Placebo effect discussion thread

[Yann04]

That might not be at all surprising. Wikipedia says:
In accordance with its partial agonism, although naltrexone is described as a pure opioid receptor antagonist, it has shown some evidence of weak opioid effects in clinical and preclinical studies.[6]

It is a painkiller!

Yep. I agree with Jonathan that while there are myriad things that help with symptoms, it is important to note that it’s very likely that there is absolutely nothing (currently) that helps with the disease as a whole, even in just a single person.

 

[Trish]

I think placebo is potentially dangerous when trying to manage the reality of ME because it can prompt suppression and masking of significant symptoms leading to a failure to manage ME PEM and thereby cause crash and relapse.

I think your distressing story of the years you spent immersed in harmful quackery and the years it took to recover from the harm is really important.
I went on a similar journey into quack land but I'd already been diagnosed with ME, and although I don't think I heard the term PEM back in the early 1990's, my scepticism saved me from deep harm. Just a few crashes I could have done without.

A nice lady gave me copy of Louise Haye's "you Can Heal Your Life" so I gave NLP a go, which changed one's inner world for about 5 mins.

I was recommended that book by an aromatherapist who told me I wasn't getting better because I didn't want to. Fortunately by then I was starting to know better, and it just made me angry. i can't remember whether I actually bought the book. If I did it went in the bin.

 

[boolybooly]

Do you think I should write about it @Trish ? Maybe I will blog it one day just for my own satisfaction. Hardly anyone ever reads my stuff though, I am not sure I would be doing the world a service.

I was recommended that book by an aromatherapist who told me I wasn't getting better because I didn't want to. Fortunately by then I was starting to know better, and it just made me angry. i can't remember whether I actually bought the book. If I did it went in the bin.

Yes I think that is what the nice lady was trying to say but of course she was wrong. Shows how commonplace it is for people to see others' problems as related to character, which is the folly of the BPS perspective. My problem was of my making in a corporeal sense but not because I wanted it that way.

My body is the result of my genes and genes don't have desire, life plays genetic roulette and my roll was happenstance. Affirmations cannot change genetics. I think she was trying to give me what she hoped would help her, which is kind in a way, though misguided and again is what BPS does. She was in fact trying to extricate herself from a difficult, abusive sounding relationship but failing. Even there genetics plays its part. How fragile we are.

The trick of blaming those seeking help or solace for their pain was becoming quite popular around then. Though rudely insensitive, unsympathetic and offensive, that very fact means it has a shock effect which might cause some people to think again about their own responsibility for their situation and their options for changing it, such as walking away! I remember there was a touring self help show from the USA called The Forum who made a living out of it by staying on the move and finding new audiences to upset.

I suppose some people found this cruelty helpful or at least thought it would be helpful to others and it seemed to spread as a meme quite successfully in such circles. The "professional" therapist I went to see and I use that description loosely was far more enveigling but her advice was the same. Of course it echoes the truth of the muse, that we are all alone in a universe of perceptions we create subjectively. So it can be an effective power play over those who have not been there so to speak and are still children at heart but it is not actually helpful if you have faced the truth and have visited them seeking knowledge about a blight like ME because it provides none, just tells you what you know already.

I would prefer it if people just threw their hands up and admit they have no clue.

 

[Trish]

Do you think I should write about it @Trish ? Maybe I will blog it one day just for my own satisfaction. Hardly anyone ever reads my stuff though, I am not sure I would be doing the world a service.

Maybe one day if you feel like it you could start a thread here to describe your experiences as a warning to others, or write an article and see if you could get it shared somewhere. I'm no good at suggesting where.

I would prefer it if people just threw their hands up and admit they have no clue.

So very true.

 

[Hutan]

On the extent of placebo response the evidence seems rather mixed

I remember a BPS proponent, White or Sharpe?, said the people with CFS have a low placebo response. Perhaps that was why they needed to jazz up the treatments with newsletters saying how good they were.

I think the strength of the placebo effect depends on the strength of your belief that the treatment has a real biological effect.

Perhaps that was the problem with the BPS treatments - too many people didn't find the sell very compelling. I guess those BPS guys are not nearly on the same level as Fluge when it comes to generating hope.

I find a six-month placebo effect a very weird concept in ME/CFS, if it's merely based on expectation. If a PwME suddenly feels better without any change in their biology, I don't see how they can possibly become and remain more active - as they would, if they felt better - without having a massive crash within days or, at most, a very few weeks. We all live up to our energy envelopes because we're so heavily constrained and are desperate to be more active. This just seems a very strange scenario.

I can certainly see someone reporting that they feel better for six months. It's hard to think they could actually increase activity and sustain it for six months though. How was improvement measured in the early and later Rituximab trials? It's the sort of thing where it would be interesting to poke into that a bit more, interview the participants.

 

[Sean]

From what I can tell, the placebo effect is very much overstated in popular culture. It only has decent evidence behind it for nausea and pain, both of which are subjective outcomes.

IIRC, for pain it is not clear as the effect sizes are all over the place.

Also is not clear if it is an actual placebo effect taking place, or is a whole other bunch of methodological confounders that are not being properly controlled for, and are all just being placed in the placebo basket.

It is a complete mess, and the psychosomatic fans are in no hurry to clear it up.

 

[Sasha]

If I wanted to engineer a massive placebo effect for myself, how would I do it?

Book an appointment with Dr Oystein Fluge. He is the placebo incarnate. And it is not his fault because he is just very committed, very compassionate, very modest, very keen to get the science right and an overall loveable guy. And I think that caused him some problems but he and Olav Mella did things right and picked their way through all the confounders with huge skill.

On another thread, we were discussing a guy who might be a 'Rosseta stone' ME/CFS patient:

There was a pwME on reddit who was going through multiple multi-year cycles of ME/CFS with proper PEM etc and being completely normal, asymptomatic and able to train at the gym. I encouraged him to contact his nearest US researchers (not sure which state) to get baseline now and see what changes if he does revert to ME/CFS at some time. He was surprised that this wouldn't have been a common thing already evaluated, but I responded that there's an outside chance he could be an ME Rosetta stone.

Seriously, I would chip in good money for this guy not just to get baseline data but to be regularly and frequently monitored to catch him when the switch flips.

There are Rosetta Stone patients sometimes, such as people immune to HIV, that have allowed science to make great strides...

Such patients may be hard to find, and hard to catch at the moment they flip, but what if Dr Fluge is Rosetta-stone-producing doctor? What if he's such a brilliant generator of powerful placebo effects that he triggers real remissions (because I still don't find those 6-month rituximab remissions plausible as self-delusion)?

Could we get him to run a new clinical trial of a therapy that he genuinely thinks could be a goer, in the hope that we can catch the switch flipping in some of his patients?

@Jonathan Edwards

 

[Sasha]

I can certainly see someone reporting that they feel better for six months. It's hard to think they could actually increase activity and sustain it for six months though. How was improvement measured in the early and later Rituximab trials? It's the sort of thing where it would be interesting to poke into that a bit more, interview the participants.

Feeling better, yes, but didn't they report being in remission? I interpreted that as meaning they felt as though they had recovered.

It would be interesting to have more detail about this.

 

[Jonathan Edwards]

I remember a BPS proponent, White or Sharpe?, said the people with CFS have a low placebo response.

It was White and Knoop and in the same paper they said that CBT worked through the placebo response!

 

[Jonathan Edwards]

I can certainly see someone reporting that they feel better for six months. It's hard to think they could actually increase activity and sustain it for six months though.

I think in all these discussions we need to be open to the possibility that a diagnosis ME/CFS is applicable to two or more very different sorts of illness - that just tick the same boxes.

 

[Sasha]

I think in all these discussions we need to be open to the possibility that a diagnosis ME/CFS is applicable to two or more very different sorts of illness - that just tick the same boxes.

Quite a lot of us might be in those subcategories, though. I remember it being said that ME/CFS might be a dozen different illnesses. Whoever those people are who are going into 6-month remissions, if they were given an ME/CFS diagnosis, they're presumably in an ME/CFS subcategory and need investigating.

 

[Mij]

Use of placebo controls in evaluation of surgery

A fascinating landmark study of placebo surgery for knee osteoarthritis

 

[rvallee]

I remember a BPS proponent, White or Sharpe?, said the people with CFS have a low placebo response. Perhaps that was why they needed to jazz up the treatments with newsletters saying how good they were.

I also remember Wessely replying to someone commenting on this about PACE that "the placebo is one one of the most powerful interventions we have". Although he would likely say something else to different audiences, then and now.

Which is a comically inept thing to admit: the best we can do is to amplify the very noise that serious researchers try to eliminate. Basically: our very best is the null comparator. We are NULL.

 

[Jonathan Edwards]

Quite a lot of us might be in those subcategories, though. I remember it being said that ME/CFS might be a dozen different illnesses. Whoever those people are who are going into 6-month remissions, if they were given an ME/CFS diagnosis, they're presumably in an ME/CFS subcategory and need investigating.

What would you investigate, @Sasha? We haven't found anything to distinguish people with ME/CFS from healthy controls much so where would you start separating two groups both with normal tests? If a significant proportion of people with ME/CFS fell into a group that did have abnormal tests we should have seen that.

I rather doubt that many people on S4ME fall into a group that can suddenly become active for six months, relapse to order and then do it again. But it looks as if some can and I can think of one or two high profile ME/CFS advocates who seem to go through these phases.

If you can think of a way to gather information that would be great but I haven't been able to think of one so far.

 

[boolybooly]

Use of placebo controls in evaluation of surgery

A fascinating landmark study of placebo surgery for knee osteoarthritis

The appropriate context being Milgram and a perspective on obedience and conformism, because people will say what they believe they are expected to say.

Which is why empirical measurement data is a good basis for science and self reporting data is not.

It is comparable to the problem of anthropomorphism in zoology. You have to rule out cognitive bias in the experimental method. Anything less is not credible.

 

[Maat]

A nice lady gave me copy of Louise Haye's "you Can Heal Your Life" so I gave NLP a go, which changed one's inner world for about 5 mins.

Snap! My copy ended up in a charity shop.

 

[Sasha]

What would you investigate, @Sasha? We haven't found anything to distinguish people with ME/CFS from healthy controls much so where would you start separating two groups both with normal tests? If a significant proportion of people with ME/CFS fell into a group that did have abnormal tests we should have seen that.

I rather doubt that many people on S4ME fall into a group that can suddenly become active for six months, relapse to order and then do it again. But it looks as if some can and I can think of one or two high profile ME/CFS advocates who seem to go through these phases.

If you can think of a way to gather information that would be great but I haven't been able to think of one so far.

I don't think we could separate those two groups of PwME in advance. The ideal would be to get people we know go through these phases, or who are likely too (like Dr Fluge's patients!).

 

[DigitalDrifter]

Jockenhöfer, F., Knust, C., Benson, S., Schedlowski, M. and Dissemond, J. (2020), Influence of placebo effects upon quality of life and wound healing in patients with chronic venous leg ulcers. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 18: 103-109.

It has been shown that the mere expectation of a study subject to receive (or to no longer receive) a strong pain medication significantly enhances (or neutralizes) the analgesic effects of the opiate given.

Citation needed.

 

[Sean]

I would prefer it if people just threw their hands up and admit they have no clue.

Which is a comically inept thing to admit: the best we can do is to amplify the very noise that serious researchers try to eliminate.

What they said.

 

[Robert 1973]

Sorry, I'm late to this thread.

I think in all these discussions we need to be open to the possibility that a diagnosis ME/CFS is applicable to two or more very different sorts of illness - that just tick the same boxes.

Do you mean that there may be a subgroup of people with an ME/CFS diagnosis whose symptoms develop as a consequence of information they acquire about the illness (ie their beliefs), who may respond positively to a 'dummy' biomedical intervention that they believe will help them, but not to a psycho-behavioural intervention that they do not believe in? Or am I misunderstanding you?