Placebo effect discussion thread

In a treatment using some form of placebo for, say, a sore shoulder, how long would the treating doctor or therapist expect the placebo effect to last before pain returns? If it returns? Are we talking hours? days? weeks? months? years? permanently?

 

Something like that would be one possibility. Of course the information would not be the only causal factor. There would need to be some aberrant neurological state of the person being informed.

 

What about the children to parents with Huntington’s Disease that experience symptoms before testing, but turns out to be negative? Would they have to have an aberrant neurological state? What does an aberrant neurological state mean?

 

Fluge and Mella are currently doing a small study on Daratumumab:
https://www.s4me.info/threads/pilot-study-in-norway-daratumumab-in-me-cfs.28098/

 

The same possibly has occurred to me, although it would be surprising to me if such people did not respond in trials of psycho-behavioural interventions. Presumably, the motivation for many people who volunteer for trials is because they believe the invention may help them. But perhaps it could be the degree of belief in the intervention that matters.

If such a hypothetical subgroup existed, the theory would face the same problems of falsifiability as the CBT/GET models. And it would be hard to design trials that did not breach the sort ethical and methodological standards that the BPS enthusiasts have been happy to ignore.

It has occurred to me before that if that if hypochondriacs exist it would be surprising if at least some did not convince themselves that they have ME/CFS. Similarly, it would be surprising if malingers did not try to convince others that they have ME/CFS.

 

Wouldn’t a hypochondriac be very interested in participating in treatment trials? I’m assuming they do not want to be sick at all - so they would be willing to test anything to get better.

Given how few people that respond to GET and CBT in the trials, it would indicate that there are quite few hypochondriacs among the participants.

Another issue is how unreliable self-diagnosis is. We’ve seen a few studies that show at least half or the self-reported ME/CFS patients do not actually fulfil the diagnostic criteira.

 

If the subgroup that I describe above existed then we would not expect those patients to respond to CBT and GET, only to biomedical interventions that they were sufficiently convinced would help them.

 

I don't think it would be surprising. The psycho-behavioural approach denies the existence of a 'disease' beyond one's rumination over being ill. Physical interventions and even LP reify that 'disease' and legitimise the hypochondriasis state. Moreover, you cannot apply rational argument to this reliably, even my suggestion. We really don't know how brains work, even normally and certainly not when they are not working normally. I come back to the idea that we should not be too surprised if some people who get a diagnosis of ME/CFS have a primarily 'neuropsychiatric' disorder, like my wife and her psychosis. The real problem with the psychological medicine people is not so much that we should not consider that but the

 

I think I understand your point but I would be interested to know how this sentence ends.

 

Ah, a word-eating bug!

The real problem with the psychological medicine people is not so much that we should not consider that but the fact that they have no idea what they are doing because they think they have a way of understanding that is in fact folklore-based garbage.

 

What is the reasoning or argument behind this? Why should we not be surprised?

 

Because medical conditions are often stranger than we have considered might be the first answer.

Another thing would be that my wife's illness included all sorts of things that also occur in people diagnosed with ME/CFS, including an inability to eat or drink.

In mechanistic terms, in the paper a number of us published in Fatigue in 2016, we argued that ME/CFS seems likely to involve either immune or central nervous systems or both and in symptomatic terms it must involve CNS to mediate sensitivity to light. That may not tell us much in practice but these are the two systems complicated enough to produce a fluctuating illness like ME/CFS on the basis of some acquired error of control.

We tend to focus on the immune system but people are also interested in potential brain changes. Brain changes are neuropsychiatric. By which term I mean generating problems with thinking or perception that are secondary to some physical change in the brain tissue. But that change in the brain may make it susceptible to thoughts including beliefs that present in a way that mimics something else. My wife's psychosis mimicked a bowel obstruction, which she believed she had, regardless of any rational argument.

There are people who are quite sure they have lupus or rheumatoid arthritis or multiple sclerosis and have relevant symptoms but do not have these conditions. They are not rare. As I think Robert said, if there are 'hypochondriacs' then ME/CFS is something we might expect them to believe they have.

It may be unsettling but I don't think it should worry us unduly in the quest for the mechanism of ME/CFS.

A comment I remember Jo Begent making when discussing possible rituximab trials in 2014 has stuck in my mind. I am not saying she was right or wrong but I thought there might be something to it. She said that some patients (with ME/CFS) clearly had a physical problem. Others seemed clearly to have a psychiatric problem. The difficulty was knowing how to distinguish the bulk of patients where it was not possible to absolutely sure. And note that 'psychiatric' did not necessarily mean not physical here. I think she meant neuropsychiatric.

 

For the sake of the argument, let’s assume this is correct. I’m not comfortable with it yet and I’m not sure I completely understand it either.

Would you expect a neuropsychiatric ME/CFS patient to any biological findings (i.e. deviations) that are similar to those with physical ME/CFS?

 

They might do. If ME/CFS is abnormal signalling between brain and immune system it might be either the immune system or the brain that starts off at fault but the abnormal interaction might show up as the same. At the moment we don't have any findings to test.

 

we don't quote these classics enough as coercion and social pressure is used to an extreme extent in wangling 'results' from CFS people

- although I guess in part since some of the old psych experiments ended up being shown to have been dodgy for various reasons and I guess sometimes it is hard to want to rely on something just in case

 

Natelson ran a couple of placebo phase-in trials (of phenelzine and selegiline) in broadly defined CFS cohorts in the 1990s - the phase-in design in order to assess the magnitude of the placebo effect - and didn't find evidence of an unusually high placebo response as would be expected in illnesses associated with high levels of suggestibility.

I too think that even if a subgroup is "neuropsychiatric" that the biological underpinnings will be discovered in time. At the moment the neuropsychiatric field seems to be making new progress with some long-intractable problems, e.g. the developments in the study of schizophrenia. Last October a novel medication combination was approved in the US for schizophrenia that doesn't target D2 at all (one of the two drugs is an M1 & M4 agonist, the other a pan-mAChR antagonist); GWASes have also pointed to glutamatergic involvement - it seems there are multiple pathways which can lead to a symptom cluster that looks like one illness. For those interested:

"Revolutionary drug for schizophrenia wins US approval" (Nature, 2024)
"New treatments are rewriting our understanding of schizophrenia" (Scientific American, 2025)

 

https://www.s4me.info/threads/bbc-t...s-significant-results.6003/page-3#post-109929

 

Interesting. From the Scientific American article:

“At Oxford, Kabir, psychiatry professor Belinda Lennox and their colleagues are currently conducting a clinical trial to examine whether rituximab, an antibody used to treat arthritis and other autoimmune disorders, can effectively treat psychosis in people who have detectable neuronal autoantibodies in their blood.”​

 

Found this thread: https://www.s4me.info/threads/call-...l-after-evidence-of-autoimmune-trigger.33289/

 

Neurologists have been treating neuronal antibody-positive psychosis with rituximab for about a decade now. Not sure if this is something new. Probably not very relevant to most schizophrenia but who knows?