Q. Do placebos work? How and when are they effective? What can our current neuroscience tell us about them?
G. A critical element in contemporary medicine is evaluating how successful pharmaceuticals are. They are judged against what would seem an easy target - "doing nothing", i.e. giving someone an inactive substance or procedure in place of the real one they are told they are getting, or placebos. However, recent major pharmaceutical developments, some w/huge amounts of research behind them, were scrapped when their results were no better than placebos.
Class action lawsuits were filed last month against Pfizer for possessing research demonstrating that the antidepressant Zoloft was no more effective than a placebo and "deliberately withholding this information from consumers and then advertising this drug as very effective". Merck had a similar problem w/another "breakthrough" antidepressant, MK-869. Although a great deal of research had been conducted, MK-869 could not beat the placebos and was abandoned.
Similarly, a new gene therapy for Parkinson's disease was abruptly withdrawn after unexpectedly failing against a placebo. Eli Lilly broke off testing a much-touted new drug for schizophrenia when the placebo unexpectedly matched it. Osiris Therapeutics, a stem-cell startup, suspended trials of its pill for Crohn's disease, an intestinal ailment, when it failed against placebos.
How were these powerful placebos discovered? Although they have been around, and have been controversial, for a long time, modern work is traced to World War II on the beaches of southern Italy. A nurse assisting the anesthetist was running out of morphine for pain for wounded soldiers. She told one soldier that he was receiving morphine and instead gave him what she had, which was saline solution (salt water). To everyone's surprise, the soldier's agony was relieved and he did not go into shock which would have been life-threatening.
The anesthetist, Henry K. Beecher, returned to Harvard after the war and published the landmark paper on the subject, "The Powerful Placebo" in 1955. Beecher's estimate, based on a study of over 1000 patients in 15 clinical trials, was that 35% of any group responded to a placebo. However, not until 1968 did the FDA formally begin using placebos in standard clinical trials to ensure that drugs really worked as advertised.
Currently, another Harvard folk, Ted Kaptchuk, director of the newly launched "Program in Placebo Studies" is studying placebos w/our latest technology. Interestingly, after his undergraduate degree, Kaptchuk went to China to get a doctor of Oriental medicine degree (OMD) and studied acupuncture. After 15 years of work, he concluded that the curative effects of his practice were not due to the needles themselves and set out to understand why.
Subsequently, Kaptchuk and others found some flaws in Beecher's work, e.g. there was no accounting for folk who got better "all by themselves" and different ailments responded differently to different placebos. Placebo shots worked best for pain relief, but placebo pills worked better for insomnia.
A major issue was how "improvement" was measured. If medical, "objective" measurements like blood pressure were used, placebos did not appear to work. But if researchers measured how patients "felt", placebos were effective especially for pain and nausea.
Another Harvard folk, Irving Kirsch, in 2002 confirmed that placebos are most powerful when improvement is "subjective". In research on six popular antidepressants, Kirsch, et al. discovered that 82% (yes 82%) of the improvement in mood measured by standard questionnaires could be duplicated w/a placebo. Kirsch followed this in 2008 w/work that demonstrated that antidepressants only work significantly better than placebos in the most severe cases of extreme depression. No surprise, there is much controversy over these results.
More recent work has looked at what role cognitive neuroscience can play in understanding placebos. Tor Wager and his colleagues @ the Univ. of Colorado @ Boulder were able to separate w/MRI what regions were involved in the placebo effect.
Subjects were given a "get ready" sign before receiving a painful stimulus or intense heat and before receiving a placebo cream. Wager found that the prefrontal cortex, the "executive center" of the brain, tells the midbrain centers like the amygdala to release endogenous opioids in expectation of a reprieve from the pain which will be felt.
Subsequent work (2011) was published in the Journal of Neuroscience by Wager, et al., "Predicting individual differences in Placebo Analgesia: Contributions of Brain Activity During Anticipating and Pain Experience". This demonstrated that centers associated w/emotions such as the insula, orbitofrontal cortex and amygdala were activated to generate a strong placebo effect. Wager calls this "endogeneous regulation", or the ability for humans to "reinterpret their situation". He also adds that during a placebo response "our brain is likely doing a lot of the work w/o our real conscious input or even in spite of our conscious desires."
Wager's (2012) work w/Buhle and others @ Columbia, "Distraction and Placebo: Two Separate Route to Pain Control" gives some advice on how to deal with pain. Distracting subjects from experimentally-induced pain did not help them feel better. Paying attention to the pain by ranking its intensity provided greater relief. This is in line w/"acceptance" and "relaxation response" therapies in which folk who surrender to their pain are better able to tolerate it.
Pain relief approaches, placebo and pharmaceutical, were separated neuroscientifically in recent experiments. Pain relief occurred for injections of both the opioid remifentanil and the "expectation of pain relief" placebo (saline solution). The placebo reduced pain quickly by increasing the activity in the prefrontal cortex and reducing activity in the emotional areas. The opioid worked but took longer to reach its peak. This has led the way to a combined approach with higher efficacy.
Kaptchuk and his folk published work on irritable bowel syndrome (IBS) treated with a) either his specialty, acupuncture, or a waiting list and b) different levels of interaction w/the physician. Waiting list folk had a 28% improvement. "No conversation" doctor/patient interactions w/acupuncture gave a 44% improvement. "Heavy attention" doctor/patient interaction w/acupuncture gave a 62% improvement.
As it turns out, even if the IBS patients are told they are going to receive "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS...", they feel better overall w/less severe symptoms than folk receiving no treatments. This work is covered in Kaptchuk, Kirsch, et al. in "Placebos Without Deception..." in Plos One in 2010. Placebos don't require "deception".
In summary, paying attention to your pain, (and thoughts about pain, i.e. suffering) is more powerful than ignoring it. The "mental game" is really important for much subjectively-determined discomfort, depression, nausea and pain; drugs are most useful for acute situations. Oh, and if you break your leg, see a doctor, hopefully one who will communicate w/you.
BTW, there are several youTube videos up now on "Do It Yourself" (DIY) non-dual awakening; a) "Nondual awakening meditation - Where am I?", b) "Using simple chants for nondual awakening", c) "Using yoga posture flows for nondual awakening, and d) "What types and patterns of thoughts do you have? What can be done w/them?". Coupled with the three blogposts on Dialogues w/Dominic identified with "DIY" in their title, these should be useful resources for your personal practices.
G. A critical element in contemporary medicine is evaluating how successful pharmaceuticals are. They are judged against what would seem an easy target - "doing nothing", i.e. giving someone an inactive substance or procedure in place of the real one they are told they are getting, or placebos. However, recent major pharmaceutical developments, some w/huge amounts of research behind them, were scrapped when their results were no better than placebos.
Class action lawsuits were filed last month against Pfizer for possessing research demonstrating that the antidepressant Zoloft was no more effective than a placebo and "deliberately withholding this information from consumers and then advertising this drug as very effective". Merck had a similar problem w/another "breakthrough" antidepressant, MK-869. Although a great deal of research had been conducted, MK-869 could not beat the placebos and was abandoned.
Similarly, a new gene therapy for Parkinson's disease was abruptly withdrawn after unexpectedly failing against a placebo. Eli Lilly broke off testing a much-touted new drug for schizophrenia when the placebo unexpectedly matched it. Osiris Therapeutics, a stem-cell startup, suspended trials of its pill for Crohn's disease, an intestinal ailment, when it failed against placebos.
 |
| R. Hogan Discoverer of Modern Placebos |
How were these powerful placebos discovered? Although they have been around, and have been controversial, for a long time, modern work is traced to World War II on the beaches of southern Italy. A nurse assisting the anesthetist was running out of morphine for pain for wounded soldiers. She told one soldier that he was receiving morphine and instead gave him what she had, which was saline solution (salt water). To everyone's surprise, the soldier's agony was relieved and he did not go into shock which would have been life-threatening.
 |
| Henry K. Beecher Harvard University |
The anesthetist, Henry K. Beecher, returned to Harvard after the war and published the landmark paper on the subject, "The Powerful Placebo" in 1955. Beecher's estimate, based on a study of over 1000 patients in 15 clinical trials, was that 35% of any group responded to a placebo. However, not until 1968 did the FDA formally begin using placebos in standard clinical trials to ensure that drugs really worked as advertised.
Currently, another Harvard folk, Ted Kaptchuk, director of the newly launched "Program in Placebo Studies" is studying placebos w/our latest technology. Interestingly, after his undergraduate degree, Kaptchuk went to China to get a doctor of Oriental medicine degree (OMD) and studied acupuncture. After 15 years of work, he concluded that the curative effects of his practice were not due to the needles themselves and set out to understand why.
 |
| Ted Kaptchuk Harvard University |
Subsequently, Kaptchuk and others found some flaws in Beecher's work, e.g. there was no accounting for folk who got better "all by themselves" and different ailments responded differently to different placebos. Placebo shots worked best for pain relief, but placebo pills worked better for insomnia.
A major issue was how "improvement" was measured. If medical, "objective" measurements like blood pressure were used, placebos did not appear to work. But if researchers measured how patients "felt", placebos were effective especially for pain and nausea.
Another Harvard folk, Irving Kirsch, in 2002 confirmed that placebos are most powerful when improvement is "subjective". In research on six popular antidepressants, Kirsch, et al. discovered that 82% (yes 82%) of the improvement in mood measured by standard questionnaires could be duplicated w/a placebo. Kirsch followed this in 2008 w/work that demonstrated that antidepressants only work significantly better than placebos in the most severe cases of extreme depression. No surprise, there is much controversy over these results.
 |
| Tor Wager Univ of CO @ Boulder |
Subjects were given a "get ready" sign before receiving a painful stimulus or intense heat and before receiving a placebo cream. Wager found that the prefrontal cortex, the "executive center" of the brain, tells the midbrain centers like the amygdala to release endogenous opioids in expectation of a reprieve from the pain which will be felt.
 |
| Amygdala |
 |
| Orbitofrontal Cortex |
Wager's (2012) work w/Buhle and others @ Columbia, "Distraction and Placebo: Two Separate Route to Pain Control" gives some advice on how to deal with pain. Distracting subjects from experimentally-induced pain did not help them feel better. Paying attention to the pain by ranking its intensity provided greater relief. This is in line w/"acceptance" and "relaxation response" therapies in which folk who surrender to their pain are better able to tolerate it.
Pain relief approaches, placebo and pharmaceutical, were separated neuroscientifically in recent experiments. Pain relief occurred for injections of both the opioid remifentanil and the "expectation of pain relief" placebo (saline solution). The placebo reduced pain quickly by increasing the activity in the prefrontal cortex and reducing activity in the emotional areas. The opioid worked but took longer to reach its peak. This has led the way to a combined approach with higher efficacy.
 |
| Irving Kirsch Harvard University |
As it turns out, even if the IBS patients are told they are going to receive "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS...", they feel better overall w/less severe symptoms than folk receiving no treatments. This work is covered in Kaptchuk, Kirsch, et al. in "Placebos Without Deception..." in Plos One in 2010. Placebos don't require "deception".
In summary, paying attention to your pain, (and thoughts about pain, i.e. suffering) is more powerful than ignoring it. The "mental game" is really important for much subjectively-determined discomfort, depression, nausea and pain; drugs are most useful for acute situations. Oh, and if you break your leg, see a doctor, hopefully one who will communicate w/you.
BTW, there are several youTube videos up now on "Do It Yourself" (DIY) non-dual awakening; a) "Nondual awakening meditation - Where am I?", b) "Using simple chants for nondual awakening", c) "Using yoga posture flows for nondual awakening, and d) "What types and patterns of thoughts do you have? What can be done w/them?". Coupled with the three blogposts on Dialogues w/Dominic identified with "DIY" in their title, these should be useful resources for your personal practices.
No comments:
Post a Comment