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  1. Expat98
    Merck was in trouble. In 2002, the pharmaceutical giant was falling behind its rivals in sales. Even worse, patents on five blockbuster drugs were about to expire, which would allow cheaper generics to flood the market. The company hadn't introduced a truly new product in three years, and its stock price was plummeting.

    In interviews with the press, Edward Scolnick, Merck's research director, laid out his battle plan to restore the firm to preeminence. Key to his strategy was expanding the company's reach into the antidepressant market, where Merck had lagged while competitors like Pfizer and GlaxoSmithKline created some of the best-selling drugs in the world. "To remain dominant in the future," he told Forbes, "we need to dominate the central nervous system."

    His plan hinged on the success of an experimental antidepressant codenamed MK-869. Still in clinical trials, it looked like every pharma executive's dream: a new kind of medication that exploited brain chemistry in innovative ways to promote feelings of well-being. The drug tested brilliantly early on, with minimal side effects, and Merck touted its game-changing potential at a meeting of 300 securities analysts.

    Behind the scenes, however, MK-869 was starting to unravel. True, many test subjects treated with the medication felt their hopelessness and anxiety lift. But so did nearly the same number who took a placebo, a look-alike pill made of milk sugar or another inert substance given to groups of volunteers in clinical trials to gauge how much more effective the real drug is by comparison. The fact that taking a faux drug can powerfully improve some people's health—the so-called placebo effect—has long been considered an embarrassment to the serious practice of pharmacology.

    Ultimately, Merck's foray into the antidepressant market failed. In subsequent tests, MK-869 turned out to be no more effective than a placebo. In the jargon of the industry, the trials crossed the futility boundary.

    MK-869 wasn't the only highly anticipated medical breakthrough to be undone in recent years by the placebo effect. From 2001 to 2006, the percentage of new products cut from development after Phase II clinical trials, when drugs are first tested against placebo, rose by 20 percent. The failure rate in more extensive Phase III trials increased by 11 percent, mainly due to surprisingly poor showings against placebo. Despite historic levels of industry investment in R&D, the US Food and Drug Administration approved only 19 first-of-their-kind remedies in 2007—the fewest since 1983—and just 24 in 2008. Half of all drugs that fail in late-stage trials drop out of the pipeline due to their inability to beat sugar pills.

    The upshot is fewer new medicines available to ailing patients and more financial woes for the beleaguered pharmaceutical industry. Last November, a new type of gene therapy for Parkinson's disease, championed by the Michael J. Fox Foundation, was abruptly withdrawn from Phase II trials after unexpectedly tanking against placebo. A stem-cell startup called Osiris Therapeutics got a drubbing on Wall Street in March, when it suspended trials of its pill for Crohn's disease, an intestinal ailment, citing an "unusually high" response to placebo. Two days later, Eli Lilly broke off testing of a much-touted new drug for schizophrenia when volunteers showed double the expected level of placebo response.

    It's not only trials of new drugs that are crossing the futility boundary. Some products that have been on the market for decades, like Prozac, are faltering in more recent follow-up tests. In many cases, these are the compounds that, in the late '90s, made Big Pharma more profitable than Big Oil. But if these same drugs were vetted now, the FDA might not approve some of them. Two comprehensive analyses of antidepressant trials have uncovered a dramatic increase in placebo response since the 1980s. One estimated that the so-called effect size (a measure of statistical significance) in placebo groups had nearly doubled over that time.

    It's not that the old meds are getting weaker, drug developers say. It's as if the placebo effect is somehow getting stronger.

    The fact that an increasing number of medications are unable to beat sugar pills has thrown the industry into crisis. The stakes could hardly be higher. In today's economy, the fate of a long-established company can hang on the outcome of a handful of tests.

    Why are inert pills suddenly overwhelming promising new drugs and established medicines alike? The reasons are only just beginning to be understood. A network of independent researchers is doggedly uncovering the inner workings—and potential therapeutic applications—of the placebo effect. At the same time, drugmakers are realizing they need to fully understand the mechanisms behind it so they can design trials that differentiate more clearly between the beneficial effects of their products and the body's innate ability to heal itself. A special task force of the Foundation for the National Institutes of Health is seeking to stem the crisis by quietly undertaking one of the most ambitious data-sharing efforts in the history of the drug industry. After decades in the jungles of fringe science, the placebo effect has become the elephant in the boardroom.

    The roots of the placebo problem can be traced to a lie told by an Army nurse during World War II as Allied forces stormed the beaches of southern Italy. The nurse was assisting an anesthetist named Henry Beecher, who was tending to US troops under heavy German bombardment. When the morphine supply ran low, the nurse assured a wounded soldier that he was getting a shot of potent painkiller, though her syringe contained only salt water. Amazingly, the bogus injection relieved the soldier's agony and prevented the onset of shock.

    Returning to his post at Harvard after the war, Beecher became one of the nation's leading medical reformers. Inspired by the nurse's healing act of deception, he launched a crusade to promote a method of testing new medicines to find out whether they were truly effective. At the time, the process for vetting drugs was sloppy at best: Pharmaceutical companies would simply dose volunteers with an experimental agent until the side effects swamped the presumed benefits. Beecher proposed that if test subjects could be compared to a group that received a placebo, health officials would finally have an impartial way to determine whether a medicine was actually responsible for making a patient better.

    In a 1955 paper titled "The Powerful Placebo," published in The Journal of the American Medical Association, Beecher described how the placebo effect had undermined the results of more than a dozen trials by causing improvement that was mistakenly attributed to the drugs being tested. He demonstrated that trial volunteers who got real medication were also subject to placebo effects; the act of taking a pill was itself somehow therapeutic, boosting the curative power of the medicine. Only by subtracting the improvement in a placebo control group could the actual value of the drug be calculated.

    The article caused a sensation. By 1962, reeling from news of birth defects caused by a drug called thalidomide, Congress amended the Food, Drug, and Cosmetic Act, requiring trials to include enhanced safety testing and placebo control groups. Volunteers would be assigned randomly to receive either medicine or a sugar pill, and neither doctor nor patient would know the difference until the trial was over. Beecher's double-blind, placebo-controlled, randomized clinical trial—or RCT—was enshrined as the gold standard of the emerging pharmaceutical industry. Today, to win FDA approval, a new medication must beat placebo in at least two authenticated trials.

    Beecher's prescription helped cure the medical establishment of outright quackery, but it had an insidious side effect. By casting placebo as the villain in RCTs, he ended up stigmatizing one of his most important discoveries. The fact that even dummy capsules can kick-start the body's recovery engine became a problem for drug developers to overcome, rather than a phenomenon that could guide doctors toward a better understanding of the healing process and how to drive it most effectively.

    In his eagerness to promote his template for clinical trials, Beecher also overreached by seeing the placebo effect at work in curing ailments like the common cold, which wane with no intervention at all. But the triumph of Beecher's gold standard was a generation of safer medications that worked for nearly everyone. Anthracyclines don't require an oncologist with a genial bedside manner to slow the growth of tumors.

    What Beecher didn't foresee, however, was the explosive growth of the pharmaceutical industry. The blockbuster success of mood drugs in the '80s and '90s emboldened Big Pharma to promote remedies for a growing panoply of disorders that are intimately related to higher brain function. By attempting to dominate the central nervous system, Big Pharma gambled its future on treating ailments that have turned out to be particularly susceptible to the placebo effect.

    The tall, rusty-haired son of a country doctor, William Potter, 64, has spent most of his life treating mental illness—first as a psychiatrist at the National Institute of Mental Health and then as a drug developer. A decade ago, he took a job at Lilly's neuroscience labs. There, working on new antidepressants and antianxiety meds, he became one of the first researchers to glimpse the approaching storm.

    To test products internally, pharmaceutical companies routinely run trials in which a long-established medication and an experimental one compete against each other as well as against a placebo. As head of Lilly's early-stage psychiatric drug development in the late '90s, Potter saw that even durable warhorses like Prozac, which had been on the market for years, were being overtaken by dummy pills in more recent tests. The company's next-generation antidepressants were faring badly, too, doing no better than placebo in seven out of 10 trials.

    As a psychiatrist, Potter knew that some patients really do seem to get healthier for reasons that have more to do with a doctor's empathy than with the contents of a pill. But it baffled him that drugs he'd been prescribing for years seemed to be struggling to prove their effectiveness. Thinking that something crucial may have been overlooked, Potter tapped an IT geek named David DeBrota to help him comb through the Lilly database of published and unpublished trials—including those that the company had kept secret because of high placebo response. They aggregated the findings from decades of antidepressant trials, looking for patterns and trying to see what was changing over time. What they found challenged some of the industry's basic assumptions about its drug-vetting process.

    Assumption number one was that if a trial were managed correctly, a medication would perform as well or badly in a Phoenix hospital as in a Bangalore clinic. Potter discovered, however, that geographic location alone could determine whether a drug bested placebo or crossed the futility boundary. By the late '90s, for example, the classic antianxiety drug diazepam (also known as Valium) was still beating placebo in France and Belgium. But when the drug was tested in the US, it was likely to fail. Conversely, Prozac performed better in America than it did in western Europe and South Africa. It was an unsettling prospect: FDA approval could hinge on where the company chose to conduct a trial.

    Mistaken assumption number two was that the standard tests used to gauge volunteers' improvement in trials yielded consistent results. Potter and his colleagues discovered that ratings by trial observers varied significantly from one testing site to another. It was like finding out that the judges in a tight race each had a different idea about the placement of the finish line.

    Potter and DeBrota's data-mining also revealed that even superbly managed trials were subject to runaway placebo effects. But exactly why any of this was happening remained elusive. "We were able to identify many of the core issues in play," Potter says. "But there was no clear answer to the problem." Convinced that what Lilly was facing was too complex for any one pharmaceutical house to unravel on its own, he came up with a plan to break down the firewalls between researchers across the industry, enabling them to share data in "pre-competitive space."

    After prodding by Potter and others, the NIH focused on the issue in 2000, hosting a three-day conference in Washington. For the first time in medical history, more than 500 drug developers, doctors, academics, and trial designers put their heads together to examine the role of the placebo effect in clinical trials and healing in general.

    Potter's ambitious plan for a collaborative approach to the problem eventually ran into its own futility boundary: No one would pay for it. And drug companies don't share data, they hoard it. But the NIH conference launched a new wave of placebo research in academic labs in the US and Italy that would make significant progress toward solving the mystery of what was happening in clinical trials.

    Visitors to Fabrizio Benedetti's clinic at the University of Turin are asked never to say the P-word around the med students who sign up for his experiments. For all the volunteers know, the trim, soft-spoken neuroscientist is hard at work concocting analgesic skin creams and methods for enhancing athletic performance.

    One recent afternoon in his lab, a young soccer player grimaced with exertion while doing leg curls on a weight machine. Benedetti and his colleagues were exploring the potential of using Pavlovian conditioning to give athletes a competitive edge undetectable by anti-doping authorities. A player would receive doses of a performance-enhancing drug for weeks and then a jolt of placebo just before competition.

    Benedetti, 53, first became interested in placebos in the mid-'90s, while researching pain. He was surprised that some of the test subjects in his placebo groups seemed to suffer less than those on active drugs. But scientific interest in this phenomenon, and the money to research it, were hard to come by. "The placebo effect was considered little more than a nuisance," he recalls. "Drug companies, physicians, and clinicians were not interested in understanding its mechanisms. They were concerned only with figuring out whether their drugs worked better."

    Part of the problem was that response to placebo was considered a psychological trait related to neurosis and gullibility rather than a physiological phenomenon that could be scrutinized in the lab and manipulated for therapeutic benefit. But then Benedetti came across a study, done years earlier, that suggested the placebo effect had a neurological foundation. US scientists had found that a drug called naloxone blocks the pain-relieving power of placebo treatments. The brain produces its own analgesic compounds called opioids, released under conditions of stress, and naloxone blocks the action of these natural painkillers and their synthetic analogs. The study gave Benedetti the lead he needed to pursue his own research while running small clinical trials for drug companies.

    Now, after 15 years of experimentation, he has succeeded in mapping many of the biochemical reactions responsible for the placebo effect, uncovering a broad repertoire of self-healing responses. Placebo-activated opioids, for example, not only relieve pain; they also modulate heart rate and respiration. The neurotransmitter dopamine, when released by placebo treatment, helps improve motor function in Parkinson's patients. Mechanisms like these can elevate mood, sharpen cognitive ability, alleviate digestive disorders, relieve insomnia, and limit the secretion of stress-related hormones like insulin and cortisol.

    In one study, Benedetti found that Alzheimer's patients with impaired cognitive function get less pain relief from analgesic drugs than normal volunteers do. Using advanced methods of EEG analysis, he discovered that the connections between the patients' prefrontal lobes and their opioid systems had been damaged. Healthy volunteers feel the benefit of medication plus a placebo boost. Patients who are unable to formulate ideas about the future because of cortical deficits, however, feel only the effect of the drug itself. The experiment suggests that because Alzheimer's patients don't get the benefits of anticipating the treatment, they require higher doses of painkillers to experience normal levels of relief.

    Benedetti often uses the phrase "placebo response" instead of placebo effect. By definition, inert pills have no effect, but under the right conditions they can act as a catalyst for what he calls the body's "endogenous health care system." Like any other internal network, the placebo response has limits. It can ease the discomfort of chemotherapy, but it won't stop the growth of tumors. It also works in reverse to produce the placebo's evil twin, the nocebo effect. For example, men taking a commonly prescribed prostate drug who were informed that the medication may cause sexual dysfunction were twice as likely to become impotent.

    Further research by Benedetti and others showed that the promise of treatment activates areas of the brain involved in weighing the significance of events and the seriousness of threats. "If a fire alarm goes off and you see smoke, you know something bad is going to happen and you get ready to escape," explains Tor Wager, a neuroscientist at Columbia University. "Expectations about pain and pain relief work in a similar way. Placebo treatments tap into this system and orchestrate the responses in your brain and body accordingly."

    In other words, one way that placebo aids recovery is by hacking the mind's ability to predict the future. We are constantly parsing the reactions of those around us—such as the tone a doctor uses to deliver a diagnosis—to generate more-accurate estimations of our fate. One of the most powerful placebogenic triggers is watching someone else experience the benefits of an alleged drug. Researchers call these social aspects of medicine the therapeutic ritual.

    In a study last year, Harvard Medical School researcher Ted Kaptchuk devised a clever strategy for testing his volunteers' response to varying levels of therapeutic ritual. The study focused on irritable bowel syndrome, a painful disorder that costs more than $40 billion a year worldwide to treat. First the volunteers were placed randomly in one of three groups. One group was simply put on a waiting list; researchers know that some patients get better just because they sign up for a trial. Another group received placebo treatment from a clinician who declined to engage in small talk. Volunteers in the third group got the same sham treatment from a clinician who asked them questions about symptoms, outlined the causes of IBS, and displayed optimism about their condition.

    Not surprisingly, the health of those in the third group improved most. In fact, just by participating in the trial, volunteers in this high-interaction group got as much relief as did people taking the two leading prescription drugs for IBS. And the benefits of their bogus treatment persisted for weeks afterward, contrary to the belief—widespread in the pharmaceutical industry—that the placebo response is short-lived.

    Studies like this open the door to hybrid treatment strategies that exploit the placebo effect to make real drugs safer and more effective. Cancer patients undergoing rounds of chemotherapy often suffer from debilitating nocebo effects—such as anticipatory nausea—conditioned by their past experiences with the drugs. A team of German researchers has shown that these associations can be unlearned through the administration of placebo, making chemo easier to bear.

    Meanwhile, the classic use of placebos in medicine—to boost the confidence of anxious patients—has been employed tacitly for ages. Nearly half of the doctors polled in a 2007 survey in Chicago admitted to prescribing medications they knew were ineffective for a patient's condition—or prescribing effective drugs in doses too low to produce actual benefit—in order to provoke a placebo response.

    The main objections to more widespread placebo use in clinical practice are ethical, but the solutions to these conundrums can be surprisingly simple. Investigators told volunteers in one placebo study that the pills they were taking were "known to significantly reduce pain in some patients." The researchers weren't lying.

    These new findings tell us that the body's response to certain types of medication is in constant flux, affected by expectations of treatment, conditioning, beliefs, and social cues.

    For instance, the geographic variations in trial outcome that Potter uncovered begin to make sense in light of discoveries that the placebo response is highly sensitive to cultural differences. Anthropologist Daniel Moerman found that Germans are high placebo reactors in trials of ulcer drugs but low in trials of drugs for hypertension—an undertreated condition in Germany, where many people pop pills for herzinsuffizienz, or low blood pressure. Moreover, a pill's shape, size, branding, and price all influence its effects on the body. Soothing blue capsules make more effective tranquilizers than angry red ones, except among Italian men, for whom the color blue is associated with their national soccer team—Forza Azzurri!

    But why would the placebo effect seem to be getting stronger worldwide? Part of the answer may be found in the drug industry's own success in marketing its products.

    Potential trial volunteers in the US have been deluged with ads for prescription medications since 1997, when the FDA amended its policy on direct-to-consumer advertising. The secret of running an effective 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? 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.

    The success of those ads in selling blockbuster drugs like antidepressants and statins also pushed trials offshore as therapeutic 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 hundreds of trials for companies like Pfizer and Bristol-Myers Squibb. "It's basically luxury care."

    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.

    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 NIH, 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. NIH staffers 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.

    ---

    By Steve Silberman - WIRED Magazine
    08.24.09

    http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all

Comments

  1. beizebopp
    Wow.. took me a while to read but it was worth it. Really interesting.

    Was it that the placebo is seemingly becoming stronger because more receptive voluenteers are being chosen? I didn't really get that part..

    Now i'm worried that my placebo response will weaken after reaading this :/ :p
  2. Expat98
    That is one of the possible reasons they mention, but I think the main point of the article is that it's kind of a mystery why the placebo effect is getting stronger because the placebo effect itself is so poorly understood. Another possible reason they mention is that it may be due to marketing success. All the pharmaceutical ads people are constantly exposed to are very effective, so people have higher expectations that the drug they're given is going to work. Also, as the medical industy expands more and more, they are starting to target less serious diseases that can be cured just as easily by placebo as by pharmaceutical means.

    The social construction and mental aspects of drug effects is really a complicated and fascinating subject. BTW, the converse of the placebo effect also works: people can become more susceptible to adverse drug side effects by believing that they are more susceptible.
  3. coelho
    Well... swim thinks the pharma industry didnt notice a great way for making a lot of money... if sugar pills are so effective, sell them (without, of couse, mentioning that theyre made of sugar, but that its active compound is called α-D-Glucopyranoside β-D-fructofuranosyl).
    With a nice name, enough publicity and all this results showing its effectiveness for lots of different (and even unrelated) diseases, they could profit enormously with it.

    "Sucrosex - the revolutionary medicine! Very effective for treating anxiety, depression, sexual disfunctions, chronic pain, ulcers, irritable bowel syndrome, Parkinsons disease, schizophrenia, and several other medical conditions! Thousands of trials around the world, during several decades assure its great efficiency! Buy now, for only $ xx.xx !"
  4. Expat98
    ^^They do exactly that with a number of different substances, just not sugar. :)
  5. coelho
    ^^ Thats why swim thought they could do it with sugar... it wouldnt be their first time doing this. ;)
  6. missparkles
    Sparkles thanks the OP, that was an awesome article.
    She thinks it's time to begin to treat the whole body, not just the symptoms of a specific disease. Drugs should never be the only response to health and social problems. Pharma companies have had long enough to prove that drugs are the only answer, now its time to integrate all forms of treatment, take a more holistic approach to illness and disease.
    Sparkles only has one concern, in the rush to discover how placebos work, she hopes patients who would benefit from conventional treatment, are not being denied it. There's something a little deceptive about telling someone with pain they're getting adequate pain meds, when really, they're getting inadequate meds. But an interesting and intriguing subject. Thanks.
    Sparkles.:vibes:
  7. corvardus
    SWIM would have thought that nothing would change. The doctor would have to consider the patients' needs and need to exploit or work around the psychological component. Doctors would be reminded that not everyone is psychologically optimised to exploit the Placebo effect for healing or pain relief and would have to prescribe stronger medications if the lower versions are not up to the task.

    At best a study of this type would open a new field of psychology where the patient is trained to utilise the body's self healing capabilities as part of ongoing treatment with the drugs used as a supplemental effect for healing.
  8. RaverHippie
    Absolutely fantastic article. Interesting to see the testable trials done to understand the endogenous healing processes and how they're initiated. Makes me feel even better that I'm so optimistic about my health.
  9. EscapeDummy
    What an incredible article. This should be required reading for any person who has ever had any sort of health problem. If only more psychiatrists read this...
  10. beizebopp
    I see. In some ways that makes me want to forget all the negative info I know about certain drugs just so that I want encourage them with my placebo response..
    Its all very intriguing stuff. Props for bringing it up.
  11. Nature Boy
    Check out naturopathy. This largely involves selling placebos in the guise of miracle cures. Most of the plants and herbs they sell have no efficacy whatsoever. I don't think it's a good idea to promote the deceptive sale of placebos however. It's entirely unethical and may result in people avoiding proper medication when they are in need of it. Naturopathic remedies are also expensive. They develop a cult-like following whereby many vulnerable individuals are totally sold by it and end up bankrupting themselves in order to knock back fifty, supposedly effective, herbals pills a day. Illegitimate medicine also leads to hysteria where less educated individuals question the validity of reputable, modern medicine. This in itself is not only a crime of ignorance, it is a crime of common decency. Proper medical professionals are hard-working, dedicated people. It is disgraceful that laymen with no scientific or medical training should doubt them so readily.
  12. coelho
    Swim agrees that it isnt a good idea and that it is unethical... he was just being sarcastic... anyway, maybe some pharma industries actually do think it is a good idea... as it was said:

  13. Dickon
    I used to say, partly because I genuinely thought it was a good idea and partly to provoke a response, that trials should be done to see whether a blue placebo was better than a red one. I am delighted to see that someone has taken it upon himself to conduct this research. If one can understand the placebo effect better and optimise it it, it might mean the avoidance of a whole heap of unneeded medical interventions. Sadly this is not in the best interest of big pharma, which makes me sceptical of what studies will be conducted and what results will see the light of day.

    This is one of the most interesting articles I've seen in ages, and I'd suggest people take the time to read it.
  14. alienesseINspace
    Something occurred to me when I read this. I know specifically that the medications I take have a real effect on me. I know this because when I stopped taking them, I tried to act like nothing was wrong. I had never experienced cold turkey withdrawal from an SSRI, benzos, and sleep medication before and had convinced myself that my mind can overcome my former usage.

    After a few months, I was thinking of how to end it all every hour. I would cry randomly. I would fight with my brother...

    I thought "I'm just being moody."

    One night I wanted to throw myself over a balcony and the thought occurred to me "maybe I need to get back on the mental meds."

    So I went to the doctor and started them again.

    Life is completely different. I'm happy and pissed off at times, but not at all suicidal. I feel capable of overcoming hardship.

    I do not believe my meds working indicates a placebo effect because of what it felt like to stop them. I did enjoy reading the article. Thanks for posting it!
  15. Tech House
    Indeed, the effectiveness of placebos does not invalidate the effectiveness of good meds. I doubt a placebo effect could have rid the world of small pox...

    I'm on meds for bipolar disorder; if I go off the meds, I do and say things that cause me to lose friends, money, and sanity. Definitely not placebo. But who knows what you or I could achieve, given years of practice, through changes in diet, lifestyle, regular meditation and exercise, etc. It's entirely possible that our conditions can be overcome without meds, but the meds are necessary in the interim.
  16. Expat98
    Why Placebos Work Wonders - From Weight Loss To Fertility, New Legitimacy For 'Fake' Treatments

    by Shirley S. Wang, The Wall Street Journal
    January 3, 2012

    Say "placebo effect" and most people think of the boost they may get from a sugar pill simply because they believe it will work. But more and more research suggests there is more than a fleeting boost to be gained from placebos.

    A particular mind-set or belief about one's body or health may lead to improvements in disease symptoms as well as changes in appetite, brain chemicals and even vision, several recent studies have found, highlighting how fundamentally the mind and body are connected.

    It doesn't seem to matter whether people know they are getting a placebo and not a "real" treatment. One study demonstrated a strong placebo effect in subjects who were told they were getting a sugar pill with no active ingredient.

    Placebo treatments are sometimes used in some clinical practices. In a 2008 survey of nearly 700 internists and rheumatologists published in the British Medical Journal, about half said they prescribe placebos on a regular basis. The most popular were over-the-counter painkillers and vitamins. Very few physicians said they relied on sugar pills or saline injections. The American Medical Association says a placebo can't be given simply to soothe a difficult patient, and it can be used only if the patient is informed of and agrees to its use.

    Researchers want to know more about how the placebo effect works, and how to increase and decrease it. A more powerful, longer-lasting placebo effect might be helpful in treating health conditions related to weight and metabolism.

    Hotel-room attendants who were told they were getting a good workout at their jobs showed a significant decrease in weight, blood pressure and body fat after four weeks, in a study published in Psychological Science in 2007 and conducted by Alia Crum, a Yale graduate student, and Ellen Langer, a professor in the psychology department at Harvard. Employees who did the same work but weren't told about exercise showed no change in weight. Neither group reported changes in physical activity or diet.

    Another study, published last year in the journal Health Psychology, shows how mind-set can affect an individual's appetite and production of a gut peptide called ghrelin (GREL-in), which is involved in the feeling of satisfaction after eating. Ghrelin levels are supposed to rise when the body needs food and fall proportionally as calories are consumed, telling the brain the body is no longer hungry and doesn't need to search out more food.

    Yet the data show ghrelin levels depended on how many calories participants were told they were consuming, not how many they actually consumed. When told a milkshake they were about to drink had 620 calories and was "indulgent," the participants' ghrelin levels fell more—the brain perceived it was satisfied more quickly—than when they were told the shake had 120 calories and was "sensible."

    The results may offer a physiological explanation of why eating diet foods can feel so unsatisfying, says Ms. Crum, first author on the study. "That mind-set of dieting is telling the body you're not getting enough."

    Studies across medical conditions including depression, migraines and Parkinson's disease have found that supposedly inert treatments, like sugar pills, sham surgery and sham acupuncture, can yield striking effects. A 2001 study published in Science found that placebo was effective at improving Parkinson's disease symptoms at a magnitude similar to real medication. The placebo actually induced the brain to produce greater amounts of dopamine, the neurotransmitter known to be useful in treating the disease.

    At times, a weaker placebo effect might be desired. In trials of experimental drug treatments for dementia, depression and other cognitive or psychiatric conditions, where one patient group takes medication and the other takes a sugar pill, it can be difficult to demonstrate that the medicine works because the placebo effect is so strong.

    With depression, an estimated 30% to 45% of patients—or even more, in some studies—will respond to a placebo, according to a review published in December in Clinical Therapeutics. An additional 5% of patients were helped by an antidepressant in cases of mild depression, and an additional 16% in cases of severe depression. (The clinically meaningful cutoff for additional benefit was 11%.)

    Fertility rates have been found to improve in women getting a placebo, perhaps because they experience a decrease in stress. A recent randomized trial of women with polycystic ovarian syndrome found that 15%, or 5 of 33, got pregnant while taking placebo over a six-month period, compared with 22%, or 7 of 32, who got the drug—a statistically insignificant difference. Other studies have demonstrated pregnancy rates as high as 40% in placebo groups.

    Ted Kaptchuk, director of Harvard's Program in Placebo Studies and the Therapeutic Encounter, and colleagues demonstrated that deception isn't necessary for the placebo effect to work. Eighty patients with irritable bowel syndrome, a chronic gastrointestinal disorder, were assigned either a placebo or no treatment. Patients in the placebo group got pills described to them as being made with an inert substance and showing in studies to improve symptoms via "mind-body self-healing processes." Participants were told they didn't have to believe in the placebo effect but should take the pills anyway, Dr. Kaptchuk says. After three weeks, placebo-group patients reported feelings of relief, significant reduction in some symptoms and some improvement in quality of life.

    Why did the placebo work—even after patients were told they weren't getting real medicine? Expectations play a role, Dr. Kaptchuk says. Even more likely is that patients were conditioned to a positive environment, and the innovative approach and daily ritual of taking the pill created an openness to change, he says.

    Do placebos work on the actual condition, or on patients' perception of their symptoms? In a study published last year in the New England Journal of Medicine, Dr. Kaptchuk's team rotated 46 asthma patients through each of four types of treatment: no treatment at all, an albuterol inhaler, a placebo inhaler and sham acupuncture. As each participant got each treatment, researchers induced an asthma attack and measured the participant's lung function and perception of symptoms. The albuterol improved measured lung function compared with placebo. But the patients reported feeling just as good whether getting placebo or the active treatment.

    "Right now, I think evidence is that placebo changes not the underlying biology of an illness, but the way a person experiences or reacts to an illness," Dr. Kaptchuk says.

    Placebo can be more effective than the intended treatment. In a trial published in the journal Menopause in 2007, 103 women who had menopausal hot flashes got either five weeks of real acupuncture, or five weeks of sham acupuncture, where needles weren't placed in accepted therapeutic positions. A week after treatments ended, only some 60% of participants in both groups reported hot flashes—a robust immediate placebo effect. Seven weeks post-treatment, though, 55% of patients in the sham acupuncture group reported hot flashes, compared with 73% in the real acupuncture group.

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