575 lines
31 KiB
Markdown
575 lines
31 KiB
Markdown
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created_at: '2011-09-19T22:32:28.000Z'
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title: Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why (2009)
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url: http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all
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author: adammichaelc
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points: 139
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story_text: ''
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comment_text:
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num_comments: 61
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story_id:
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story_title:
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story_url:
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parent_id:
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created_at_i: 1316471548
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_tags:
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- story
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- author_adammichaelc
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- story_3015479
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objectID: '3015479'
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year: 2009
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---
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[![](https://www.wired.com/wp-content/uploads/archive/images/article/magazine/1709/ff_placebo_effect_f.jpg)](https://www.wired.com/medtech/drugs/magazine/17-09/#)
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\* Photo: Nick Veasey \* **Merck was in trouble.** In 2002, the
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pharmaceutical giant was falling behind its rivals in sales. Even worse,
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patents on five blockbuster drugs were about to expire, which would
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allow cheaper generics to flood the market. The company hadn't
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introduced a truly new product in three years, and its stock price was
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plummeting.
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In interviews with the press, Edward Scolnick, Merck's research
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director, laid out his battle plan to restore the firm to preeminence.
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Key to his strategy was expanding the company's reach into the
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antidepressant market, where Merck had lagged while competitors like
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Pfizer and GlaxoSmithKline created some of the best-selling drugs in the
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world. "To remain dominant in the future," he told Forbes, "we need to
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dominate the central nervous system."
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His plan hinged on the success of an experimental antidepressant
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codenamed MK-869. Still in clinical trials, it looked like every pharma
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executive's dream: a new kind of medication that exploited brain
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chemistry in innovative ways to promote feelings of well-being. The drug
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tested brilliantly early on, with minimal side effects, and Merck touted
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its game-changing potential at a meeting of 300 securities analysts.
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Behind the scenes, however, MK-869 was starting to unravel. True, many
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test subjects treated with the medication felt their hopelessness and
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anxiety lift. But so did nearly the same number who took a placebo, a
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look-alike pill made of milk sugar or another inert substance given to
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groups of volunteers in clinical trials to gauge how much more effective
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the real drug is by comparison. The fact that taking a faux drug can
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powerfully improve some people's health—the so-called placebo effect—has
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long been considered an embarrassment to the serious practice of
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pharmacology.
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Ultimately, Merck's foray into the antidepressant market failed. In
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subsequent tests, MK-869 turned out to be no more effective than a
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placebo. In the jargon of the industry, the trials crossed the futility
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boundary.
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MK-869 wasn't the only highly anticipated medical breakthrough to be
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undone in recent years by the placebo effect. From 2001 to 2006, the
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percentage of new products cut from development after Phase II clinical
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trials, when drugs are first tested against placebo, rose by 20 percent.
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The failure rate in more extensive Phase III trials increased by 11
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percent, mainly due to surprisingly poor showings against placebo.
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Despite historic levels of industry investment in R\&D, the US Food and
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Drug Administration approved only 19 first-of-their-kind remedies in
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2007—the fewest since 1983—and just 24 in 2008. Half of all drugs that
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fail in late-stage trials drop out of the pipeline due to their
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inability to beat sugar pills.
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The upshot is fewer new medicines available to ailing patients and more
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financial woes for the beleaguered pharmaceutical industry. Last
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November, a new type of gene therapy for Parkinson's disease, championed
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by the Michael J. Fox Foundation, was abruptly withdrawn from Phase II
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trials after unexpectedly tanking against placebo. A stem-cell startup
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called Osiris Therapeutics got a drubbing on Wall Street in March, when
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it suspended trials of its pill for Crohn's disease, an intestinal
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ailment, citing an "unusually high" response to placebo. Two days later,
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Eli Lilly broke off testing of a much-touted new drug for schizophrenia
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when volunteers showed double the expected level of placebo response.
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It's not only trials of new drugs that are crossing the futility
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boundary. Some products that have been on the market for decades, like
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Prozac, are faltering in more recent follow-up tests. In many cases,
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these are the compounds that, in the late '90s, made Big Pharma more
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profitable than Big Oil. But if these same drugs were vetted now, the
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FDA might not approve some of them. Two comprehensive analyses of
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antidepressant trials have uncovered a dramatic increase in placebo
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response since the 1980s. One estimated that the so-called effect size
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(a measure of statistical significance) in placebo groups had nearly
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doubled over that time.
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It's not that the old meds are getting weaker, drug developers say. It's
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as if the placebo effect is somehow getting stronger.
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The fact that an increasing number of medications are unable to beat
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sugar pills has thrown the industry into crisis. The stakes could hardly
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be higher. In today's economy, the fate of a long-established company
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can hang on the outcome of a handful of tests.
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Why are inert pills suddenly overwhelming promising new drugs and
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established medicines alike? The reasons are only just beginning to be
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understood. A network of independent researchers is doggedly uncovering
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the inner workings—and potential therapeutic applications—of the placebo
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effect. At the same time, drugmakers are realizing they need to fully
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understand the mechanisms behind it so they can design trials that
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differentiate more clearly between the beneficial effects of their
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products and the body's innate ability to heal itself. A special task
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force of the Foundation for the National Institutes of Health is seeking
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to stem the crisis by quietly undertaking one of the most ambitious
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data-sharing efforts in the history of the drug industry. After decades
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in the jungles of fringe science, the placebo effect has become the
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elephant in the boardroom.
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**The roots of the** placebo problem can be traced to a lie told by an
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Army nurse during World War II as Allied forces stormed the beaches of
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southern Italy. The nurse was assisting an anesthetist named Henry
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Beecher, who was tending to US troops under heavy German bombardment.
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When the morphine supply ran low, the nurse assured a wounded soldier
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that he was getting a shot of potent painkiller, though her syringe
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contained only salt water. Amazingly, the bogus injection relieved the
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soldier's agony and prevented the onset of shock.
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Returning to his post at Harvard after the war, Beecher became one of
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the nation's leading medical reformers. Inspired by the nurse's healing
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act of deception, he launched a crusade to promote a method of testing
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new medicines to find out whether they were truly effective. At the
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time, the process for vetting drugs was sloppy at best: Pharmaceutical
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companies would simply dose volunteers with an experimental agent until
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the side effects swamped the presumed benefits. Beecher proposed that if
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test subjects could be compared to a group that received a placebo,
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health officials would finally have an impartial way to determine
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whether a medicine was actually responsible for making a patient
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better.
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![](https://www.wired.com/wp-content/uploads/archive/images/article/magazine/1709/ff_placebo_effect2_f.jpg)In
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a 1955 paper titled "The Powerful Placebo," published in The Journal of
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the American Medical Association, Beecher described how the placebo
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effect had undermined the results of more than a dozen trials by causing
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improvement that was mistakenly attributed to the drugs being tested. He
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demonstrated that trial volunteers who got real medication were also
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subject to placebo effects; the act of taking a pill was itself somehow
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therapeutic, boosting the curative power of the medicine. Only by
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subtracting the improvement in a placebo control group could the actual
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value of the drug be calculated.
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The article caused a sensation. By 1962, reeling from news of birth
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defects caused by a drug called thalidomide, Congress amended the Food,
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Drug, and Cosmetic Act, requiring trials to include enhanced safety
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testing and placebo control groups. Volunteers would be assigned
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randomly to receive either medicine or a sugar pill, and neither doctor
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nor patient would know the difference until the trial was over.
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Beecher's double-blind, placebo-controlled, randomized clinical trial—or
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RCT—was enshrined as the gold standard of the emerging pharmaceutical
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industry. Today, to win FDA approval, a new medication must beat placebo
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in at least two authenticated trials.
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Beecher's prescription helped cure the medical establishment of outright
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quackery, but it had an insidious side effect. By casting placebo as the
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villain in RCTs, he ended up stigmatizing one of his most important
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discoveries. The fact that even dummy capsules can kick-start the body's
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recovery engine became a problem for drug developers to overcome, rather
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than a phenomenon that could guide doctors toward a better understanding
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of the healing process and how to drive it most effectively.
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In his eagerness to promote his template for clinical trials, Beecher
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also overreached by seeing the placebo effect at work in curing ailments
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like the common cold, which wane with no intervention at all. But the
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triumph of Beecher's gold standard was a generation of safer medications
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that worked for nearly everyone. Anthracyclines don't require an
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oncologist with a genial bedside manner to slow the growth of tumors.
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What Beecher didn't foresee, however, was the explosive growth of the
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pharmaceutical industry. The blockbuster success of mood drugs in the
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'80s and '90s emboldened Big Pharma to promote remedies for a growing
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panoply of disorders that are intimately related to higher brain
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function. By attempting to dominate the central nervous system, Big
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Pharma gambled its future on treating ailments that have turned out to
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be particularly susceptible to the placebo effect.
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**The tall, rusty-haired son** of a country doctor, William Potter, 64,
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has spent most of his life treating mental illness—first as a
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psychiatrist at the National Institute of Mental Health and then as a
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drug developer. A decade ago, he took a job at Lilly's neuroscience
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labs. There, working on new antidepressants and antianxiety meds, he
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became one of the first researchers to glimpse the approaching storm.
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To test products internally, pharmaceutical companies routinely run
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trials in which a long-established medication and an experimental one
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compete against each other as well as against a placebo. As head of
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Lilly's early-stage psychiatric drug development in the late '90s,
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Potter saw that even durable warhorses like Prozac, which had been on
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the market for years, were being overtaken by dummy pills in more recent
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tests. The company's next-generation antidepressants were faring badly,
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too, doing no better than placebo in seven out of 10 trials.
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As a psychiatrist, Potter knew that some patients really do seem to get
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healthier for reasons that have more to do with a doctor's empathy than
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with the contents of a pill. But it baffled him that drugs he'd been
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prescribing for years seemed to be struggling to prove their
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effectiveness. Thinking that something crucial may have been overlooked,
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Potter tapped an IT geek named David DeBrota to help him comb through
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the Lilly database of published and unpublished trials—including those
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that the company had kept secret because of high placebo response. They
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aggregated the findings from decades of antidepressant trials, looking
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for patterns and trying to see what was changing over time. What they
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found challenged some of the industry's basic assumptions about its
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drug-vetting process.
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Assumption number one was that if a trial were managed correctly, a
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medication would perform as well or badly in a Phoenix hospital as in a
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Bangalore clinic. Potter discovered, however, that geographic location
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alone could determine whether a drug bested placebo or crossed the
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futility boundary. By the late '90s, for example, the classic
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antianxiety drug diazepam (also known as Valium) was still beating
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placebo in France and Belgium. But when the drug was tested in the US,
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it was likely to fail. Conversely, Prozac performed better in America
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than it did in western Europe and South Africa. It was an unsettling
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prospect: FDA approval could hinge on where the company chose to conduct
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a trial.
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Mistaken assumption number two was that the standard tests used to gauge
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volunteers' improvement in trials yielded consistent results. Potter and
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his colleagues discovered that ratings by trial observers varied
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significantly from one testing site to another. It was like finding out
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that the judges in a tight race each had a different idea about the
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placement of the finish line.
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Potter and DeBrota's data-mining also revealed that even superbly
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managed trials were subject to runaway placebo effects. But exactly why
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any of this was happening remained elusive. "We were able to identify
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many of the core issues in play," Potter says. "But there was no clear
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answer to the problem." Convinced that what Lilly was facing was too
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complex for any one pharmaceutical house to unravel on its own, he came
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up with a plan to break down the firewalls between researchers across
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the industry, enabling them to share data in "pre-competitive space."
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After prodding by Potter and others, the NIH focused on the issue in
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2000, hosting a three-day conference in Washington. For the first time
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in medical history, more than 500 drug developers, doctors, academics,
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and trial designers put their heads together to examine the role of the
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placebo effect in clinical trials and healing in general.
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Potter's ambitious plan for a collaborative approach to the problem
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eventually ran into its own futility boundary: No one would pay for it.
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And drug companies don't share data, they hoard it. But the NIH
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conference launched a new wave of placebo research in academic labs in
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the US and Italy that would make significant progress toward solving the
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mystery of what was happening in clinical trials.
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**Visitors to Fabrizio** Benedetti's clinic at the University of Turin
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are asked never to say the P-word around the med students who sign up
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for his experiments. For all the volunteers know, the trim, soft-spoken
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neuroscientist is hard at work concocting analgesic skin creams and
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methods for enhancing athletic performance.
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One recent afternoon in his lab, a young soccer player grimaced with
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exertion while doing leg curls on a weight machine. Benedetti and his
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colleagues were exploring the potential of using Pavlovian conditioning
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to give athletes a competitive edge undetectable by anti-doping
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authorities. A player would receive doses of a performance-enhancing
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drug for weeks and then a jolt of placebo just before competition.
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Benedetti, 53, first became interested in placebos in the mid-'90s,
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while researching pain. He was surprised that some of the test subjects
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in his placebo groups seemed to suffer less than those on active drugs.
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But scientific interest in this phenomenon, and the money to research
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it, were hard to come by. "The placebo effect was considered little more
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than a nuisance," he recalls. "Drug companies, physicians, and
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clinicians were not interested in understanding its mechanisms. They
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were concerned only with figuring out whether their drugs worked
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better."
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Part of the problem was that response to placebo was considered a
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psychological trait related to neurosis and gullibility rather than a
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physiological phenomenon that could be scrutinized in the lab and
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manipulated for therapeutic benefit. But then Benedetti came across a
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study, done years earlier, that suggested the placebo effect had a
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neurological foundation. US scientists had found that a drug called
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naloxone blocks the pain-relieving power of placebo treatments. The
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brain produces its own analgesic compounds called opioids, released
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under conditions of stress, and naloxone blocks the action of these
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natural painkillers and their synthetic analogs. The study gave
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Benedetti the lead he needed to pursue his own research while running
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small clinical trials for drug companies.
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Now, after 15 years of experimentation, he has succeeded in mapping many
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of the biochemical reactions responsible for the placebo effect,
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uncovering a broad repertoire of self-healing responses.
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Placebo-activated opioids, for example, not only relieve pain; they also
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modulate heart rate and respiration. The neurotransmitter dopamine, when
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released by placebo treatment, helps improve motor function in
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Parkinson's patients. Mechanisms like these can elevate mood, sharpen
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cognitive ability, alleviate digestive disorders, relieve insomnia, and
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limit the secretion of stress-related hormones like insulin and
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cortisol.
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In one study, Benedetti found that Alzheimer's patients with impaired
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cognitive function get less pain relief from analgesic drugs than normal
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volunteers do. Using advanced methods of EEG analysis, he discovered
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that the connections between the patients' prefrontal lobes and their
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opioid systems had been damaged. Healthy volunteers feel the benefit of
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medication plus a placebo boost. Patients who are unable to formulate
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ideas about the future because of cortical deficits, however, feel only
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the effect of the drug itself. The experiment suggests that because
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Alzheimer's patients don't get the benefits of anticipating the
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treatment, they require higher doses of painkillers to experience normal
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levels of relief.
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Benedetti often uses the phrase "placebo response" instead of placebo
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effect. By definition, inert pills have no effect, but under the right
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conditions they can act as a catalyst for what he calls the body's
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"endogenous health care system." Like any other internal network, the
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placebo response has limits. It can ease the discomfort of chemotherapy,
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but it won't stop the growth of tumors. It also works in reverse to
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produce the placebo's evil twin, the nocebo effect. For example, men
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taking a commonly prescribed prostate drug who were informed that the
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medication may cause sexual dysfunction were twice as likely to become
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impotent.
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Further research by Benedetti and others showed that the promise of
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treatment activates areas of the brain involved in weighing the
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significance of events and the seriousness of threats. "If a fire alarm
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goes off and you see smoke, you know something bad is going to happen
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and you get ready to escape," explains Tor Wager, a neuroscientist at
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Columbia University. "Expectations about pain and pain relief work in a
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similar way. Placebo treatments tap into this system and orchestrate the
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responses in your brain and body accordingly."
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In other words, one way that placebo aids recovery is by hacking the
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mind's ability to predict the future. We are constantly parsing the
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reactions of those around us—such as the tone a doctor uses to deliver a
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diagnosis—to generate more-accurate estimations of our fate. One of the
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most powerful placebogenic triggers is watching someone else experience
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the benefits of an alleged drug. Researchers call these social aspects
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of medicine the therapeutic ritual.
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In a study last year, Harvard Medical School researcher Ted Kaptchuk
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devised a clever strategy for testing his volunteers' response to
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varying levels of therapeutic ritual. The study focused on irritable
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bowel syndrome, a painful disorder that costs more than $40 billion a
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year worldwide to treat. First the volunteers were placed randomly in
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one of three groups. One group was simply put on a waiting list;
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researchers know that some patients get better just because they sign up
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for a trial. Another group received placebo treatment from a clinician
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who declined to engage in small talk. Volunteers in the third group got
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the same sham treatment from a clinician who asked them questions about
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symptoms, outlined the causes of IBS, and displayed optimism about their
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condition.
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**Rx for Success**——————
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What turns a dummy pill into a catalyst for relieving pain, anxiety,
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depression, sexual dysfunction, or the tremors of Parkinson's disease?
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The brain's own healing mechanisms, unleashed by the belief that a phony
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medication is the real thing. The most important ingredient in any
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placebo is the doctor's bedside manner, but according to research, the
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color of a tablet can boost the effectiveness even of genuine meds—or
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help convince a patient that a placebo is a potent remedy.—Steve
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Silberman
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![](/images/article/magazine/1709/ff_placebo_effect3_f.jpg)**Yellow
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pills**
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make the most effective antidepressants, like little doses of
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pharmaceutical sunshine.
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![](/images/article/magazine/1709/ff_placebo_effect4_f.jpg)**Red
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pills**
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can give you a more stimulating kick. Wake up, Neo.
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![](/images/article/magazine/1709/ff_placebo_effect5_f.jpg)**The color
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green**
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reduces anxiety, adding more chill to the pill.
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![](/images/article/magazine/1709/ff_placebo_effect6_f.jpg)**White
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tablets**—
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particularly those labeled "antacid"—are superior for soothing ulcers,
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even when they contain nothing but lactose.
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![](/images/article/magazine/1709/ff_placebo_effect7_f.jpg)**More is
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better,**
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scientists say. Placebos taken four times a day deliver greater relief
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than those taken twice daily.
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![](/images/article/magazine/1709/ff_placebo_effect8_f.jpg)**Branding
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matters.**
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Placebos stamped or packaged with widely recognized trademarks are more
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effective than "generic" placebos.
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![](/images/article/magazine/1709/ff_placebo_effect9_f.jpg)**Clever
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names**
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can add a placebo boost to the physiological punch in real drugs. Viagra
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implies both vitality and an unstoppable Niagara of sexy.
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Not surprisingly, the health of those in the third group improved most.
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In fact, just by participating in the trial, volunteers in this
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high-interaction group got as much relief as did people taking the two
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leading prescription drugs for IBS. And the benefits of their bogus
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treatment persisted for weeks afterward, contrary to the
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belief—widespread in the pharmaceutical industry—that the placebo
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response is short-lived.
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Studies like this open the door to hybrid treatment strategies that
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exploit the placebo effect to make real drugs safer and more effective.
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Cancer patients undergoing rounds of chemotherapy often suffer from
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debilitating nocebo effects—such as anticipatory nausea—conditioned by
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their past experiences with the drugs. A team of German researchers has
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shown that these associations can be unlearned through the
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administration of placebo, making chemo easier to bear.
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Meanwhile, the classic use of placebos in medicine—to boost the
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confidence of anxious patients—has been employed tacitly for ages.
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Nearly half of the doctors polled in a 2007 survey in Chicago admitted
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to prescribing medications they knew were ineffective for a patient's
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condition—or prescribing effective drugs in doses too low to produce
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actual benefit—in order to provoke a placebo response.
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The main objections to more widespread placebo use in clinical practice
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are ethical, but the solutions to these conundrums can be surprisingly
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simple. Investigators told volunteers in one placebo study that the
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pills they were taking were "known to significantly reduce pain in some
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patients." The researchers weren't lying.
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**These new findings** tell us that the body's response to certain types
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of medication is in constant flux, affected by expectations of
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treatment, conditioning, beliefs, and social cues.
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|
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For instance, the geographic variations in trial outcome that Potter
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uncovered begin to make sense in light of discoveries that the placebo
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|
response is highly sensitive to cultural differences. Anthropologist
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Daniel Moerman found that Germans are high placebo reactors in trials of
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|
ulcer drugs but low in trials of drugs for hypertension—an undertreated
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|
condition in Germany, where many people pop pills for herzinsuffizienz,
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|
or low blood pressure. Moreover, a pill's shape, size, branding, and
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|
price all influence its effects on the body. Soothing blue capsules make
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|
more effective tranquilizers than angry red ones, except among Italian
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|
men, for whom the color blue is associated with their national soccer
|
|
team—Forza Azzurri\!
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|
|
|
But why would the placebo effect seem to be getting stronger worldwide?
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|
Part of the answer may be found in the drug industry's own success in
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|
marketing its products.
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|
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|
Potential trial volunteers in the US have been deluged with ads for
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|
prescription medications since 1997, when the FDA amended its policy on
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|
direct-to-consumer advertising. The secret of running an effective
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|
campaign, Saatchi & Saatchi's Jim Joseph told a trade journal last year,
|
|
is associating a particular brand-name medication with other aspects of
|
|
life that promote peace of mind: "Is it time with your children? Is it a
|
|
good book curled up on the couch? Is it your favorite television show?
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|
Is it a little purple pill that helps you get rid of acid reflux?" By
|
|
evoking such uplifting associations, researchers say, the ads set up the
|
|
kind of expectations that induce a formidable placebo response.
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|
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|
The success of those ads in selling blockbuster drugs like
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|
antidepressants and statins also pushed trials offshore as therapeutic
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|
virgins—potential volunteers who were not already medicated with one or
|
|
another drug—became harder to find. The contractors that manage trials
|
|
for Big Pharma have moved aggressively into Africa, India, China, and
|
|
the former Soviet Union. In these places, however, cultural dynamics can
|
|
boost the placebo response in other ways. Doctors in these countries are
|
|
paid to fill up trial rosters quickly, which may motivate them to
|
|
recruit patients with milder forms of illness that yield more readily to
|
|
placebo treatment. Furthermore, a patient's hope of getting better and
|
|
expectation of expert care—the primary placebo triggers in the brain—are
|
|
particularly acute in societies where volunteers are clamoring to gain
|
|
access to the most basic forms of medicine. "The quality of care that
|
|
placebo patients get in trials is far superior to the best insurance you
|
|
get in America," says psychiatrist Arif Khan, principal investigator in
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|
hundreds of trials for companies like Pfizer and Bristol-Myers Squibb.
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|
"It's basically luxury care."
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|
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|
Big Pharma faces additional problems in beating placebo when it comes to
|
|
psychiatric drugs. One is to accurately define the nature of mental
|
|
illness. The litmus test of drug efficacy in antidepressant trials is a
|
|
questionnaire called the Hamilton Depression Rating Scale. The HAM-D was
|
|
created nearly 50 years ago based on a study of major depressive
|
|
disorder in patients confined to asylums. Few trial volunteers now
|
|
suffer from that level of illness. In fact, many experts are starting to
|
|
wonder if what drug companies now call depression is even the same
|
|
disease that the HAM-D was designed to diagnose.
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|
|
|
Existing tests also may not be appropriate for diagnosing disorders like
|
|
social anxiety and premenstrual dysphoria—the very types of chronic,
|
|
fuzzily defined conditions that the drug industry started targeting in
|
|
the '90s, when the placebo problem began escalating. The neurological
|
|
foundation of these illnesses is still being debated, making it even
|
|
harder for drug companies to come up with effective treatments.
|
|
|
|
What all of these disorders have in common, however, is that they engage
|
|
the higher cortical centers that generate beliefs and expectations,
|
|
interpret social cues, and anticipate rewards. So do chronic pain,
|
|
sexual dysfunction, Parkinson's, and many other ailments that respond
|
|
robustly to placebo treatment. To avoid investing in failure,
|
|
researchers say, pharmaceutical companies will need to adopt new ways of
|
|
vetting drugs that route around the brain's own centralized network for
|
|
healing.
|
|
|
|
**Ten years and billions** of R\&D dollars after William Potter first
|
|
sounded the alarm about the placebo effect, his message has finally
|
|
gotten through. In the spring, Potter, who is now a VP at Merck, helped
|
|
rev up a massive data-gathering effort called the Placebo Response Drug
|
|
Trials Survey.
|
|
|
|
Under the auspices of the
|
|
FNIH1[1](https://www.wired.com/medtech/drugs/magazine/17-09/#corrections),
|
|
Potter and his colleagues are acquiring decades of trial data—including
|
|
blood and DNA samples—to determine which variables are responsible for
|
|
the apparent rise in the placebo effect. Merck, Lilly, Pfizer,
|
|
AstraZeneca, GlaxoSmithKline, Sanofi-Aventis, Johnson & Johnson, and
|
|
other major firms are funding the study, and the process of scrubbing
|
|
volunteers' names and other personal information from the database is
|
|
about to begin.
|
|
|
|
In typically secretive industry fashion, the existence of the project
|
|
itself is being kept under wraps. FNIH
|
|
staffers2[2](https://www.wired.com/medtech/drugs/magazine/17-09/#corrections)
|
|
are willing to talk about it only anonymously, concerned about offending
|
|
the companies paying for it.
|
|
|
|
For Potter, who used to ride along with his father on house calls in
|
|
Indiana, the significance of the survey goes beyond Big Pharma's finally
|
|
admitting it has a placebo problem. It also marks the twilight of an era
|
|
when the drug industry was confident that its products were strong
|
|
enough to cure illness by themselves.
|
|
|
|
"Before I routinely prescribed antidepressants, I would do more
|
|
psychotherapy for mildly depressed patients," says the veteran of
|
|
hundreds of drug trials. "Today we would say I was trying to engage
|
|
components of the placebo response—and those patients got better. To
|
|
really do the best for your patients, you want the best placebo response
|
|
plus the best drug response."
|
|
|
|
The pharma crisis has also finally brought together the two parallel
|
|
streams of placebo research—academic and industrial. Pfizer has asked
|
|
Fabrizio Benedetti to help the company figure out why two of its pain
|
|
drugs keep failing. Ted Kaptchuk is developing ways to distinguish drug
|
|
response more clearly from placebo response for another pharma house
|
|
that he declines to name. Both are exploring innovative trial models
|
|
that treat the placebo effect as more than just statistical noise
|
|
competing with the active drug.
|
|
|
|
Benedetti has helped design a protocol for minimizing volunteers'
|
|
expectations that he calls "open/hidden." In standard trials, the act of
|
|
taking a pill or receiving an injection activates the placebo response.
|
|
In open/hidden trials, drugs and placebos are given to some test
|
|
subjects in the usual way and to others at random intervals through an
|
|
IV line controlled by a concealed computer. Drugs that work only when
|
|
the patient knows they're being administered are placebos themselves.
|
|
|
|
Ironically, Big Pharma's attempt to dominate the central nervous system
|
|
has ended up revealing how powerful the brain really is. The placebo
|
|
response doesn't care if the catalyst for healing is a triumph of
|
|
pharmacology, a compassionate therapist, or a syringe of salt water. All
|
|
it requires is a reasonable expectation of getting better. That's potent
|
|
medicine.
|
|
|
|
Contributing editor Steve Silberman
|
|
([steve@stevesilberman.com](https://www.wired.com/medtech/drugs/magazine/17-09/mailto:steve@stevesilberman.com))
|
|
wrote about the hunt for Jim Gray in issue 15.08.
|
|
|
|
[Paging Dr. Pan: Placebos Work Better in
|
|
Children](https://www.wired.com/wiredscience/2008/08/paging-dr-pan-p/)
|
|
|
|
[For Back Pain, Even Fake Acupuncture
|
|
Works](https://www.wired.com/wiredscience/2007/09/for-back-pain-e/)
|
|
|
|
[Why Sugar Pills Cure Some
|
|
Ills](https://www.wired.com/medtech/health/news/2004/03/62296)
|
|
|
|
[What We Don't
|
|
Know](https://www.wired.com/wired/archive/15.02/bigquestions.html?pg=3)
|