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The Placebo Effect

arthwollipot said:
I believe Mike has spoken about the nocebo effect, but I don't recall specifically what he has said. As I understand it though, nocebo effects are a vastly different thing from the purported Powerful Placebo effect.
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The difference may be the powerful physiological effect of nocebo in some cases. Robert Bartholomew has mentioned the case of a young man who decided to kill himself by using pills he had because he participated in a study. After having swallowed the pills, he regretted his decision and was taken to the hospital where they measured his symptoms, one of which was very high blood pressure. The people conducting the study were contacted about the effects of the pills, and they informed the hospital that this particular patient was in the placebo group. After he was told, his blood pressure normalized in 15 minutes.

In Project Brazen's podcast series about the 'Havana syndrome', mass psychogenic illness (MPI) is dismissed as the cause because one of the victims, Karen Coats, has retinal bleeding, which isn't usually a symptom of MPI. However, it can be a symptom of hypertension.
 
Roger Ramjets said:
Not so fast.

The first example in the QED video showed a placebo response almost as powerful as the real treatment. It only 'disappeared' when an objective measurement was made. If this isn't done then the study has failed to collect the necessary data. But getting truly objective data can be difficult.

It would be a pity if an effective treatment was discarded for being 'no better than placebo' when the real failure was the study itself. Where a strong placebo effect is found it should be investigated to find the cause(s). You should not merely presume that the treatment was ineffective.
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If we are talking about drugs, I think you can rely on pharmaceutical companies not to give up on a new drug just because it doesn't seem to be better than placebos at first glance.
In the case of the asthma inhaler* study that you refer to, the lung capacity can be measured objectively, and it was being done as part of the study.

If you only listened to the the first part of the lecture, I recommend that you go back and listen to the other examples: peptic ulcer medication, the exercise effect of working as a cleaner and shoulder surgery. (These are the ones I remember.) There are many confounding factors to consider. In the shoulder study, for instance, they didn't seem to think that it was of any importance that physiotherapy was given to both the surgery and the sham surgery (placebo) group but not to the no-surgery group.


*I don't have asthma, but it seems like my health profile looks as if I'm predisposed to have it, so over the years I have been through the inhaler test for asthma three times. The first time was when I was diagnosed with grass and mugwort allergies. I didn't have any symptoms of asthma, but it was done to exclude the possibility. The next two times were when my doctor had trainees even though I told them that I didn't have asthma and had been tested. They almost seemed to be disappointed when the inhaler test showed that my (good) lung capacity was unaffected by asthma medication. :)
 
dann said:
If you only listened to the the first part of the lecture, I recommend that you go back and listen to the other examples: peptic ulcer medication, the exercise effect of working as a cleaner and shoulder surgery. (These are the ones I remember.) There are many confounding factors to consider. In the shoulder study, for instance, they didn't seem to think that it was of any importance that physiotherapy was given to both the surgery and the sham surgery (placebo) group but not to the no-surgery group.
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This last one, in fact, is the source of the wrong interpretation that since the treatment and the placebo arm gave the same results, the placebo was as good as the treatment. As opposed to the correct interpretation, which is that the treatment is no better than the placebo.
 
dann said:
After having swallowed the pills, he regretted his decision and was taken to the hospital where they measured his symptoms, one of which was very high blood pressure. The people conducting the study were contacted about the effects of the pills, and they informed the hospital that this particular patient was in the placebo group. After he was told, his blood pressure normalized in 15 minutes.
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I had a similar experience when staying in hospital overnight for observation a couple of years ago. The nurse made the mistake of letting me see the monitor. As the numbers went up I panicked and they went up even more until the alarms bells were literally ringing. Amazing biofeedback effect!

If only I could harness that effect in reverse I could stop taking these damned blood pressure pills.
 
I assume the nurse was able to calm you down again. Maybe she should have used a placebo monitor showing you that everything was fine. :)

In the book by Robert Baloh that I mentioned in post 196, he mentions how important the attitude of doctors are, but he stresses that it would be unethical to resort to 'alternative facts'.
I just got to Chapter 6. Psychosocial Mechanisms of Psychosomatic Symptoms:
Keywords Placebo - Nocebo - Beliefs - Expectations - Attentional system - Hyperventilation syndrome - Carbon dioxide - Environmental intolerance - Mass hysteria

When I got a Soberana plus shot in Cuba in October '22 along with two other Scandinavians, they measured our blood pressure before we got the shots and again before we were allowed to leave. 20 minutes after the shots, two of us were fine, but it was slightly elevated in the third, the youngest of us, so we waited another another 15 minutes, and it still wasn't good.

I suspected that it might be a case of 'peer pressure': That he was embarrassed by being the one who couldn't 'pass the exam', exacerbated by the two of us being older than him. I also think that it was a mistake to have all of us in the same room. When we had been measured before the shots, it happened in separate rooms, and he didn't have any problems then.
 
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dann said:
The difference may be the powerful physiological effect of nocebo in some cases. Robert Bartholomew has mentioned the case of a young man who decided to kill himself by using pills he had because he participated in a study. After having swallowed the pills, he regretted his decision and was taken to the hospital where they measured his symptoms, one of which was very high blood pressure. The people conducting the study were contacted about the effects of the pills, and they informed the hospital that this particular patient was in the placebo group. After he was told, his blood pressure normalized in 15 minutes.

In Project Brazen's podcast series about the 'Havana syndrome', mass psychogenic illness (MPI) is dismissed as the cause because one of the victims, Karen Coats, has retinal bleeding, which isn't usually a symptom of MPI. However, it can be a symptom of hypertension.
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And that takes us right back to the kind of thing that placebo is thought of as commonly. Which is apparently not the case. But in this case it turns out that it is. (Of course, this one's Placebo's dark other, Nocebo, but still. If the one can happen, if the one did actually happen; then it is not inconceivable that the other might also happen.)

This sort of thing leaves me a bit confused. On the one hand, basis this thread, it's become clear that Placebo's merely the placeholder term for all uncontrolled factors, and that it isn't the mind-drives-the-body nonsense idea that some put forward to support things like homeopathy. On the other hand, here's an instance of exactly that sort of thing happening, except in the opposite direction. What is one to actually believe, then?

...Unless, this report about how the Nocebo thing kicked in, is not as it appears? I don't know that that's the case, but I don't see any other way out of this ...conundrum?
 
I think that the difference is that anxiety (= nocebo effect) may lead to, e.g. depression or hypertension. We also know that hypertension isn't very healthy. It may cause retinal bleeding, for instance. (And blood pressure can be measured. It's not a question of merely reporting subjective symptoms.)
I suspect that the placebo effect, to the extent that it is more than a change in the way symptoms are reported, may be due to alleviating anxiety and thus depression, hypertension etc., i.e. a sugar pill against the nocebo effect.
 
arthwollipot said:
I don't know much about the nocebo effect, except the name.
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The nocebo effect
The nocebo effect is the opposite of the placebo effect. It describes a situation where a negative outcome occurs due to a belief that the intervention will cause harm. It is a sometimes forgotten phenomenon in the world of medicine safety. The term nocebo comes from the Latin ‘to harm’.

For adverse reactions to medicines, nocebo implies that patients are more likely to experience an adverse effect if they expect or are worried about the adverse effect. The adverse effects may be physically experienced by the patient and are often clinically diagnosable. An example of the nocebo effect is the severe adverse effects experienced by patients taking a placebo during a clinical trial.
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It is a very real thing that anxiety and stress can cause spikes in blood pressure:
Anxiety.
Depression.
Being cut off from friends and family.
There's no proof that these conditions are directly linked to high blood pressure. But the hormones the body makes when under emotional stress might damage arteries. The artery damage might lead to heart disease. And symptoms of depression and anxiety might cause some people to forget to take medicines to control high blood pressure or other heart conditions.
Stress and high blood pressure: What's the connection? (Mayo Clinic)
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Anxiety doesn't cause long-term high blood pressure (hypertension). But episodes of anxiety can cause dramatic, temporary spikes in blood pressure.
If those temporary spikes occur frequently, such as every day, they can cause damage to blood vessels, the heart and kidneys, as can chronic high blood pressure. In addition, people who are anxious or stressed are more likely to engage in unhealthy habits that can raise blood pressure, such as:
Smoking
Drinking alcoholic beverages
Overeating
Anxiety: A cause of high blood pressure? (Mayo Clinic)
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Daily briefing: ‘Nocebo’ effect underlies most COVID vaccine side effects (Nature, Jan 19, 2022) [/quote]
And then there's the effect of anxiety that it may turn people into antivaxxers, but that is no longer the nocebo effect unless it is caused by experiencing the nocebo effect in previous vaccinations.
 
Well, yeah, there's similar claims about the placebo effect too. I don't know of anyone who has gone the full Mike Hall on nocebo.
 
I already mentioned Robert Baloh's book Medically Unexplained Symptoms: A Brain-Centered Approach.
In the last chapter, he writes:
For centuries, spiritual and medical healers have taken advantage of the most powerful treatment of all - reassurance. It works regardless of the cause of symptoms, but it is particularly effective with psychosomatic symptoms because fear and anxiety are often at the heart of the problem.
(...)
Stress is the major driving force for the production of psychosomatic symptoms and fear, anxiety and depression are natural reactions to chronic stress.
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If stress-induced fear, anxiety and depression are at the heart of the problem, I think that it kind of confirms my idea that nocebo is the real phenomenon, which can cause actual harm, whereas placebo isn't more than a kind of 'anti-nocebo'. A placebo may relieve your pain and make you feel better, which isn't bad and should be appreciated in and of itself, but it doesn't mend your broken leg or cure your cancer.
Nocebo, however, has actual physiological consequences - the physiological consequences of anxiety, for instance hypertension.

Baloh ends the introduction to the last chapter with:
Lifestyle changes, mindfulness and cognitive therapies are useful for treating all types of psychosomatic (!) symptoms and overall are currently the most effective treatments.
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arthwollipot said:
I believe Mike has spoken about the nocebo effect, but I don't recall specifically what he has said. As I understand it though, nocebo effects are a vastly different thing from the purported Powerful Placebo effect.
Click to expand...


The placebo and nocebo effect are the same thing: a form of confirmation bias. There is no good evidence that the "powerful placebo" exists.
 
In case anybody wants to hear a more complicated version of the story about placebos:
RFK Jr. resurrects an old antivax half-truth about “saline placebos” in randomized controlled trials of vaccines (Science-Based Medicine, July 3, 2023):

In a placebo-controlled trial, subjects are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug. The treatments may be titrated to effect or tolerance, or may be given at one or more fixed doses. Such trials are almost always double-blind. The name of the control suggests that its purpose is to control for “placebo” effect (improvement in a subject resulting from thinking that he or she is taking a drug), but that is not its only or major benefit. Rather, the placebo control design, by allowing blinding and randomization and including a group that receives an inert treatment, controls for all potential influences on the actual or apparent course of the disease other than those arising from the pharmacologic action of the test drug. These influences include spontaneous change (natural history of the disease and regression to the mean), subject or investigator expectations, the effect of being in a trial, use of other therapy, and subjective elements of diagnosis or assessment. Placebo-controlled trials seek to show a difference between treatments when they are studying effectiveness, but may also seek to show lack of difference (of specified size) in evaluating a safety measurement. In that case, the question of whether the trial could have shown such a difference if there had been one is critical (see section 1.5).
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This is actually a quotation from another article, and there is much, much more. It's a rather long but extremely interesting article. It mentions several kinds of controls where placebos are used in different ways - or not at all:
(i) Placebo concurrent control.
(ii) Dose-comparison concurrent control.
(iii) No treatment concurrent control.
(iv) Active treatment concurrent control.
(v) Historical control.

I wasn't aware that placebo control groups sometimes receive actual treatment:
The use of a placebo control group does not imply that the control group is untreated. In many placebo-controlled trials, the new treatment and placebo are each added to a common standard therapy (so called add-on studies, see section 2.1.5.2.1).
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The power of placebo-controls has little to do with the placebo-effect

“I’m addicted to placebos. I could quit, but it wouldn’t matter.” – Steven Wright

Placebo controls are a mainstay of clinical research in medicine. They are one of the gold standard features of the iconic “double-blind, randomised, placebo-controlled clinical trial.” This is surely an affirmation of the potency of the mighty placebo effect, right? No really!

Even if placebo effects are a myth, placebo controls would remain a powerful tool to improve the quality of clinical trials.
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Steve Novella discusses acupuncturist Ted Kaptchuk, who for some reason is a director of placebo studies at Harvard:

Placebo Effect Revisited

In a recent editorial for The New York Times, researcher Ted J. Kaptchuk, who directs placebo studies at Harvard, gives his summary of the current state of research (much of it his own) into placebo effects. While much of what he says is true, or at least uncontroversial, in my opinion he shoehorns the facts into his preferred narrative – a popular narrative that can be counterproductive and feeds into unscientific medical treatments...
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And I note that once again it is the New York Times that is promoting pseudoscientific bull. Whatever good reputation that paper once had, it is fast being eroded.
 
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