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Dr. Bob is Robert Hsiung, MD,
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Posted by Larry Hoover on September 13, 2007, at 13:51:57
In reply to Re: STAR*D study, 33% sucess with first AD-sam123, posted by Larry Hoover on September 13, 2007, at 11:54:09
In response to these:
"I can argue that placebos work as well as antidepressants in most clinical trials becuase that is fact based."
"...if all popular ADs in the world were secretly replaced with sugar pills and no one was aware, the success rates of these pills would continue be the same."
"I have come to conclusion after long thought that pdoctors around the world should provide placebo instead of antidepressants in the best interest of patients."I believe these conclusions to be unsupported by the available evidence. If these statements were true, what would we find when we looked at the placebo-controlled clinical trial data?
If we assume equivalence between an antidepressant drug and placebo, then under the statistical assumptions that govern what we call 'significance', 19 times out of 20, there would be no significant difference between the two experimental groups. When we look at all available clinical trial data, including all the studies that were never published, is this the case? No.
Under those same assumptions, assuming equivalence, both placebo and the antidepressant should have similar frequency of being found to be statistically superior to the other. Is this the case? No.
But there are other ways to look at the data. We can rank them, even those studies where significant superiority was not obtained. If equivalent, then placebo and the antidepressant should have a similar likelihood of being superior. Is that the case? No. Mean, median, t-test, I don't care how you look at it, antidepresants and placebo are not found to be equivalent.
I've previously argued that you cannot form conclusions about equivalence from obtaining null results in clinical trials. There are a number of reasons why that is so. One is that you cannot know if you conducted an otherwise valid study, but used the wrong subjects. Nor can you know from the results if your methodology was sound. Nor can you exclude chance. You don't know if there wasn't a difference to be found, only that you failed to find one, under the conditions employed. Again, the scientific aphorism, "The absence of evidence is not evidence of absence."
There is no disorder known to man that exhibits a more robust placebo response in clinical trials than does major depression. In a clinical trial you get validation, attention, a chance to be heard, empathy. So maybe some people do just need more love, and that's a big reason why they're exhibiting depression. For others, the difficulty might be more 'mechanical', i.e. biochemical in nature. Lumping both groups together in a clinical trial is going to dilute the effect of a biological intervention. It just stands to reason.
Lar
Posted by polarbear206 on September 13, 2007, at 14:20:18
In reply to placebo vs. antidepressant, posted by Larry Hoover on September 13, 2007, at 13:51:57
> In response to these:
>
> "I can argue that placebos work as well as antidepressants in most clinical trials becuase that is fact based."
> "...if all popular ADs in the world were secretly replaced with sugar pills and no one was aware, the success rates of these pills would continue be the same."
> "I have come to conclusion after long thought that pdoctors around the world should provide placebo instead of antidepressants in the best interest of patients."
>
> I believe these conclusions to be unsupported by the available evidence. If these statements were true, what would we find when we looked at the placebo-controlled clinical trial data?
>
> If we assume equivalence between an antidepressant drug and placebo, then under the statistical assumptions that govern what we call 'significance', 19 times out of 20, there would be no significant difference between the two experimental groups. When we look at all available clinical trial data, including all the studies that were never published, is this the case? No.
>
> Under those same assumptions, assuming equivalence, both placebo and the antidepressant should have similar frequency of being found to be statistically superior to the other. Is this the case? No.
>
> But there are other ways to look at the data. We can rank them, even those studies where significant superiority was not obtained. If equivalent, then placebo and the antidepressant should have a similar likelihood of being superior. Is that the case? No. Mean, median, t-test, I don't care how you look at it, antidepresants and placebo are not found to be equivalent.
>
> I've previously argued that you cannot form conclusions about equivalence from obtaining null results in clinical trials. There are a number of reasons why that is so. One is that you cannot know if you conducted an otherwise valid study, but used the wrong subjects. Nor can you know from the results if your methodology was sound. Nor can you exclude chance. You don't know if there wasn't a difference to be found, only that you failed to find one, under the conditions employed. Again, the scientific aphorism, "The absence of evidence is not evidence of absence."
>
> There is no disorder known to man that exhibits a more robust placebo response in clinical trials than does major depression. In a clinical trial you get validation, attention, a chance to be heard, empathy. So maybe some people do just need more love, and that's a big reason why they're exhibiting depression. For others, the difficulty might be more 'mechanical', i.e. biochemical in nature. Lumping both groups together in a clinical trial is going to dilute the effect of a biological intervention. It just stands to reason.
>
> Lar
Larry,The last paragraph speaks volumes. My thoughts exactly!!!
Thanks,
Polarbear
Posted by linkadge on September 13, 2007, at 16:26:28
In reply to Re: News - Antidepressants Vindicated? » linkadge, posted by Larry Hoover on September 12, 2007, at 9:49:29
>No, again, because these are population >statistics. We don't need to know which subjects >were identified and which were not, nor which >were treated and which were not.
But my point is that without other factors to consider statistically, one can only wonder how the suicide rate increased so disproportionately to the reduced rate in suicide. The argument, "other factors are involved" can be used either way.
Linkadge
Posted by linkadge on September 13, 2007, at 16:28:27
In reply to Re: News - Antidepressants Vindicated? » linkadge, posted by Larry Hoover on September 12, 2007, at 9:50:59
>The data for 2005 will be available in December >of this year. We'll know soon enough
This data will still be too soon to make assumptions. If people are killing themselves so quickly after the reduced rate of suicide, they are probably dying in a manner ala Tracy Johnson.
Linkadge
Posted by linkadge on September 13, 2007, at 16:29:03
In reply to Re: News - Antidepressants Vindicated? » linkadge, posted by Larry Hoover on September 12, 2007, at 9:50:59
>The data for 2005 will be available in December >of this year. We'll know soon enough
This data will still be too soon to make assumptions. If people are killing themselves so quickly after the reduced rate of prescription, they are probably dying in a manner ala Tracy Johnson.
Linkadge
Posted by linkadge on September 13, 2007, at 16:31:04
In reply to Re: News - Antidepressants Vindicated? » linkadge, posted by Larry Hoover on September 12, 2007, at 10:25:34
>They really didn't know how to do them, early on
You got that right. The longer it goes like this the more the drug companies know how to design winning trails.
Linkadge
Posted by linkadge on September 13, 2007, at 16:39:59
In reply to Re: News - Antidepressants Vindicated?))SAM » jhj, posted by Larry Hoover on September 13, 2007, at 9:16:25
>If placebo pill is able to work as well as ADs >with out any side effect then,why people should >be made suffer from the side effects and >increased risk of suicidal tendancies? Thanks.
Exactly. Placebos do generally work as well as antidepressants to the point where **seriuos** thought goes into strategies to beat the placebo. Also, active placebos work better than placebos. That is why their use is fiercely opposed.
BTW. The logic, "I know I my drug works and thats all that matters" is true, but flawed.
I read an article on just how *shocked* many people are in clinical trials when they find out they have been receving the placebo. They say things like "there must be some mistake". "This can't be, I know I was getting the active drug, I could feel it", and on and on the list goes.
The problem is studies have shown the exact same pattern of bloodflow changes when somebody responds to an AD or a placebo. So, a placebo response is generally going to be impossable to pin down.
So, "I know it works" is not enough. Placebo responders know their drugs work too!!
Linkadge
Posted by linkadge on September 13, 2007, at 16:40:46
In reply to Re: STAR*D study, 33% sucess with first AD-sam123 » jhj, posted by Larry Hoover on September 13, 2007, at 9:26:06
>The methodology for this study is entirely >different than that used for placebo-controlled >clinical efficacy trials.
Exactly, thats why I don't care for the STAR*d.
Linkadge
Posted by linkadge on September 13, 2007, at 16:43:33
In reply to placebo vs. antidepressant, posted by Larry Hoover on September 13, 2007, at 13:51:57
>If these statements were true, what would we >find when we looked at the placebo-controlled >clinical trial data?
We might find analysis like this:
http://www.vaccinationnews.com/DailyNews/June2002/CanPlacebo25.htm
In a soon to be published study, Dr. Arif Khan, a psychiatrist at the Northwest Clinical Research Center in Washington, analyzed the Food and Drug Administration's database of 52 clinical trials in depression, involving nine new antidepressants, conducted from 1985 to 2000. ***Since the agency requires drug companies to report all data from all studies for drugs under development, the database can give a more accurate picture of a new drug's efficacy than the medical journals***, where positive findings are far more likely to be reported than negative ones.
Dr. Khan found that in only 48 percent of the 52 clinical trials was the antidepressant superior to the placebo.
Linkadge
Posted by linkadge on September 13, 2007, at 16:51:19
In reply to Re: placebo vs. antidepressant » Larry Hoover, posted by polarbear206 on September 13, 2007, at 14:20:18
>There is no disorder known to man that exhibits >a more robust placebo response in clinical >trials than does major depression. In a clinical >trial you get validation, attention, a chance to >be heard, empathy. So maybe some people do just >need more love, and that's a big reason why >they're exhibiting depression. For others, the >difficulty might be more 'mechanical', i.e. >biochemical in nature. Lumping both groups >together in a clinical trial is going to dilute >the effect of a biological intervention. It just >stands to reason.
A simpler explaination is the fact that depression is one of the few diseases where you are better when you say you are better. Most other diseases have some form of objective measurement involved.
Linkadge
Posted by Larry Hoover on September 13, 2007, at 18:00:20
In reply to Re: placebo vs. antidepressant » Larry Hoover, posted by linkadge on September 13, 2007, at 16:43:33
> >If these statements were true, what would we >find when we looked at the placebo-controlled >clinical trial data?
>
> We might find analysis like this:
>
> http://www.vaccinationnews.com/DailyNews/June2002/CanPlacebo25.htm
>
> In a soon to be published study, Dr. Arif Khan, a psychiatrist at the Northwest Clinical Research Center in Washington, analyzed the Food and Drug Administration's database of 52 clinical trials in depression, involving nine new antidepressants, conducted from 1985 to 2000. ***Since the agency requires drug companies to report all data from all studies for drugs under development, the database can give a more accurate picture of a new drug's efficacy than the medical journals***, where positive findings are far more likely to be reported than negative ones.
>
> Dr. Khan found that in only 48 percent of the 52 clinical trials was the antidepressant superior to the placebo.
>
> LinkadgeI think it's pretty important to also consider the rest of the text from your referenced article. Beginning with the next sentence after the part you copied:
"Does this really mean that antidepressants are on average no better than placebos for depression? In a word, no....
It turns out that the more severely depressed people are, the less likely they are to respond to a placebo. And people with more mild depressions get better with just about all treatments, including placebos. Since most clinical trials enroll less severely depressed patients, the observed difference between the response to an antidepressant and a placebo can be misleadingly small......it is easy to pick a group of mildly depressed patients and show that a placebo is equivalent to an antidepressant.....
There are other reasons that researchers may mistakenly conclude that placebos are as effective as antidepressants. For example, at least nine clinical trials included in Dr. Khan's meta-analysis lasted only four to five weeks. Yet we know that it can take up to six weeks and more for someone with depression to respond to an antidepressant. For example, studies have shown that about half of patients who had not improved after four weeks of antidepressant treatment responded by Week 6. So studies of short duration can exaggerate the efficacy of placebos.....But why does it matter whether a depressed patient gets better on a placebo or an antidepressant? Isn't the mere fact of improvement proof of efficacy? Well, the problem is that the placebo effect is only short-lived, while depression tends to be a chronic illness with a variable rate of recurrence. Patients who continue on placebos have more than double the risk of relapse to depression than those who stay on antidepressant medication.....At best, a placebo may give the patient a temporary boost if he is mildly depressed, but in a seriously depressed patient, it is right in more ways than one to call it a dummy pill."Lar
Posted by Larry Hoover on September 13, 2007, at 20:04:04
In reply to Re: placebo vs. antidepressant » Larry Hoover, posted by linkadge on September 13, 2007, at 16:43:33
> Dr. Khan found that in only 48 percent of the 52 clinical trials was the antidepressant superior to the placebo.
>
> LinkadgeI've looked far and wide, and I can't find the full-text of the above. If anybody knows of it, please let me know.
I like Khan's work. Very straight forward. Doesn't overinterpret his findings. Anyway, I've collected a few brief blurbs from some of his abstracts, all reviews of that same FDA database. My comments, if any, in square parentheses[].
"A statistically significant positive correlation was seen between placebo and antidepressant response magnitude (r =.40, p <.001) and between placebo response magnitude and the advantage of antidepressants over placebo (r = -.592, p <.0001). Only 21.1% of antidepressant treatment arms in trials with high placebo response (>30% mean change from baseline) showed statistical superiority over placebo compared with 74.2% in trials with a low placebo response (< or =30)." [The placebo response is more variable than the antidepressant response.]
"In the flexible dose trials, 59.6% (34/57) of the antidepressant treatment arms were statistically significant compared to placebo, whereas in the fixed dose trials only 31.4% (11/35) of the antidepressant treatment arms were statistically significant compared to placebo (chi(2)=6.9, df=1, p<0.01). These data suggest that the antidepressant dose schedule may influence trial outcome due in part to a significantly lower magnitude of symptom reduction with placebo in flexible dose trials (F=4.08, df=1, 48, p&<0.05) compared to fixed dose trials." [fascinating!]
In this one, my comments are embedded:
"The severity of depressive symptoms before patient randomization [more severe syptoms, greater difference between antidepressant and placebo], the dosing schedule [flexible dosing greater difference to placebo than fixed dose], the number of treatment arms [more treatment arms, greater difference], and the percentage of female patients [more females, greater placebo response, and lower difference] were significantly associated with the difference in response to antidepressant and placebo.""In the antidepressant-treated groups, the magnitude of symptom reduction was significantly related to mean initial Hamilton Rating Scale for Depression (HAM-D) score; the higher the mean initial HAM-D score, the larger the change. With placebo treatment, however, the higher the mean initial HAM-D score, the smaller the change." [redundant, but more explicit]
Thought-provoking, all in all.
Lar
Posted by sam123 on September 13, 2007, at 22:51:11
In reply to Re: placebo vs. antidepressant » linkadge, posted by Larry Hoover on September 13, 2007, at 20:04:04
>
> Thought-provoking, all in all.
>
> Lar
>
>Emperor ? Clothes ?
Posted by sam123 on September 13, 2007, at 23:21:12
In reply to Re: News - Antidepressants Vindicated?))SAM, posted by linkadge on September 13, 2007, at 16:39:59
>
> BTW. The logic, "I know I my drug works and thats all that matters" is true, but flawed.
>
I have tried a whole lota meds over several decades; some do nothing, some are annoying,
and some really do something.
Posted by jhj on September 14, 2007, at 0:01:10
In reply to Re: STAR*D study, 33% sucess with first AD-sam123, posted by sam123 on September 13, 2007, at 8:31:15
I disagree with that point and will post what I like where I like.You have misunderstood me.I am not stoping you from making any point.I mentioned about the thread in which i mentioned the findiings of star*d study and the responses i got.I completely endorse the findings of the study and i wrote in lighter vein about not mentioning. it.I think it was one of the most comprehensive study ever conducted on depression.
Posted by jhj on September 14, 2007, at 0:04:57
In reply to Please follow board guidelines » jhj, posted by Deputy Racer on September 13, 2007, at 12:51:26
Please do not mention about STAR*D study here.You read the comments made on STAR*D study here in reponse to another thread.I wrote the thing only lightly if you read entire post.I have no problem with any study conducted by anybody and certainly about the study which is conducted on such large scale like star*d.I did not find it objectionable to mention the study at all. that is why i did not use the notify the administrator button.Thanks.
Posted by jhj on September 14, 2007, at 0:26:09
In reply to placebo vs. antidepressant, posted by Larry Hoover on September 13, 2007, at 13:51:57
I believe these conclusions to be unsupported by the available evidence. If these statements were true, what would we find when we looked at the placebo-controlled clinical trial data?
If we assume equivalence between an antidepressant drug and placebo, then under the statistical assumptions that govern what we call 'significance', 19 times out of 20, there would be no significant difference between the two experimental groups. When we look at all available clinical trial data, including all the studies that were never published, is this the case? No.
Under those same assumptions, assuming equivalence, both placebo and the antidepressant should have similar frequency of being found to be statistically superior to the other. Is this the case? No.
But there are other ways to look at the data. We can rank them, even those studies where significant superiority was not obtained. If equivalent, then placebo and the antidepressant should have a similar likelihood of being superior. Is that the case? No. Mean, median, t-test, I don't care how you look at it, antidepresants and placebo are not found to be equivalent.
I've previously argued that you cannot form conclusions about equivalence from obtaining null results in clinical trials. There are a number of reasons why that is so. One is that you cannot know if you conducted an otherwise valid study, but used the wrong subjects. Nor can you know from the results if your methodology was sound. Nor can you exclude chance. You don't know if there wasn't a difference to be found, only that you failed to find one, under the conditions employed. Again, the scientific aphorism, "The absence of evidence is not evidence of absence."
There is no disorder known to man that exhibits a more robust placebo response in clinical trials than does major depression. In a clinical trial you get validation, attention, a chance to be heard, empathy. So maybe some people do just need more love, and that's a big reason why they're exhibiting depression. For others, the difficulty might be more 'mechanical', i.e. biochemical in nature. Lumping both groups together in a clinical trial is going to dilute the effect of a biological intervention. It just stands to reason.
I am not saying it that placebo work as well as antidepressant.I am merely quoting from the one previous post to this same thread.
"but I can argue that placebos work as well as antidepressants in most clinical trials becuase that is fact based.
Linkadge"I am neither saying that placebo work as well as antidepressant nor am i saying that ADS incerase suicide risk.I am merely saying that if the statement i have quoted from previous post is assumed true then people should not be prescribed ADs.My belief is that ADs are more effective then placebos and they do not increase the suicide rates.
Posted by jhj on September 14, 2007, at 0:38:49
In reply to Re: STAR*D study, 33% sucess with first AD-sam123 » Larry Hoover, posted by linkadge on September 13, 2007, at 16:40:46
Sam,I have nothing against STAR*D study.I was just quoting link's view on star*d study.Now you can find them here too.
"Exactly, thats why I don't care for the STAR*d.
Linkadge"
Posted by Larry Hoover on September 14, 2007, at 8:52:21
In reply to Re: STAR*D study, 33% sucess with first AD-sam123 » Larry Hoover, posted by linkadge on September 13, 2007, at 16:40:46
> >The methodology for this study is entirely >different than that used for placebo-controlled >clinical efficacy trials.
>
> Exactly, thats why I don't care for the STAR*d.
>
> LinkadgeWhat troubles you about it?
Lar
Posted by Larry Hoover on September 14, 2007, at 9:15:44
In reply to Re: placebo vs. antidepressant, posted by sam123 on September 13, 2007, at 22:51:11
> >
> > Thought-provoking, all in all.
> >
> > Lar
> >
> >
>
> Emperor ? Clothes ?It strikes me that if placebo response is adversely influenced by e.g. flexible dosing, whereas antidepressant response is enhanced (and more like standard clinical practise, also), then we might actually find methodologies to strip away the artefact of clinical trial structure, and reveal the medication effect itself. Well, at least do a better job of it.
IMHO, depression is multifactorial in etiology. Even with a genetic predisposition, environmental factors are powerful modulators. Even if one assumes a purely biological depression, one would never lose one's humanity, i.e. responsiveness to personal attention, caring, support, and love.
In comparisons between studies, Khan (and many others, but I didn't reference them) discovered highly significant correlations between placebo response and antidepressant response. Both tended to be lower, or both tended to be higher. This covariance has the unfortunate mathematical effect of obscuring the drug effect in the more responsive trial environments, despite findings overall that more people found remission.
The gender bias towards placebo response in women also surprised me. I can think of sociological explanations, such as persistance of the dismissive treatment of women from earlier times (now more subtly applied, I'd imagine), or differential response to social cues.
The bias towards selecting moderately depressed subjects with no comorbid conditions actually predisposed towards placebo responsiveness.
The overall point is that everyone is concluding the drugs don't work, without considering the effects of the methodology. We don't know the effects of the methodology, but those effects are non-zero, and always act to obscure the true medication effect. They diminish our ability to see the truth.
Lar
Posted by sam123 on September 14, 2007, at 9:40:46
In reply to Re: placebo vs. antidepressant » sam123, posted by Larry Hoover on September 14, 2007, at 9:15:44
>
> The overall point is that everyone is concluding the drugs don't work,What saddens me is again and again people have posted in this tread and others about their successes, some long term, with AD's and other psycomeds. This seems to be falling on death ears and we have to resort to agruing about studies and methodology despite have proof right here that
at least from some these drugs are no placebos.
Posted by rskontos on September 14, 2007, at 11:05:17
In reply to Re: placebo vs. antidepressant, posted by sam123 on September 14, 2007, at 9:40:46
In my humble opinion, and I am only going on my experience, if I had been in the clinical trials, at the beginning I would have said the AD or whatever I was taking was working because at first it made me feel better than I was feeling at that point but over time, the effects wore off. So my overrall conclusion was that particular AD did not work. Now did it always not work and did I assume it worked because I wanted it too because I was so tired of feeling bad, perhaps, was I in a suggestive mind set because the doctor said this drug works well and in my mind I set great store by her in my faith in her to provide something to work, maybe. I wanted to get better and fast. Whatever the case maybe be and a placebo may have made me feel better at that particular time too because I wanted it badly, I was so low and hurting. She listened too. No one else was. I never trusted anyone too. This was the first time I asked for help too. I have asked myself all these questions while reading this thread, I might have gotten initally better on a placebo or AD at first but it wasn't maintained and then I got worse. So I concluded that the AD did not work. I think AD's work for some, I have friends on them and they have been on them for years and have tried many. So I guess they work for them. I do believe each body handles things diffferently as I can take certain pain meds and they do nothing regardless how many I take. Why I can't guess. I have tried many different migraine meds over the years and take one most people can't take so I draw the conclusion that drugs must work differently in different people. Thanks for education and the thought provoking discussion. RK
Posted by fuzz54 on September 14, 2007, at 12:17:46
In reply to Re: News - Antidepressants Vindicated?, posted by linkadge on September 9, 2007, at 12:21:58
> >Anti-depressants work for many depressed people. >Thus anti-depressants reduce the risk of suicide.
>
> Placebos work for many people too.
>
> LinkadgeI was told by my therapist (who is now a doctor doing psych research) that the placebo effect can be very real in the short-term but loses its effectiveness over the long-term. Anyone ever see any studies on this?
As for SSRIs being compared to placebos in effectiveness, I've been on some SSRIs that did nothing for me and some that helped quite a bit. I didn't have any special knowledge that made me expect some SSRIs to work and some to not work. For my specific case this leads me to conclude that SSRIs work better than placebo, however I am willing to concede that there are many factors at work in determining if someone will respond to an SSRI better than placebo. Maybe I'm just lucky.
fuzz
Posted by linkadge on September 14, 2007, at 13:59:12
In reply to Re: STAR*D study, 33% sucess with first AD-sam123 » linkadge, posted by Larry Hoover on September 14, 2007, at 8:52:21
>What troubles you about it?
No placebo arm.
Thats what little there is left to keep serious dogma in check.
Linkadge
Posted by linkadge on September 14, 2007, at 14:12:54
In reply to Re: placebo vs. antidepressant, posted by rskontos on September 14, 2007, at 11:05:17
Placebos aren't the only things to loose effectiveness over time.
Antidepressant "poop out" is being studied more and more.
Thats probably the biggest complaint we have here: "such and such a drug worked, and now it no longer works".
Tollerance to a pharmachological effect is one possability, loss of placebo effect is another.
Linkadge
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