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Why "placebo" is not a dirty word
Several of my friends swear that a daily dose of glucosamine sulfate -- a dietary supplement prepared from the shells of crabs and other shellfish -- reduces their arthritis-related knee pain and improves their overall mobility.

Yet despite annual U.S. sales of $200 million and decades of medical trials, it remains unclear if glucosamine offers any significant benefit other than that derived from the placebo effect, commonly defined as an inert medication or treatment that can have a therapeutic effect if a patient believes he or she is receiving a beneficial treatment.

The popular glucosamine is only a tip of the complementary and alternative medicine (CAM) iceberg. Health-conscious consumers now spend more than $30 billion a year on CAM therapies. But as a growing body of medical research and the convincing recent book, "Snake-Oil Science: The Truth About Complementary and Alternative Medicine," by R. Barker Bausell, former research director of the National Institutes of Health-funded National Center for Complementary and Alternative Medicine, point out, the primary benefit of CAM therapies is a result of placebo.

Before jumping to the conclusion that I'm on the anti-CAM bandwagon, be assured that the placebo effect is equally prominent in conventional medical therapy. Consider the previously well-accepted surgical procedure for incapacitating wear-and-tear osteoarthritis of the knee -- removal of the bony spurs and degenerated cartilage.

In a landmark 2002 study of 180 patients with demonstrable knee osteoarthritis, patients who had "sham" arthroscopic surgery (general anesthesia was given and superficial incisions were made in the skin, but no actual surgical repair was performed) reported as much pain relief and improved mobility as patients who underwent the actual procedure. At the time of the study, more than 650,000 knee operations had been performed annually at a cost of $5,000 each.
In other words, billions were spent on a surgical procedure that hadn't undergone a decent controlled study against placebo -- the same criticism often leveled by CAM skeptics. At least glucosamine doesn't have the known serious side effects associated with unnecessary surgery.

The placebo effect has maddened the medical world for generations. But recent advances in brain imaging emphasize for me that “placebo” should not be regarded a dirty word. In fact, it is time to give placebo a new image and update its beneficial role in our modern medical armamentarium.

Folk psychology tells us that the placebo effect is, in large part, a function of patient suggestibility and that some of us are clearly more suggestible than others. For centuries, physicians have handed out inert colored water and sugar pills with the full knowledge that approximately a third of their patients will report feeling better. We assume that the degree of response is somehow a reflection of the psychological state of the patient -- the greater the degree of gullibility, the more likely he or she is to believe that a sugar pill will relieve aches and pains. But there's an unanticipated side effect of this assumption.

Attributing the placebo effect to gullibility is a subtle accusation of a patient's weakness and lack of sophistication. I suspect that many of us consciously or unconsciously look down upon those who are good placebo responders, as though you have to be a real dummy to believe everything the doctor tells or gives you.

But placebo serves a very real evolutionary function. At a time when there were no medicines, the placebo effect was all that stood between primitive humans and the agonies of injuries and illnesses. A look at the functional imaging scans shows how truly robust are the involved brain systems. These systems are here to stay. Even given our advanced state of medical knowledge, much of routine medical care -- from treating backaches to the common cold -- relies primarily upon reassurance and hope, not disease-specific treatments.

Given the choice, we'd all prefer to be placebo responders, though none of us want to be categorized as rubes. We complain about not getting enough quality time with our doctors, yet would never dream of directly asking for a prescription for a placebo. Instead, if we believe in conventional (allopathic) medicine, we might ask for an antibiotic for the common cold, with the rationale that, yes, it's only a virus, but perhaps the antibiotic will help. If we are inclined toward alternative medical treatments, we will plunk down a few bucks for a bottle of echinacea or a pack of zinc lozenges. To the extent that we feel better, we have invoked the placebo effect.

Keep in mind that whenever there is no specific well-substantiated treatment for a condition, the only alternative to glum acceptance and the proverbial stiff upper lip is to seek out a placebo. But don't tell us it's a placebo. Don't even hint that we are self-deluded suckers who might spring for a case of snake oil or a six-pack of eye of newt. Just as religion softens the blow of facing death, placebo softens the blow of facing life.

It's no wonder that CAM is so popular. In her recent book, "The Cure Within: A History of Mind-Body Medicine," Harvard chairwoman of history of science Anne Harrington outlines the various narratives that have historically contributed to the placebo response's role in CAM. She points out that the belief in positive thinking and maintaining personal self-control push us into making our own health choices, irrespective of their scientific validity.

She also emphasizes another increasingly popular Western narrative -- the "broken by modern life" tale of woe, anger and rebellion. It cannot be overstated that a medical system that feels and appears unfriendly will be abandoned in favor of one that does not, even if the supporting evidence isn't there. The urge for comfort is greater than an insistence upon objectivity. Even if glucosamine isn't demonstrably helpful for garden-variety arthritis, it will be a bestseller until a real treatment is found.

Again and again, the same problem applies to conventional medicine. Even some of the best-designed trials run headlong into the hidden power of the placebo. Consider the data from a 2002 review of trials on the six leading antidepressants, including Prozac, Zoloft and Effexor. Of the 47 trials, 27 showed the antidepressants to have no greater benefit than the placebo control group. According to the lead author, Irving Kirsch of the University of Connecticut, the remaining 20 showed improvements of dubious clinical significance.

In fact, evaluating any new treatment for a condition that must be subjectively evaluated -- pain, mood change, quality of life -- runs into the same problem. Whether looking at drugs for attention-deficit hyperactivity disorder or for mental illnesses such as bipolar disorder and schizophrenia, or simply determining if a drug can modify the behavioral manifestations of Alzheimer's disease, we are at the mercy of how to adequately contain and measure the placebo effect -- an impossibly complex task with serious ethical implications

 

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