Phoenix Rising: The Gift That Keeps on Giving All Year Long
This holiday season Jody Smith turns her eyes to the people of Phoenix Rising and gives thanks for you all ...
Discuss the article on the Forums.

Diseases the placebo effect works for, and ones it doesn't work for (it's to do with dopamine)

Discussion in 'Other Health News and Research' started by Hip, Dec 12, 2016.

  1. A.B.

    A.B. Senior Member

    Messages:
    3,750
    Likes:
    23,193
    No it's not.

    It's https://www.ncbi.nlm.nih.gov/pubmed/9270567

    Anyway, I spotted another methodological issue

    Patients who got significantly worse were effectively removed from the analysis.
     
    Last edited: Dec 13, 2016
    Orla, Jo Best, Woolie and 1 other person like this.
  2. Hip

    Hip Senior Member

    Messages:
    9,949
    Likes:
    15,950
    That is a completely different study, nothing to do with measuring the placebo-induced increase in endogenous dopamine release via PET scans and raclopride binding on dopamine receptors. Endogenous dopamine competes with the raclopride on the dopamine receptor, and pushes raclopride off the receptor, and I believe this is how the PET scan measures endogenous dopamine levels.
     
  3. Woolie

    Woolie Senior Member

    Messages:
    1,931
    Likes:
    14,571
    In this paper, Allan and Siegel offer an interesting explanation for the placebo effect. They suggest that its mostly due to artefact.

    They suggest that evaluating your own symptoms is like a signal detection task - in reality there is lots of noise and fluctuation in the "signal" (that is, your symptoms are always fluctuating in severity etc). When you're asked to make a flat rating of how you were feeling over a longer period - days or weeks- you have to try and ignore the noise and focus on the underlying pattern.

    We know from studies of perception that detecting patterns amongst noise is vulnerable to expectancy effects. A simple example is when someone plays you a recording of a word which clearly ends in "at" but there is a lot of noise that makes the first consonant unclear. If you have recently heard a sentence about animals, you will likely believe you heard "cat" (the word will really sound like cat), whereas if you've heard a sentence about baseball you will more likely believe you heard "bat". The word you "hear" in the noise is biased by your expectations.

    So applying that to judgements about your symptoms, if you expect to see improvement, you will judge the noisy/ambiguous information in favour of "improvement", but if you don't expect to improve, you won't.

    This is such a clever piece of work, I wonder why it doesn't get more attention?
     
    Last edited: Dec 14, 2016
  4. Woolie

    Woolie Senior Member

    Messages:
    1,931
    Likes:
    14,571
    @Hip, this study doesn't count, because they didn't actually measure the placebo effect. They measured the rate of spontaneous improvement in a placebo control group. So its not clear whether the 16% improvement is really due to the "placebo effect" or whether it reflects random fluctuations in the disease course in untreated patients.

    To measure the "placebo effect", you have to do more than document improvement in a placebo control group. You have to compare that control group with another group that knew they weren't getting treatment. And then show that the placebo group improved significantly more than the controls.
     
  5. Sean

    Sean Senior Member

    Messages:
    3,260
    Likes:
    18,001
    That is the core of it: If a study does not contain both a no treatment arm and a placebo arm, then it cannot establish the existence or size of any genuine placebo effect.

    Studies of this form (treatment arm/s + no treatment arm + placebo arm) are the basis of the Hróbjartsson and Gøtzsche meta-analysis on placebo effect size that I cited before.
     
  6. Hip

    Hip Senior Member

    Messages:
    9,949
    Likes:
    15,950
    I think you are right.

    Although you'd have to speak to experts in Parkinson's disease to know whether spontaneous improvements do naturally occur from time to time. Some diseases are prone to natural spontaneous improvements, others have a more steady course.
     
    Skycloud and Barry53 like this.
  7. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,616
    Likes:
    12,462
    South Australia
    corrected link:

    https://www.ncbi.nlm.nih.gov/pubmed/12449084

    I agree with this hypothesis. The placebo effect is more or less just distraction.

    As of this year, there is some evidence to verify this hypothesis:

    http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002570

    So the level of brain connectivity in an area implicated for attentional circuitry predicts the level of placebo response. As far as I know, this is the only study which has confirmed a biomarker for placebo response. (eg predicts placebo responders before the test).

    There were some strange results in that study though, (claims that duloxetine enhanced placebo response in some patients, but reduced it in others -> I don't believe this is valid)
     
    Hip and Sean like this.
  8. Woolie

    Woolie Senior Member

    Messages:
    1,931
    Likes:
    14,571
    @Snow Leopard, this study is kind of a bit weirdly done isn't it? They wanted to look at "placebo responders", but in their original design, they forget to include a non-treatment group to ascertain whether their improving participants were actually showing a placebo effect or just a spontaneous remission (same problem is as the paper described above by Hip).

    So then they tried to make it up by adding in a no treatment group later.

    Also, I'm not sure they can actually claim this:
    They don't seem to have done any direct comparisons between their placebo group and their (later) non-treatment group. This is worrying, because overall, the non-treatment group did show a bit of an improvement. Just not as much as the placebo group.

    Still having said all that, their figs show that the "placebo responder" dropped back after the placebo treatment was terminated, and I found that pretty persuasive that they really were responding to the treatment.

    Note that:
    9 of the 20 placebo group patients were classified as "responders" based on the study's criteria, but:
    7 of the 20 patients in the no treatment study could be classified as "responders" based on the same criter1a
    (so not that impressive, really).

    I'm not sure what to make of the connectivity results. They report that people with high connectivity in the right dorsolateral prefrontal cortex were more likely to show a "placebo effect". This area does a lot of things. Th eproblem is: in any group of 20 odd people split into two subgroups, you would probably find some significant difference in connectivity somewhere in the brain. There are just so many opportunities! So you really need to have a hypothesis ahead of time that predicts this area will be important, to prevent things from degenerating into a fishing expedition.

    The modelling stuff is neat, though.
     
    Snow Leopard, Valentijn and Sean like this.
  9. IreneF

    IreneF Senior Member

    Messages:
    1,552
    Likes:
    2,568
    San Francisco
    How long does the placebo effect last, and how does it change the course of PD?
     
  10. Woolie

    Woolie Senior Member

    Messages:
    1,931
    Likes:
    14,571
    Tricky question, since we're not sure the placebo effect is even "real". It could just be a bias int he way peopel report their health, even when there's no change to their day to day experience whatsoever. But in the study of knee pain that @Snow Leopard mentioned above, it took two weeks for the effect to "wear off".

    You've nailed the real problem though, @IreneF. If you can only induce better self-reported health while you're actually duping people, and the effect wears off after the duping is complete, then its not much practical use to anyone. Even if its a "real" improvement. Its just too short-lived.
     
  11. Sean

    Sean Senior Member

    Messages:
    3,260
    Likes:
    18,001
    Not just merely of no practical use, it is also highly demoralising for patients, generates distrust of legitimate expert medical advice, and is a waste of precious time and energy for everybody.

    All of which leaves patients and broader society far worse off than before, with a much more difficult and expensive problem for the next generation to deal with.

    :grumpy:
     
  12. Hip

    Hip Senior Member

    Messages:
    9,949
    Likes:
    15,950
    Nobody actually deliberately uses the placebo effect in ordinary conventional medicine (or only very rarely), so I cannot see how it would create distrust, or waste of precious time and energy.

    The placebo effect will naturally occur when any active medicine is prescribed by a doctor, on top of the actual pharmacological effects of that medicine; but that's not deliberate use of a placebo, it's incidental. In any case, such incidental application of the placebo effect, if it does help patients feel better, can only be an advantage, I would have thought.
     
  13. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,616
    Likes:
    12,462
    South Australia
    Yes, but it kind of just suggests that the placebo response isn't that impressive. (I admit it confirmed my prior expectations ;))

    They did several studies, one which identified the r-MFG being involved as the primary hypothesis and a second study which confirmed it. This means it wasn't merely a fishing expedition unlike other studies in this field. I didn't think much of the third (observational) study though.
     
  14. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,616
    Likes:
    12,462
    South Australia
    Sadly I beg to differ... There is much debate over the ethics of it right now too.
     
    ahimsa, Valentijn and Sean like this.
  15. adreno

    adreno PR activist

    Messages:
    4,841
    Likes:
    11,033
    Hogwash. Even if we assume that "the placebo effect" happens because of heightened dopamine, this chemical doesn't come out of nowhere. It is produced in neurons – neurons that are dead in parkinson's.

    Your beliefs can't permanently increase dopamine production. This chemical is highly regulated by feedback systems. Yeah, you could enjoy a relative increase for a while, but having sex or eating a desert would probably do the same.
     
    Dichotohmy and Mel9 like this.
  16. Hip

    Hip Senior Member

    Messages:
    9,949
    Likes:
    15,950
    Hmm, it seems that's true. I just did some quick Google searching, and this study about placebo use by GPs in Germany found that 45% of GPs used placebos such as saline injections and sugar pills typically around 5 times a year (which is not actually very much).

    From the study, here are the reasons these placebos were given:


    This survey in the UK found that:
    • 97% of GPs admitted to giving an impure placebo at some point during their career, while 10% had given pure placebos.

    • 1% of GPs used pure placebos at least once a week

    • 77% of GPs used impure placebos at least once a week

    Note: an impure placebo is one that has pharmacological effects, but the effect on the specific disease it is prescribed for has not been proven, or is uncertain.
     
    Isaiah 58:11 likes this.
  17. Sean

    Sean Senior Member

    Messages:
    3,260
    Likes:
    18,001
    This.

    The placebo effect is a temporary generic effect that does not resolve underlying specific problems.
     
    Mel9 and Valentijn like this.
  18. Hip

    Hip Senior Member

    Messages:
    9,949
    Likes:
    15,950
    Here is a question to everyone on this thread:

    I find whenever I read about, or am planning to try, a potentially helpful ME/CFS treatment, be it a drug, supplement or other therapy, this always raises my mood and spirits. It provides me with a nice hopeful, optimistic feeling for a period of some days or weeks. I am talking about the period of time just before you start taking the treatment, for example, when you have just ordered online a new supplement or drug, and are waiting a week or so for it to be delivered.

    Do other people find the same thing? Does having a new treatment on your horizon boost your mood or optimism?

    This may be one reason why ME/CFS patients tend to try out lots of medications. I am not saying that these medications don't work; we all know that now and then you do find a treatment that works for you; but I suspect the mood-boosting and hope-engendering effect of having a new treatment lined up to try in the near future is a factor in why some ME/CFS patients show interest in testing lots of treatments.

    However, this mood and hope raising effect is not the placebo effect as such, as at this stage, you are only planning to take the medication in the near future, you have not yet taken it.


    And in fact, I would say that the when it comes to the actual placebo effect, once I have started taking a new medication, I feel fairly immune to this placebo effect, and feel that I am able to gauge the effects of the new medication I am trying with reasonable accuracy.

    I think this is in part due to the fact that the placebo effect is based on expectation: placebo is based on what you expect the medication to do for you. In my case, and in the case of many ME/CFS patients, I have found that many supplements or drugs actually make one or more of my symptoms worse, sometimes substantially worse, so my expectations regarding a new medication are as much negative as they are positive.

    In other words, I hope the new medication will help, but I am also quite wary that it will worsen symptoms; so this leaves me sort of "expectation neutral," in that I know it could go either way, with the treatment improving or worsening symptoms (and very often more complex situations where the treatment improves some symptoms, but worsens others).
     
    Mel9 likes this.
  19. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,616
    Likes:
    12,462
    South Australia
    I used to feel a bit anxious about side effects, perhaps even a nocebo response, but it always normalised in a few days. Now I've tried so many things that I simply expect things not to work - I need a large change in either energy or reduction of symptoms to notice anything. For example if I woke up without a headache, I'd consider the treatment to be working - but this has never happened in over 15 years. :(
     
    Orla likes this.
  20. Mr. Cat

    Mr. Cat Senior Member

    Messages:
    146
    Likes:
    167
    Nothern California
    Yes, I've noticed a similar experience through the years - feeling better when researching or preparing for a new treatment. I'm a big fan of the placebos of Hope, Optimism, and Magical Thinking, and have tried to modify my thinking to include more of them. For me at least, they give me a guaranteed boost when imagining a positive outcome, with a possible second boost if that outcome ever comes to pass. Earlier in this thread, a poster mentioned that placebos are a mental "distraction" from a measurable medical condition, and effects from placebos have been criticized as being subjective rather than objective. I am very open to mental distractions that improve my subjective reality!
     
    Isaiah 58:11, Sandman00747 and Hip like this.

See more popular forum discussions.

Share This Page