-effective medicines," says Mr. Kaptchuk. "But we believe that the loss of the art of medicine makes these medicines less effective than they could be."

Until recently, most research on the placebo effect focused on how patients respond to positive spin in the context of receiving dummy pills. Some of these old studies are now being mined for tantalizing clues into how the effect might enhance the power of real pills.

One study conducted 20 years ago, for example, looked at a group of people with hypertension. Some of the patients in this study got active blood pressure medicine for a week, then no drugs for a week, and dummy pills that looked like the real medicine the third week. The study found that patients' blood pressure went up the week they did not take any drugs, but dropped again as soon as they went back on medicine even though the medicine during the third week was placebo .

Beating Cancer

Larry Streeter, a 47-year-old lymphoma survivor from Natick, Mass., understands first-hand the value of a physician's spin on things. After being diagnosed with cancer, he underwent a rigorous treatment involving radiation and chemotherapy. Throughout his ordeal, his radiologist was upbeat and positive, telling Mr. Streeter every time he saw him that he was going to beat the disease.

Only later, after his chemotherapy was over, did Mr. Streeter ask the doctor just how bad the tumor had been. "We gave you a less than 50-50 chance of surviving," Mr. Streeter says the doctor informed him. When Mr. Streeter asked why the doctor hadn't told him that the odds were against him, the doctor replied, "You didn't ask me so I figured you didn't want to know."

Mr. Streeter has been cancer-free for 18 years now. He believes his doctor's approach made a powerful difference, "My doctor's attitude from the minute I met him gave me the sense of confidence that this could be beat and would be beat."