Wise Young
04-30-2002, 02:26 AM
http://www.siliconvalley.com/mld/siliconvalley/news/local/3163892.htm
New study of brain illustrates power of placebos
By Barbara Feder Ostrov
Mercury News
Fifty years ago, physician supply catalogs carried a wide array of sugar pills and tonics in all kinds of shapes and colors. Known as placebos, these were sham medicines, inert substances that sometimes made sick patients feel better, especially when they came from a kindly, authoritative family doctor.
Physicians no longer dispense sugar pills, of course. But the placebo effect remains a powerful force in modern medicine, a mysterious victory of mind over body that seems to flout the cherished objectivity of medical science.
New brain-imaging studies show for the first time how and where the placebo effect kindles changes in the brain, renewing interest in the topic. Researchers are searching for ways healers can work with the placebo effect, rather than against it, to help patients -- an endeavor in keeping with Americans' keen interest in alternative medicine.
The goal, says Dr. David Spiegel, a Stanford University psychiatrist, is to study placebos in the context of ``how we can use them, rather than view them as a nuisance factor.''
Study after study has shown that although their effects are often temporary, placebos can lower heart rate, relieve pain, reduce kidney stones, alleviate asthma and lift depression -- yet their effects are often temporary.
Scientists theorize that placebos can activate the same neural pathways as potent medicines, through a complex psychological calculus of people's expectations, behavioral conditioning and the meanings they attach to medicine and its rituals.
In one University of California-Los Angeles study, for example, researchers found that depressed patients who received a placebo showed activity in the same brain regions as patients who received a true anti-depression medication.
Brain-imaging studies such as these have generated intense interest, even excitement, among scientists because they provide direct clinical evidence of an effect that is still regarded with deep ambivalence by the medical community.
Long history of use
In Latin, the word placebo means ``I will please.''
``For many centuries, medicine had little to offer but the placebo effect,'' says Dr. Harry Guess of Merck Research Labs, who co-chaired a National Institutes of Health conference on placebos in 2000.
Throughout medical history, doctors have prescribed all manner of outlandish medicines to their patients, among them theriac, or viper's flesh, crocodile dung, Egyptian willow leaves and burnt sea sponges. Later, patent medicines emerged with creative names like ``Kickapoo Indian Pills,'' hawked as cures for a wide variety of illnesses.
With the rise of effective modern medicines, however, placebos began to assume a negative image, as a medicine designed more to placate than benefit the patient, Guess said.
In a defining study on the placebo effect published in 1955, Dr. Henry Beecher found that roughly one-third of patients responded to dummy treatment. Seeing its power, he urged researchers to adopt then-emerging, but now standard, clinical trial methodologies that carefully watch for the placebo effect -- otherwise, how would researchers know whether it was their drug or therapy alone that helped patients?
Since then, the placebo effect has been seen in hundreds of clinical studies, including trials of new ulcer and asthma drugs as well as treatments for depression. The placebo effect has also been noted in surgery trials.
Sham surgery
In one famous 1950s-era study, researchers showed that sham surgery, in which patients' chests were opened but no procedures were performed, was actually more effective than a surgical treatment for angina. The treatment is no longer used.
More recently, scientists have found that patients with osteoarthritis of the knee benefited from simple incisions made in the knee, faring about as well as patients who received traditional arthroscopic surgery.
In one controversial study, however, Copenhagen researchers analyzed 114 published studies involving more than 7,000 patients with 40 different conditions and concluded that the placebo effect was a myth. They found that patients given no treatment at all improved at the same rate as patients given placebos, except in the area of pain relief, where they did note a placebo effect.
That study has since been roundly criticized, with scientists saying the researchers compared studies that were too dissimilar and included too many different medical conditions.
``What they thought they proved is that that the placebo effect doesn't do anything,'' Spiegel said. ``What they proved is that it doesn't do everything.''
Scientists now know that the placebo effect seems to be more common in diseases where there might be intermittent remissions or cycles of symptoms, such as arthritis, said Dr. Terrence Blaschke, a Stanford University professor of medicine.
Placebos don't seem to work in curing infection or wounds. But they appear quite effective in alleviating depression, as well as pain: In one study, a sham injection of saline solution was enough to relieve the pain of wisdom teeth extraction in 30 to 40 percent of patients.
Researchers long have tried to discern what makes a person ``placebo-responsive,'' at various points positing that women, the illiterate, and the poor might be more prone to the power of suggestion. But researchers haven't found any socioeconomic factors that explain who might respond more strongly to placebos, Blaschke said.
Ritual may provide relief
Scientists have theorized that placebos gain some of their power through conditioning and expectations. Certain rituals, such as going to the doctor or taking a pill, are associated with relief of some symptoms, and may provide relief by themselves.
One study by Italian researchers found that when patients did not know they were receiving a medicine, it did not work as well as when the patients knew they were getting it.
But the physiological underpinnings of the placebo effect have remained unclear.
Researchers believe that placebos may work by triggering the same brain signals that activate the release of natural painkillers known as endogenous opiates. These opium-like substances tend to be produced in greater quantities when the body anticipates relief from pain.
In one recent study published in the journal Science, Swedish researchers used brain imaging to compare responses of subjects who had been given either injections of an opioid painkiller or a placebo, then had a hot metal plate pressed to the backs of their hands. The positron emission tomography, or PET, scans used by the researchers showed that both the painkiller and the placebo increased blood flow in an area of the brain, known as rostral ACC, that is rich in opioid receptors. Other studies have shown that a drug, naloxone, that counteracts the effects of endogenous opiates can block the placebo effect.
Still, scientists are careful to note that distinguishing the placebo effect in studies where brain imaging is not conducted can be difficult: Patients may heal spontaneously on their own, or their symptoms may return to average after an acute flare-up, and that will look like improvement.
Doctors slow to apply research
For all that scientists have learned about the placebo effect, their conclusions have largely remained in the lab.
``This knowledge is very slow in getting to the physician's office,'' said placebo expert Dr. Howard Brody of Michigan State University. ``More research is needed to firm up this knowledge, but the things the physician can do are so low-risk and cheap that it makes no sense not to do them just because the final research answer is not in.''
Now that the National Institutes of Health is funding more placebo research, Brody and others have proposed studies that look at how a doctor's demeanor and attitude can help stimulate a placebo effect that can strengthen conventional medical treatment. In one study that Brody is preparing, he and his colleagues will study patients who are being seen in a doctor's office for pain symptoms, and how the doctor's approach affects how the patient feels two weeks later.
Brody advises physicians to listen carefully to patients, explain their symptoms or illness, show concern and compassion, and show them ways to take control of their disease.
``What research is now available shows that each one of these probably can produce a positive placebo effect in the setting of a usual office visit,'' Brody said.
------------------------------------------------------------------------
Contact Barbara Feder Ostrov at bfeder@sjmercury.com or (408) 920-5064.
New study of brain illustrates power of placebos
By Barbara Feder Ostrov
Mercury News
Fifty years ago, physician supply catalogs carried a wide array of sugar pills and tonics in all kinds of shapes and colors. Known as placebos, these were sham medicines, inert substances that sometimes made sick patients feel better, especially when they came from a kindly, authoritative family doctor.
Physicians no longer dispense sugar pills, of course. But the placebo effect remains a powerful force in modern medicine, a mysterious victory of mind over body that seems to flout the cherished objectivity of medical science.
New brain-imaging studies show for the first time how and where the placebo effect kindles changes in the brain, renewing interest in the topic. Researchers are searching for ways healers can work with the placebo effect, rather than against it, to help patients -- an endeavor in keeping with Americans' keen interest in alternative medicine.
The goal, says Dr. David Spiegel, a Stanford University psychiatrist, is to study placebos in the context of ``how we can use them, rather than view them as a nuisance factor.''
Study after study has shown that although their effects are often temporary, placebos can lower heart rate, relieve pain, reduce kidney stones, alleviate asthma and lift depression -- yet their effects are often temporary.
Scientists theorize that placebos can activate the same neural pathways as potent medicines, through a complex psychological calculus of people's expectations, behavioral conditioning and the meanings they attach to medicine and its rituals.
In one University of California-Los Angeles study, for example, researchers found that depressed patients who received a placebo showed activity in the same brain regions as patients who received a true anti-depression medication.
Brain-imaging studies such as these have generated intense interest, even excitement, among scientists because they provide direct clinical evidence of an effect that is still regarded with deep ambivalence by the medical community.
Long history of use
In Latin, the word placebo means ``I will please.''
``For many centuries, medicine had little to offer but the placebo effect,'' says Dr. Harry Guess of Merck Research Labs, who co-chaired a National Institutes of Health conference on placebos in 2000.
Throughout medical history, doctors have prescribed all manner of outlandish medicines to their patients, among them theriac, or viper's flesh, crocodile dung, Egyptian willow leaves and burnt sea sponges. Later, patent medicines emerged with creative names like ``Kickapoo Indian Pills,'' hawked as cures for a wide variety of illnesses.
With the rise of effective modern medicines, however, placebos began to assume a negative image, as a medicine designed more to placate than benefit the patient, Guess said.
In a defining study on the placebo effect published in 1955, Dr. Henry Beecher found that roughly one-third of patients responded to dummy treatment. Seeing its power, he urged researchers to adopt then-emerging, but now standard, clinical trial methodologies that carefully watch for the placebo effect -- otherwise, how would researchers know whether it was their drug or therapy alone that helped patients?
Since then, the placebo effect has been seen in hundreds of clinical studies, including trials of new ulcer and asthma drugs as well as treatments for depression. The placebo effect has also been noted in surgery trials.
Sham surgery
In one famous 1950s-era study, researchers showed that sham surgery, in which patients' chests were opened but no procedures were performed, was actually more effective than a surgical treatment for angina. The treatment is no longer used.
More recently, scientists have found that patients with osteoarthritis of the knee benefited from simple incisions made in the knee, faring about as well as patients who received traditional arthroscopic surgery.
In one controversial study, however, Copenhagen researchers analyzed 114 published studies involving more than 7,000 patients with 40 different conditions and concluded that the placebo effect was a myth. They found that patients given no treatment at all improved at the same rate as patients given placebos, except in the area of pain relief, where they did note a placebo effect.
That study has since been roundly criticized, with scientists saying the researchers compared studies that were too dissimilar and included too many different medical conditions.
``What they thought they proved is that that the placebo effect doesn't do anything,'' Spiegel said. ``What they proved is that it doesn't do everything.''
Scientists now know that the placebo effect seems to be more common in diseases where there might be intermittent remissions or cycles of symptoms, such as arthritis, said Dr. Terrence Blaschke, a Stanford University professor of medicine.
Placebos don't seem to work in curing infection or wounds. But they appear quite effective in alleviating depression, as well as pain: In one study, a sham injection of saline solution was enough to relieve the pain of wisdom teeth extraction in 30 to 40 percent of patients.
Researchers long have tried to discern what makes a person ``placebo-responsive,'' at various points positing that women, the illiterate, and the poor might be more prone to the power of suggestion. But researchers haven't found any socioeconomic factors that explain who might respond more strongly to placebos, Blaschke said.
Ritual may provide relief
Scientists have theorized that placebos gain some of their power through conditioning and expectations. Certain rituals, such as going to the doctor or taking a pill, are associated with relief of some symptoms, and may provide relief by themselves.
One study by Italian researchers found that when patients did not know they were receiving a medicine, it did not work as well as when the patients knew they were getting it.
But the physiological underpinnings of the placebo effect have remained unclear.
Researchers believe that placebos may work by triggering the same brain signals that activate the release of natural painkillers known as endogenous opiates. These opium-like substances tend to be produced in greater quantities when the body anticipates relief from pain.
In one recent study published in the journal Science, Swedish researchers used brain imaging to compare responses of subjects who had been given either injections of an opioid painkiller or a placebo, then had a hot metal plate pressed to the backs of their hands. The positron emission tomography, or PET, scans used by the researchers showed that both the painkiller and the placebo increased blood flow in an area of the brain, known as rostral ACC, that is rich in opioid receptors. Other studies have shown that a drug, naloxone, that counteracts the effects of endogenous opiates can block the placebo effect.
Still, scientists are careful to note that distinguishing the placebo effect in studies where brain imaging is not conducted can be difficult: Patients may heal spontaneously on their own, or their symptoms may return to average after an acute flare-up, and that will look like improvement.
Doctors slow to apply research
For all that scientists have learned about the placebo effect, their conclusions have largely remained in the lab.
``This knowledge is very slow in getting to the physician's office,'' said placebo expert Dr. Howard Brody of Michigan State University. ``More research is needed to firm up this knowledge, but the things the physician can do are so low-risk and cheap that it makes no sense not to do them just because the final research answer is not in.''
Now that the National Institutes of Health is funding more placebo research, Brody and others have proposed studies that look at how a doctor's demeanor and attitude can help stimulate a placebo effect that can strengthen conventional medical treatment. In one study that Brody is preparing, he and his colleagues will study patients who are being seen in a doctor's office for pain symptoms, and how the doctor's approach affects how the patient feels two weeks later.
Brody advises physicians to listen carefully to patients, explain their symptoms or illness, show concern and compassion, and show them ways to take control of their disease.
``What research is now available shows that each one of these probably can produce a positive placebo effect in the setting of a usual office visit,'' Brody said.
------------------------------------------------------------------------
Contact Barbara Feder Ostrov at bfeder@sjmercury.com or (408) 920-5064.