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Dr. Bob is Robert Hsiung, MD,
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Posted by SLS on August 13, 2008, at 15:32:41
In reply to Re: Placebo in Psychiatric Clinical Trials » SLS, posted by Phillipa on August 13, 2008, at 11:02:24
> To me it means that the mind is suggestive and wants to believe.
Yes. And for those people for whom this true, it is possible that they would do well with psychotherapy.
The NIH noticed something remarkable. Most people entering the program report feeling less depressed during the first 2-3 weeks, regardless of treatment. I experienced this. There is something about the idea of being successfully treated in a clinical setting that evokes optimism and the belief that they are to receive better care in the midst of such a large institutional treatment team. I experienced having more energy and optimism, but no true improvement in feelings of depression, anhedonia, and cognitive impairments.
- Scott
Posted by seldomseen on August 13, 2008, at 17:59:47
In reply to Placebo in Psychiatric Clinical Trials, posted by SLS on August 13, 2008, at 7:40:34
I think it could mean a lot of things actually.
It could also mean that 30% of the people in the study would improve without treatment.
It could mean that the study outcome measure is flawed in some way. Usually depression is measured using some kind of metric - like a questionnaire or something. A rather subjective endpoint in my opinion.
It could also mean that the study isn't being implemented in a correct manner, a variable that isn't being appropriately controlled for, blindness breached or something like that.
While the power of suggestion is usually the thing most people suggest, I suspect the "truth" is something far more mundane.
Of course, they could be using Sucrosa ;)
http://www.theonion.com/content/node/39082Seldom
Posted by bleauberry on August 13, 2008, at 19:13:45
In reply to Placebo in Psychiatric Clinical Trials, posted by SLS on August 13, 2008, at 7:40:34
A %: Were about to spontaneously improve anyway. It coincidentally happened at that time.
B %: Got a brain jolt from the excitement of talking with the researchers and going through the whole process and anticipation. It's a big deal, lots of attention and care, got a nice adrenaline boost in it all.
C %: The power of the mind. A true placebo response.
D %: Started sleeping better, eating better, not worrying so much, more energy, now relieved that they are involved in something with hope and promise. So the scores relating to those specific questions on the DSM questionnaire improved to a point that showed a significant overall DSM total score reduction. But, hidden by statistics is that on the other DSM questions about depressed mood and lack of interest in pleasure, they were still severely depressed. The other improved scores relating to sleep, energy, and eating overshadowed that and made it appear falsely that they had improved.
E %: Human error. As smart as we think we are, we do not do anything perfect.
F% : Hidden human subjectivity, politics or economics.
Posted by Dade on August 13, 2008, at 20:59:16
In reply to Placebo in Psychiatric Clinical Trials, posted by SLS on August 13, 2008, at 7:40:34
> Placebo in Psychiatric Clinical Trials
>
>
> I hope this will be an interesting topic.
>
> The rate of placebo response in clinical trials is approximately 30 percent. What does this mean?
>
>
> - Scott
Hi,'You often don't get what you want, you get what you expect'
Posted by Phillipa on August 13, 2008, at 21:30:13
In reply to Re: Placebo in Psychiatric Clinical Trials » SLS, posted by seldomseen on August 13, 2008, at 17:59:47
Seldomseen that link shut down my computer. Might want to check it out Phillipa
Posted by SLS on August 13, 2008, at 22:16:49
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by bleauberry on August 13, 2008, at 19:13:45
Hi BB.
> A %: Were about to spontaneously improve anyway. It coincidentally happened at that time.
My guess is that this happens only occasionally.
> B %: Got a brain jolt from the excitement of talking with the researchers and going through the whole process and anticipation. It's a big deal, lots of attention and care, got a nice adrenaline boost in it all.I believe this is possible, but not probable.
> C %: The power of the mind. A true placebo response.
This is a point of contention. Aren't all responses during placebo administration true placebo responses?
> D %: Started sleeping better, eating better, not worrying so much, more energy, now relieved that they are involved in something with hope and promise. So the scores relating to those specific questions on the DSM questionnaire improved to a point that showed a significant overall DSM total score reduction. But, hidden by statistics is that on the other DSM questions about depressed mood and lack of interest in pleasure, they were still severely depressed. The other improved scores relating to sleep, energy, and eating overshadowed that and made it appear falsely that they had improved.
This is very astute.
> E %: Human error. As smart as we think we are, we do not do anything perfect.
Agreed.
> F% : Hidden human subjectivity, politics or economics.
Interesting.
I think you touched on a very important point. Placebo administration in a clinical setting is not equivalent to "no treatment". The patient is shown a great deal of attention and support. Batteries of tests and a more focused diagnostic procedure captures trust. The patient is convinced that they are getting the best care possible, and finds emotional relief. He becomes optimistic and animated. When questioned how he feels, the patient often replies "better" and will even score better on psychometric tests. Even the socialization that occurs with the investigative staff provides a therapeutic psychosocial intervention for patients who are generally isolating.
Clinical trials usually don't run beyond 8 weeks. As such, these investigations are not longitudinal. It seems that when followed up for longer periods, placebo responders relapse at a much greater rate than drug responders.
Charles Nemeroff on Medscape (registration is free):
http://www.medscape.com/viewarticle/578736?src=mp&spon=12&uac=41170BN
- Scott
Posted by atmlady on August 13, 2008, at 23:12:54
In reply to Placebo in Psychiatric Clinical Trials, posted by SLS on August 13, 2008, at 7:40:34
Here's an interesting except from an interview with Nicholas Humphrey, a "theoretical psychologist", about research he's involved with on the placebo effect:
"Recently I've been involved in research on the placebo effect, coming at it from a mixture of philosophical and evolutionary perspectives. The placebo effect is a very important aspect of all medicine. A large part of medical cures are effected by the patients themselves, when the medical procedure allows the patients to bring their own resources to bear to solve the problem. In the classical placebo case, you give a sugar pill and the patient uses this as an excuse to cure himself. But placebos are actually present in every kind of medical treatment. To the extent the patient believes the treatment is going to work, he allows himself to deploy his own healing resources in a way that he wouldn't have done otherwise.
How should we understand this? What questions should a science of the placebo effect be asking? Of course it's important to investigate the brain mechanisms that underlie these effects, and lots of researchers are already beginning to home in on the problem at the level of neurophysiology and immunology. But it's no less important to look at the bigger picture, and ask: Whatever is going on here, from a functional standpoint? If a placebo is releasing in people an ability to cure themselves, why don't they just get on with it? Why ever should anyone withhold self-cure? You'd think that when you're sick you should just get better if you can; you shouldn't need to wait for permission from a doctor, a shaman, or a psychotherapist to utilize your own resources.
It's this level of question that has set me looking for some possible evolutionary explanation. Why should humans and other animals hold healing resources in reserve? What can be the advantages of not getting better when you actually could? As I've looked further, I've found many examples of it.
People may die from cancer when they have immune resources still waiting in reserve which could have been deployed against the cancer. People die in head-on car collisions because they don't apply the brakes hard enough. When athletes are running a marathon, they may reach the end of what they can do and collapse from fatigue, when, in fact, their muscles still have significant reserves left in them.
What's going on?
You'll have guessed the way I want to go with this: my idea is that nature has designed us to play safe, and never to use up everything we've got because we never know what might still lie around the corner. When we reach the end of a marathon there may still be a lion waiting at the finishing post that's going to suddenly give chase. When we're sick with an infection and respond with an immune reaction, we may still be hit by a further infection the next day. Remember the story of the wise and foolish virgins and their lamps: it's always wise to keep something in reserve.
I'm now thinking in terms of there being what I call a "natural health management system", which does a kind of economic analysis of what the opportunities and the costs of self-cure will be what resources we've got, how dangerous the situation is right now, and what predictions we can make of what the future holds. It's like a good hospital manager who has to choose if and when to throw resources against this or that problem, to hold so much back, to decide if it's essential to build up this area or that area basically to try to produce an optimal solution to the problem of maintaining health with enough left over to meet coming challenges.
If this is right, it makes the placebo effect fit into a much larger picture of homeostasis and health management. And it converges with ideas being developed by researchers coming from quite different disciplines. I've been particularly struck by the work of the South African physiologist, Timothy Noakes, who has come up with the idea of there being what he calls "a central governor" in the brain which regulates just how far the body should be allowed to go in meeting the demands of extreme exercise.
These ideas are big, because they are producing a new perspective on how we and other animals have evolved to manage our internal healing resources across the board. But it already goes much beyond mere theory.
There's a phenomenon, well known to sports physiologists and athletes called "interval training". If you want to improve your prowess as an athlete, one highly effective method of doing it is to build up in the following way. If you're a sprinter, for example, you sprint for two minutes and then relax and jog for five minutes. Then you repeat this pattern again, and again. The result is that you soon find you can run about 15% better than you could before.
Why does this work? According to Tim Noakes, what may be happening is this. In order to improve peak performance you need to persuade your central governor to let you go beyond your own self-imposed limits, when otherwise "cautionary tiredness" would kick in and say, "No more." And one way of doing this is by teaching your central governor that the risks are not actually so great after all. Through interval training you can teach your own brain that you are not going to get into trouble by pushing yourself a little further than you might otherwise have done.
Noakes' theory is a clever way of looking at how to stretch the limits of athletic performance. But what about applying the same idea in other areas? In particular, what about the possibility that we could have interval training for the immune system? If people are not deploying their immune resources to maximum extent, so that they don't get better when they could have, could we teach them by a similar schedule of exercise for the immune system that it's safe to do so?"
Complete interview here:
http://www.edge.org/3rd_culture/humphrey04/humphrey04_index.html
When I was a teenager and was depressed, my mom used to tell me to "take a shower and put on some make-up" or "go take a walk" and I'd feel better, and sometimes it would actually work ('course, the depression always came back, later). This reminds me of the acting "as-if" of AA (I think it's AA). Act like you have ... whatever (love in your life, a reason to live) and eventually you WILL have it, will really have it, that sort of thing.
I wonder if sometimes just doing something different or just doing SOMETHING (changing a med, checking into a hospital, beginning therapy, etc) can release whatever it is that's been holding back our own healing powers (the inner anti-depressant). If that makes ANY sense at all.
Posted by seldomseen on August 14, 2008, at 7:31:01
In reply to Re: Placebo in Psychiatric Clinical Trials » seldomseen, posted by Phillipa on August 13, 2008, at 21:30:13
sorry about that, it is fine on my computer. Besides it was just an attempt at humor anyway.
Posted by Marty on August 15, 2008, at 12:11:04
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by bleauberry on August 13, 2008, at 19:13:45
D% is pretty clever! Well thought.
/\/\arty
---
> D %: Started sleeping better, eating better, not worrying so much, more energy, now relieved that they are involved in something with hope and promise. So the scores relating to those specific questions on the DSM questionnaire improved to a point that showed a significant overall DSM total score reduction. But, hidden by statistics is that on the other DSM questions about depressed mood and lack of interest in pleasure, they were still severely depressed. The other improved scores relating to sleep, energy, and eating overshadowed that and made it appear falsely that they had improved.
Posted by SLS on August 15, 2008, at 12:48:24
In reply to Re: Placebo in Psychiatric Clinical Trials » bleauberry, posted by Marty on August 15, 2008, at 12:11:04
If drug trials were to be carried out for 6 months, I bet the active compound would show itself to be quite a bit more effective than placebo as the placebo responders drop out for having relapsed.
- Scott
Posted by Chris O on August 15, 2008, at 14:14:39
In reply to Placebo in Psychiatric Clinical Trials, posted by SLS on August 13, 2008, at 7:40:34
With my anxiety disorder, I feel personally better just knowing that someone cares about me and is there to support me. I also feel hope if someone outside me believes something will work, even if I don't. It's like that inner "hope" part of me never developed (was not supported) in childhood, so I need someone outside to give that type of validation. However, like you, the core physical symptoms of my disorder basically remain in tact without pharmaceutical intervention.
Posted by Marty on August 15, 2008, at 14:18:39
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by bleauberry on August 13, 2008, at 19:13:45
This post is long but I think it's worth the reading as it present a very different hypothesis of the placebo effect in depression in the context of a very representation of what situational depression really his.
Many things has already been suggested and make sense in this thread. But I'd like to offer a more 'mechanical/systemic' hypothesis that I gave some thought some time ago.
For the sake of simplicity my hypothesis which is in the form of an representation/analogy will limit itself to a SITUATIONAL depression and will not account in details for the types which involve some profound biological pathology like Bipolar Type 1. The 'placebo effect' in the hypothesis/analogy will be described as 'Confidence/Optimism/Hope' and can't be explain without explaining some major parts of this hypothesis. So please stay with me for 10 minutes and I think some of you will find this perspective interesting: What is the placebo effect in the specific context of depression.
PS: While reading the whole thing before posting, I've found it way more interesting/entertaining imagining George Carlin voicing it in my head. You may want to try that!
[ (the basic lines of) The Government Hypothesis of Depression ]
The brain is acting like a government which governs a body (analogy: country/enterprise) and you, the consciousness, would be his submissive executive president. This goverment work toward some objectives which include survial and reproduction. And that's why :
1. When things ain't going well: Parts of the governement thinks it's because of you or MAYBE IT'S NOT BUT maybe you could do something about it and so, based on that logic, here's the politics/strategies of the government in those instance:
1.1: Pressure in the form of sanctions(mental pain/discomfort) are put upon you to punish you for what you shouldn't never do again OR/AND make sure you do something about the current situation/aftermath. Evaluating IF you can actually do something about it isn't something the government do as well as you, the executive president (consciousness), you are the one who usually can evaluate something as complex because of your higher intelligence but in this case your input about if you can do something isn't very much taken into account for that the government confidence in you is pretty low in those circumstances.. and so no chances are taken and pressure will be systematicly put on you to make sure you will do everything you can as fast as possible: systematic pressure in the form of pain is the strategy that millions years of evolution found out to be the best in those case. After all, without pain.. you wouldn't be that fast to remove your foot on the nail you just stepped on, right ?
1.2: The situation being bad and prospect of a better future not currently forseeable by the government, extreme budgeting mesures are taken to increase survival chances AND confidence toward your abilities to lead being very low, your executive powers/influence on the government and body are inhibited as to reduce the risk that you agrave further the situation. Your executive powers/influence being reduce also contribute to reduce your ability to reverse the extreme bugeting mesures.
---> 1.1 + 1.2 = Situational Depression: Lost of confidence + Pressure on you + Inhibition of your powers/leadership + ressource budgeting.
Now to the point: where is the placebo effect in this hypothesis ? The government feels that you may well have found a solution to the situation in the form of 'X' treatment (let's say a new pill) to the crisis. And that's because of one of the very simplistic way he allow himself to evaluate possible solutions -> Possible pain reduction. The government consider that the ->president evaluation<- of what could reduce pressure on him (pain) is a good marker of a possibly good solution. ... AND NOW THAT THE GOVERNMENT THINKS THAT YOU MAY WELL BE ABOUT TO IMPROVE THE SITUATION -> A CONFIDENCE BOOST IS IN ORDER (LESS PRESSURE IN THE FORM OF PAIN) AND PARTIAL RESTABLISHMENT/DESINHIBITION OF YOUR EXECUTIVE POWERS IS ALSO IN ORDER TO INCREASE YOUR CHANCES OF SUCCESS IN YOUR PURSUIT OF YOUR 'POSSIBLY GOOD' SOLUTION.
SO in summary: The depression being voluntary induced upon itself and the consciousness (you) by the brain.. The prospect of a possibly good solution (the pill that is in fact a placebo) being applied or soon to be applied leads to a ->strategic relieves<- of the depression symptoms. After a while, depending if you used that relieves to *really* improve the situation or not, the brain gradually or quickly catch up to the fact that nothing really improved in your ability to attain his objectives and so depression is, usually, reintroduce fully.
Did you really read to that point ?! ;)
Let me think what you think of this representation point of view. What doesn't fit ?BTW, the analogy with president and government is used to simplify the way mother nature possibly made us. I'm not seing the whole thing as simplistic as that in my head, obviously.
/\/\arty
Poorly rated C.E.O of the "United Systems of /\/\arty" which responsabilities includes the successful reproduction and survival of the "USM" genes by mastering every life variables judged by the goverment to be markers of improved chances of success.... damn, I'm not paid enought for that job !!!! ..maybe that explains why I sometime flirt with the idea of **resignation** ..........
Posted by Chris O on August 15, 2008, at 14:24:53
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by Marty on August 15, 2008, at 14:18:39
Yes, this an apt description for me, with my mother functioning as the government or super-ego. Dang, why did I have to grow up under a dictatorship and not a democracy?!
I think that theory has political implications too, regarding how large populations of people became brain damaged and are made mentally ill by the type of government/religion/organizing paradigm under which they live.
Posted by Marty on August 15, 2008, at 14:49:54
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by Chris O on August 15, 2008, at 14:24:53
Hi Chris,
> Yes, this an apt description for me, with my mother functioning as the government or super-ego. Dang, why did I have to grow up under a dictatorship and not a democracy?!
>
> I think that theory has political implications too, regarding how large populations of people became brain damaged and are made mentally ill by the type of government/religion/organizing paradigm under which they live.
----Interesting the links you made while reading my post. That said I think you didn't quite understood that it was a representation based on an analogy. In my post it is the brain which is compared to a government. In my entire post I didn't use the work government to refer to an actual government let alone an actual government of the mentally ills. But it's quite easy to get lost while reading this ! .. and my written english limits me and give ways to some pretty obscur explaination sometimes :P
See ya,
/\/\arty
Posted by Chris O on August 15, 2008, at 15:15:21
In reply to Re: Placebo in Psychiatric Clinical Trials » Chris O, posted by Marty on August 15, 2008, at 14:49:54
Marty:
I think I get the analogy. You were saying the brain acts as a kind of punitive government structure, creating conditions of depression and anxiety in some people, right? I was just, somewhat sarcastically, pointing out the origins of my brain's "government" (the way my mother treated me growing up). And I was just extending the analogy to how the "brain governments" of larger populations could be shaped depending on the conditions under which they live/were raised.
Chris
Posted by Marty on August 15, 2008, at 15:37:37
In reply to Re: Placebo in Psychiatric Clinical Trials » Marty, posted by Chris O on August 15, 2008, at 15:15:21
> I think I get the analogy. You were saying the brain acts as a kind of punitive government structure, creating conditions of depression and anxiety in some people, right? I was just, somewhat sarcastically, pointing out the origins of my brain's "government" (the way my mother treated me growing up). And I was just extending the analogy to how the "brain governments" of larger populations could be shaped depending on the conditions under which they live/were raised.
---LOL. Sorry Chris; you do get the analogy perfectly! I guess I'm kind of used to be misinterpreted because of my english.. loll
Again, yes, you're ideas on how the representation can be expanded to other system could be interesting.
/\/\arty
Posted by SLS on August 15, 2008, at 15:57:28
In reply to Re: Placebo in Psychiatric Clinical Trials » Marty, posted by Chris O on August 15, 2008, at 15:15:21
I think that it is important to conduct clinical trials using subjects whom are properly diagnosed as having Major Depressive Disorder (MDD). I believe you would see a greater separation in response rates between placebo and active compounds.
- Scott
Posted by SLS on August 15, 2008, at 16:00:05
In reply to Re: Placebo in Psychiatric Clinical Trials » Chris O, posted by Marty on August 15, 2008, at 15:37:37
Dear Marty,
There is nothing wrong with your English. In fact, I am in awe of your ability to use it so well.
No more excuses!
:-)
- Scott
Posted by Marty on August 15, 2008, at 16:30:04
In reply to Re: Placebo in Psychiatric Clinical Trials » Marty, posted by SLS on August 15, 2008, at 16:00:05
> Dear Marty,
>
> There is nothing wrong with your English. In fact, I am in awe of your ability to use it so well.
>
> No more excuses!
>
> :-)
---
Ahahah Thanks Scott :) .. and also thanks to this board for having allowed me to improve alot in the last couple years!Btw, your english's not bad too! Where are you from ?
.
.
....... just kidding ;)
/\/\arty
Posted by Jamal Spelling on August 15, 2008, at 16:38:39
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by SLS on August 15, 2008, at 15:57:28
> I think that it is important to conduct clinical trials using subjects whom are properly diagnosed as having Major Depressive Disorder (MDD). I believe you would see a greater separation in response rates between placebo and active compounds.
>
>
> - ScottI agree. Those pesky placebo responders keep ruining the data.
Posted by SLS on August 15, 2008, at 18:32:29
In reply to Re: Placebo in Psychiatric Clinical Trials » SLS, posted by Jamal Spelling on August 15, 2008, at 16:38:39
> > I think that it is important to conduct clinical trials using subjects whom are properly diagnosed as having Major Depressive Disorder (MDD). I believe you would see a greater separation in response rates between placebo and active compounds.
> >
> >
> > - Scott
>
> I agree. Those pesky placebo responders keep ruining the data.
LOL Very good. :-)My guess is that people whose depression is not of a biological diathesis are more apt to report a placebo response. Frederick Quitkin, MD, who died not too long ago, devoted much of his work to describing the placebo response and how it affects the interpretation of data. You can find his work on Google or Medline.
He was a real smart guy, but I wasn't too happy with his bedside manner.
- Scott
Posted by Marty on August 15, 2008, at 19:15:46
In reply to Re: Placebo in Psychiatric Clinical Trials » SLS, posted by Jamal Spelling on August 15, 2008, at 16:38:39
They should do double-blind clinical trials where NOBODY WOULD BE TOLD WHAT THEY ARE TAKING. Or LIE about the purpose of what they take.. something like "It is to improve the quality of the results from the brain scan we'll do on you each day. Like you already know the purpose of this study is the brains of sick and normal people." .. eh voila... now you check for the symptoms, general health and side effects like you would do in normal clinical trials. And you, obviously, fake some kind of scan.What about the 'Authorizations/Consents' ? That's another story but I'm sure that could worked out somehow. Maybe by having the patient agreeing to do 2 studies: the first one to study his brain and the second one 6 months later to try the antidepressant ! .. he agrees to both and while you tell him he is starting the 'brain study' one you do the other on him !
I think I would pay to know the results to such clinical trials ! Any placebo response would have to do with the setting (better life hygiene, support, food etc) .. :)
/\/\arty
Posted by Cecilia on August 16, 2008, at 7:27:20
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by Marty on August 15, 2008, at 19:15:46
I don't think an accurate placebo trial is possible with psych drugs. Most have so many side effects that people can easily figure out if they're on the real thing. (And so can their doctors, which destroys the double blind effect). Sure, people report side effects with placebos, but generally they're common things in everyday life, headaches, insomnia etc. If people get side effects they've rarely had before they know it's pretty likely they're on the real drug. Cecilia
Posted by SLS on August 16, 2008, at 7:38:47
In reply to Re: Placebo in Psychiatric Clinical Trials, posted by Cecilia on August 16, 2008, at 7:27:20
> I don't think an accurate placebo trial is possible with psych drugs. Most have so many side effects that people can easily figure out if they're on the real thing. (And so can their doctors, which destroys the double blind effect). Sure, people report side effects with placebos, but generally they're common things in everyday life, headaches, insomnia etc. If people get side effects they've rarely had before they know it's pretty likely they're on the real drug. Cecilia
Some astute investigators use a placebo that produces side effects but has no antidepressant properties. Low dosages of the anticholinergic Cogentin would be an example. The term for this strategy is "active placebo".
- Scott
Posted by Cecilia on August 16, 2008, at 17:34:34
In reply to Re: Placebo in Psychiatric Clinical Trials » Cecilia, posted by SLS on August 16, 2008, at 7:38:47
Just curious-have you ever heard of a study sponsored by a drug company, not an independent research agency, using an active placebo? I rather doubt it. The drug companies have a strong incentive to have patients and their doctors know whether they're on the real drug and respond according to their expectations.
Cecilia
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