Placebo Effect

[Michael Scally MD]

The following finding is not surprising. the same can be said for non-placebo therapies that have no support in the scientific literature.


Placebo treatments stronger than doctors thought
http://www.washingtonpost.com/wp-dyn/content/article/2010/02/18/AR2010021804873.html (Placebo treatments stronger than doctors thought - washingtonpost.com)

By MARIA CHENG
The Associated Press
Thursday, February 18, 2010; 7:01 PM

LONDON -- When it comes to the placebo effect, it really may be mind over matter, a new analysis suggests.

In a review of recent research, international experts say there is increasing evidence that fake treatments, or placebos, have an actual biological effect in the body.

The doctor-patient relationship, plus the expectation of recovery, may sometimes be enough to change a patient's brain, body and behavior, experts write. The review of previous research on placebos was published online Friday in Lancet, the British medical journal.

"It's not that placebos or inert substances help," said Linda Blair, a Bath-based psychologist and spokeswoman for the British Psychological Society. Blair was not linked to the research. "It's that people's belief in inert substances help."

While doctors have long recognized that placebos can help patients feel better, they weren't sure if the treatments sparked any physical changes.

In the Lancet review, researchers cite studies where patients with Parkinson's disease were given dummy pills. That led their brains to release dopamine, a feel-good chemical, and also resulted in other changes in brain activity.

"When you think you're going to get a drug that helps, your brain reacts as if it's getting relief," said Walter Brown, a clinical professor of psychiatry at Brown and Tufts University. "But we don't know how that thought that you're going to get better actually translates into something happening in the brain."

With growing proof that placebos work, some doctors are trying to figure out how to capitalize on their effects, without being unethical.

Blair said that to be completely honest with patients - to tell them they were receiving a fake treatment - would sabotage their belief in the drug, and thus, undermine any potential benefit.

But Brown didn't agree. For certain patients, like those with mild depression or anxiety, he said placebos were likely to work just as well as established therapies.

He said that even if doctors acknowledge they are giving such patients a placebo medication, but say it could be beneficial, "it might just actually work."

See: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61706-2/abstract

 

[Michael Scally MD]

The Placebo Effect is very powerful. While this can cloud any treatment, particularly those with no scientific support, another issue is compliance.

Best Ways to Deal With Noncompliant Patients

Mark Crane, BA
Posted: 06/05/2009

Introduction

Once you've figured out what's ailing your patient, the real challenge is convincing him or her to follow your advice. Only half of all chronically ill patients take medicines as directed, and many don't even bother to get the prescription filled, according to a 2003 World Health Organization study.

Beyond that, many patients refuse to make recommended lifestyle changes that can improve their health.

Noncompliance is dangerous for the patient and frustrating for the physician. As more insurers and Centers for Medicare & Medicaid Services (CMS) promote pay-for-performance programs, physicians will potentially be scored and reimbursed on the basis of patient outcomes -- meaning that noncompliant patients could drag down doctors' scores.

Continue Reading (Attachment) . . .

 

[Michael Scally MD]

The Nothing Cure
Matthew Herper and Robert Langreth 03.29.10, 12:00 AM ET
http://www.forbes.com/forbes/2010/0329/opinions-placebo-harvard-health-medicine-ideas-opinions_print.html


Though recurring tummy aches from irritable bowel syndrome are among patients' most common complaints, drugmakers have had trouble coming up with a safe and effective treatment. But in 2008 Harvard's Ted J. Kaptchuk devised a safe remedy that helps far more people than any designer drug ever did.

His magic cure: fake acupuncture delivered with lots of warm talk from a sympathetic acupuncturist--but no needles. In a trial of 262 patients with severe IBS, 62% of those who received the fake treatment got better, according to results published in the British Medical Journal. By comparison, only 28% of a control group of patients put on a waiting list saw their symptoms improve markedly. A third group who got the fake acupuncture, but without any warm talk, showed in-between results: 44% improved.

The result, says Kaptchuk, shows just how much the expectation of a cure--and the rituals associated with medical treatment--can improve real-world symptoms. "Our own will, imagination and belief can modulate the course of illness," says Kaptchuk.

Kaptchuk is among a small band of researchers studying the mechanisms behind the mysterious placebo effect. They are finding that the mere expectation that a treatment will help produces lasting effects on symptoms of many diseases--and real changes inside patients' brains. Certainly placebos will never cure cancer or heart disease. But believing in a treatment may ease back pain, improve Parkinson's disease symptoms, alleviate depression and lessen nausea.

Mainstream medicine has tended to dismiss or ignore the placebo effect. Drug companies try to minimize it when conducting clinical trials. But Kaptchuk argues that doctors should instead do everything in their power to try enhance it by hyping up the rituals around their treatments. Doing so could help make existing treatments more effective and may reduce the need for expensive pills that have lots of side effects. "The ritual of health care has an important role to play that gets overlooked," says Kaptchuk.

Kaptchuk's research helps explain why doctors often think they have found a breakthrough treatment, only to find to their embarrassment years later that a placebo pill or other sham treatment works just as well. Knee arthroscopy was long thought to be a good treatment for arthritis pain. In 2002 a rigorous clinical trial found that patients got just as much relief from a fake surgery. Last summer two major trials tested vertebroplasty, a procedure to relieve pain from osteoporosis fractures by injecting cement into the back. Doctors had reported a high success rate. But it turned out that a fake surgery with no cement was just as good. It was all in the expectation.

The most recent big brouhaha is over studies in the Journal of the American Medical Association and PLoS Medicine finding that antidepressants barely beat sugar pills for mild and moderate depression. "The question is: Are we all fooling ourselves, telling ourselves that the improvement is caused by a pill when it's actually caused by the nice interaction we've had with our patients?" wonders psychiatrist and blogger Daniel Carlat. "A big part of what gets people better when they take pills is something other than the neurochemical action." Carlat thinks the pills work.

Kaptchuk, 62, has a college degree in religious studies from Columbia University and is one of the few Harvard medical professors without a Western graduate degree. An expert in acupuncture, he became interested in the placebo effect while getting a doctorate in Chinese medicine at the Macau Institute of Chinese Medicine in China in the 1970s (Massachusetts law doesn't allow him to call himself a doctor). He now leads a dozen investigators studying the placebo effect, funded with grants from the National Institutes of Health.

A placebo, he says, is the sum total of all the psychological benefits patients get from seeing their doctors and taking their pills. One theme of his research is that the bigger and more complicated the ritual, the greater the placebo effect. Surgery and medical devices often produce a bigger placebo effect than a pill because expectations for a cure are higher, he says. In a British Medical Journal article in 2006, for example, Kaptchuk and his colleagues reported treating 270 people suffering severe arm pain from repetitive-use injuries with either a placebo pill or fake acupuncture. The people who got the fake acupuncture reported significantly greater reductions in self-reported pain, even though there was no difference in posttreatment grip strength between the groups.

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Certainly doctors and patients routinely underestimate how often symptoms will get better on their own. Back pain, irritable bowel syndrome, depression and anxiety tend to wax and wane over time. People report to the doctor's office when symptoms are worst. They assume the treatment they get is responsible for any improvement, even though they might have got better anyway. Some say this is not a true placebo effect.

But recent brain-imaging studies show that fake treatments can produce real effects deep inside the brain. One of the scientists performing these studies is University of Colorado psychologist Tor Wager, 35. Over the years "there has been tons of skepticism" that the placebo effect really exists, says Wager. He was skeptical himself when he first started doing brain scans of patients on placebos as a grad student at the University of Michigan. But now, he says, "the science has really exploded."

In recent years researchers have proved that the placebos alter the perception of pain inside the brain. The expectation of getting treated turns on the brain's reward system, causing the brain to produce dopamine and natural narcoticlike chemicals. This can trigger pain relief even in the absence of a drug. "The placebo effect is a real thing, and it is tied to an old, hardwired pain-control pathway," says Falk Eippert, a researcher at University Medical Center Hamburg-Eppendorf in Germany. "It is not some kind of elusive phenomenon."

In 2004 Wager and his colleagues applied an inert cream to the arms of 50 volunteers, then pressed a painfully hot ceramic plate against their arms while the subjects were inside a magnetic resonance imaging machine. Half the time the researchers lied to the subjects. "We told them it was a powerful pain-relieving drug," Wager says. The rest of the time they admitted the cream was inert. When volunteers thought they were getting a real drug, they reported 20% less pain. Neuronal activity in regions of the brain that encode pain intensity subsided, the MRI showed.

The next year neuroscientist Jon-Kar Zubieta of the University of Michigan used a different type of brain scan (positron emission tomography) to delve more deeply into what goes on at the molecular level when people receive a placebo. He showed that when patients think they are getting a painkiller--but are getting a placebo--it stimulates some of the same molecular receptors in the brain that the narcotic painkiller morphine hits.

Another ailment where there is mounting evidence for a placebo effect is Parkinson's disease. In this disease dopamine-producing cells in the brain gradually die. A 2001 University of British Columbia study in the journal Science gave six Parkinson's disease patients a placebo and then examined their brains with positron emission tomography. The expectation of relief triggered large amounts of dopamine to be released inside the damaged areas of the brain.

Placebo is Latin for "I shall please," and for two centuries the word has been used to refer to inactive treatments given to make patients happy. The concept of a placebo effect was popularized in a 1955 JAMA article by anesthesiologist Henry Beecher, "The Powerful Placebo." It made a case for performing placebo-controlled trials of new drugs.

Some are still skeptics. Danish epidemiologist Asbjørn Hróbjartsson calls the placebo effect "grossly exaggerated." Hróbjartsson analyzed 202 studies comparing placebo treatments for various diseases with no treatment and found only a clear statistically significant placebo effect for two conditions: pain and nausea. He says a lot of what gets called the placebo effect is really patients getting better on their own or exaggerating symptom improvements to please their doctors.

While drug companies are desperate to get rid of the placebo effect, the opposite is true in clinical practice. A 2008 survey of U.S. internists and rheumatologists found that half of them prescribed placebos, including sugar pills, vitamins and supplements they did not expect to have an effect on anything aside from the patient's own belief. But it may be possible to enhance the placebo effect even when active drugs are being used. "We do a lot to undermine the placebo effect" by making pill-taking mechanical, argues Duke University behavioral economist Dan Ariely. In a 2008 experiment he found that more people get pain relief from a placebo that supposedly costs $2.50 a pill than from a placebo they think costs only 10 cents per pill.

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To enhance patients' expectations, drugs could come in colorful packaging instead of plain white bottles, says Ariely, author of Predictably Irrational. The term "generic drug" should be abandoned because it is associated with cheapness, he says. Ariely became aware of the placebo effect after suffering severe burns in an explosion. At the hospital he was at in Israel, morphine doses were limited to prevent addiction. Sometimes patients exhausted their daily rations and would be crying in agony. "The nurses would give them a placebo injection, and they would go to sleep. It was unbelievable," he says.

Another possibility: It may able be possible to take advantage of the placebo effect to lower the amount of drug needed to treat a patient. This could save money and prevent side effects. Only a handful of small studies have explored this concept. In one trial of 46 psoriasis patients, psychologist Robert Ader from the University of Rochester School of Medicine & Dentistry found it was possible to reduce the amount of steroids needed to treat psoriasis by half, giving patients the full dose of steroids some days and a placebo cream on others. "The brain interacts with the immune system in all sorts of ways--there are communications in both directions," Ader says.

It could take decades for researchers like Kaptchuk and Wager to parse all the psychological and neurobiological mechanisms behind the placebo effect. They may never come up with a clear answer as to what is going on. Meanwhile, the next time your doctor recommends an expensive drug or complicated operation to relieve everyday symptoms, it may pay to ask him a simple question. Will the treatment beat a placebo?

 

[Andrew Androgen]

What would happen in the reverse situation where a person strongly believed that what they were taking would have no effect at all? Would the drug have less effect on these people?

 

[Michael Scally MD]

Doctor May Be Most Reliable Source Of Strong Placebo Effect.

The New York Times (5/3, Judson) "Opinionator" blog discussed the placebo effect, which could be considered "one of the most powerful forces in medicine." Interestingly, "the most reliable source of a strong placebo effect appears to be: the doctor." Some studies suggest that "placebo treatments are more powerful if your doctor believes in them. They are also more powerful if the doctor tells you so." But, "since deception of patients is unethical, some argue that the placebo has no place in the actual practice of medicine." Others, including the blog author, believe it is time for modern medicine to learn how to enhance the power of the placebo to help patients.


Enhancing the Placebo
Enhancing the Placebo - Opinionator Blog - NYTimes.com

By OLIVIA JUDSON


The placebo effect is, potentially, one of the most powerful forces in medicine. The challenge is to harness that power in a reliable and systematic way.

First, what is the placebo effect?

It’s the improvement in health that some patients experience because of the feeling that they are receiving medical care. A classic example comes from drug trials. Suppose patients are randomly divided into three groups: those who get no treatment, those who get the drug that’s being tested, and those who get the placebo treatment — typically a pill that looks and tastes like the drug, but doesn’t contain it, or any other active ingredient.

The idea is that the “no treatment” group shows how many people would have gotten better by themselves; the “placebo” group shows any effect of participating in medical rituals (like taking pills); the “drug” group shows any effect of the drug over and above the effect of medical rituals. Simple.

Or not. Different studies of the placebo effect report wildly different results. One survey of 117 trials of two ulcer drugs found that, depending on the trial, patients in the placebo group had anywhere from zero to a 100 percent recovery rate.

The drugs also varied in their effectiveness from one trial to the next; sometimes patients on the placebo did better than those on the drug. Intriguingly, the results varied from country to country, with Brazilians showing no placebo effect and Germans having a strong one. Why? No one knows, but it doesn’t appear to be because of anything inherently German: trials of drugs for hypertension found a weaker placebo effect in Germany than in other countries.

The problem is that humans are not machines, and emotions are not abstractions. Hope and expectation, anxiety and fear, trust and suspicion — these cause physiological changes in the brain that can interact with drugs, changing their effects.

This is even true for a drug like morphine. Yes, it’s a powerful painkiller. But it’s far more powerful if a doctor marches in, tells you he’s going to give you morphine, and injects you, than it is if it is administered secretly by a hidden machine.

Differences in hopes and fears, and the resulting physiological changes, may explain why the placebo effect varies so much: individual experiences matter. Some people are more anxious than others, or may find the thought of a particular disease especially alarming. Moreover, in different cultures, similar diseases may be treated with different degrees of gravity.

Expectations around medical rituals may also explain why placebos tend to be more powerful if the pills are expensive or you take them several times a day; why injections and exotic machines are more powerful than pills; and why surgery is more powerful than injections. (In placebo surgery, the patient is anaesthetized, cut, and sewn back up again, but no manipulation is done. For obvious reasons, there have been few tests of this. But when it has been done, it has often produced good results for the patients.)

However, the most reliable source of a strong placebo effect appears to be: the doctor.

Placebo treatments are more powerful if your doctor believes in them. They are also more powerful if the doctor tells you so. In one study, for example, patients who had just come out of surgery were given a saline infusion, and — whenever they asked for it — the pain killer buprenorphine. However, some patients were told the saline infusion was a powerful painkiller, others that it might be one, while a third group wasn’t told anything. Over the course of three days, those in the “know-nothing” group asked for more buprenorphine than those in the “maybe” group, who in turn asked for more than those told they were getting a real drug.

Which highlights a problem. Since deception of patients is unethical, some argue that the placebo has no place in the actual practice of medicine.

But the matter is more nuanced. As the morphine example shows, the placebo effect also enhances “real” treatments. So the key is to figure out how to maximize that enhancement without lying. One idea would be to deliberately increase the element of formal ritual in medicine. Studies of “alternative” therapies show that strong placebo effects can be induced by ritual. Indeed, in mainstream medicine, surgery is the treatment most surrounded by ritual; perhaps this is one reason it appears to be the most powerful placebo.

To be sure, many questions still need to be answered. But one thing is clear. It’s time we stopped treating the placebo effect as a nuisance — something that rational humans shouldn’t have. Instead, we must learn to purposefully enhance its power.


Notes:

The placebo effect has generated a vast and complex literature; my treatment of the topic is necessarily brief.

For anyone interested in a fascinating overview of the complexities of the placebo effect, see Moerman, D. 2002. “Meaning, Medicine, and the ‘Placebo Effect.’ ” Cambridge University Press. I particularly recommend chapters 4 and 5; the first is on the importance of doctors, the second is on how different placebo regimes (pills, shots, surgery) compare with each other, and also how different regimens (taking pills four times a day as against once a day) can change the effectiveness of the placebo.

Anyone interested in the history of the placebo effect should read Shapiro, A. K. and Shapiro, E. 1997. “The Powerful Placebo: From Ancient Priest to Modern Physician.” Johns Hopkins University Press. Note that the understanding of the physiology of the placebo effect has advanced considerably since this book was published.

A number of authors have written thoughtfully about enhancing the placebo effect. See, for example, Greene, C. S. et al. 2009. “Placebo responses and therapeutic responses. How are they related?” Journal of Orofacial Pain 23: 93-107; Finnis, D. G. et al. 2010. “Biological, clinical, and ethical advances of placebo effects.” The Lancet 375: 686-695; and Miller, F. G., Colloca, L. and Kaptchuk, T. J. 2009. “The placebo effect: illness and interpersonal healing.” Perspectives in Biology and Medicine 52: 518-539. See also Pacheco-López, G., et al. 2006. “Expectations and associations that heal: immunomodulatory placebo effects and its neurobiology.” Brain, Behavior, and Immunity 20: 430-446.

For the 117 studies of ulcer drugs, see Moerman, D. E. 2000. “Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure.” Medical Anthropology Quarterly 14: 51-72. For physiological changes to the brain in response to the anticipation of receiving pain killers, see Colloca, L. and Benedetti, F. 2005. “Placebos and painkillers: is mind as real as matter?” Nature Reviews Neuroscience 6: 545-552; and Price, D. D., Finniss, D. G. and Benedetti, F. 2008. “A comprehensive review of the placebo effect: recent advances and current thought.” Annual Reviews of Psychology 59: 565-590. This paper also discusses ways in which conditioning and memory may contribute to placebo responses. A number of papers have considered hidden versus open injections of drugs; for morphine in particular, see for example, figure 2 of Colloca, L. et al. 2004. “Open versus covert treatment for pain, anxiety, and Parkinson’s disease.” The Lancet Neurology 3: 679-684.

For expensive placebo pills being more effective than cheap ones, see Waber, R. L. et al. 2008. “Commercial features of placebo and therapeutic efficiency.” Journal of the American Medical Association 299: 1016-1017. For sham devices being more powerful than placebo pills, see Kaptchuk, T. J. et al. 2006. “Sham device versus inert pill: randomised control trial of two placebo treatments.” British Medical Journal 332: 391-394.

Sham surgery is controversial. For discussions of it, see Macklin, R. 1999. “The ethical problems with sham surgery in clinical research.” New England Journal of Medicine 341: 992-996; and Johnson, A. G. 1994. “Surgery as a placebo.” The Lancet 344: 1140-1142. For evidence of its power, see McRae, C. et al. 2004. “Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial.” Archives of General Psychiatry 61: 412-420; and Goetz, C. G. et al. 2008. “Placebo response in Parkinson’s disease: comparisons among 11 trials covering medical and surgical interventions.” Movement Disorders 23: 690-699.

Doctors’ belief in the treatment can manifest itself in a variety of ways: if a doctor thinks the patient may have received a powerful painkiller, patients report less pain than if the doctor knows they have not. Similarly, a doctor’s enthusiasm for a procedure often enhances its effect — for further information on this, see the Moerman book mentioned above. For the experiment involving the infusion of saline solution masquerading as a powerful drug, see Pollo, A. et al. 2001. “Response expectancies in placebo analgesia and their clinical relevance.” Pain 93: 77-84.

In general, prescribing placebo treatments is considered to be bad medicine (see a recent report by Britain’s Parliament - UK Parliament - S&T Homeopathy inquiry .) For an alternative view, see Foddy, B. 2009. “A duty to deceive: placebos in clinical practice.” American Journal of Bioethics 9: 4-12. For ways in which the placebo effect may be harnessed by “alternative” medical practices, see Kaptchuk, T. J. 2002. “The placebo effect in alternative medicine: can the performance of a healing ritual have clinical significance.” Annals of Internal Medicine 136: 817-825.

Many thanks to everyone who has listened to my musings on the placebo effect, and to Mike Eisen for pointing out the study of Brazilians versus Germans. But particular thanks are due to Sofia Castello y Tickell, Dan Haydon, and Jonathan Swire for insights, comments and suggestions.