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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 15 to 39 of 75. Go back in thread:
Posted by chumbawumba on May 11, 2009, at 19:10:06
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by Larry Hoover on May 11, 2009, at 8:12:22
> I'm sorry, but that Kirsch et al study is complete garbage. I offered a detailed critique of it here: http://www.dr-bob.org/babble/20080221/msgs/815551.html
>
> There were other significant criticisms that ended up in other posts, but this was my main set of issues with it.
>
> I really wish this man would go away. He gives a bad name to cherry-pickers. (Cherry-picking is the act of mining statistics for the rare examples that support an argument that is contradicted by the body of the evidence.)
>
> LarI read your critique and don't really have a strong feeling one way or the other about the study, but it does seem like you have a dog in this fight.
The phrase "I have profound contempt for this latest work." just makes me think you're pro-medication? Just a wild guess. Nothing wrong with that, it just suggests a bias.
Posted by Larry Hoover on May 11, 2009, at 20:22:53
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by chumbawumba on May 11, 2009, at 19:10:06
> The phrase "I have profound contempt for this latest work." just makes me think you're pro-medication? Just a wild guess. Nothing wrong with that, it just suggests a bias.
I *revealed* bias. I am pro-science. Your "wild guess" is completely off the mark.
Lar
Posted by chumbawumba on May 11, 2009, at 20:30:46
In reply to Re: Antidepressants Hardly Help ( Time Magazine) » chumbawumba, posted by Larry Hoover on May 11, 2009, at 20:22:53
Well science is unemotional , contempt is not.
Posted by Larry Hoover on May 11, 2009, at 20:56:40
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by chumbawumba on May 11, 2009, at 19:10:06
> The phrase "I have profound contempt for this latest work." just makes me think you're pro-medication? Just a wild guess. Nothing wrong with that, it just suggests a bias.
Well, here's another in a lengthy thread on the subject.
https://www.dr-bob.org/babble/20080420/msgs/824891.htmlI have contempt for "scientists" who resort to deception in furtherance of an argument that has no factual basis. His paper was political, not scientific.
For example, the HAM-D is not an interval scale, it is ordinal. It is inappropriate to submit HAM-D scores to the statistical methods employed by Kirsch.
From another post I made, I quoted from other scientists' criticisms of the paper:
(Me)Well, let's see what his peers have said, shall we? From the reviews appended to the original article, and BMJ:
"In conclusion, the paper of Kirsch and his colleagues presents nothing that was not previously known, but it does introduce empirically unsupported conclusions and erroneous interpretation that are potentially misleading."
(Me) Oh, I said the same things in my critique.
"Among other things, these applications have revealed that the misuse of ordinal scaled data can produce erroneous data and drive inaccurate conclusions. Consequently, concerns must be raised over the accuracy of the results of the meta-regression performed by Kirsch et al, given they have undertaken sophisticated mathematical operations on data which do not support such activities. Moreover, it is worth noting that even the calculation of a mean, a standard deviation, and a change score are invalid on ordinal data, given that these all assume equal interval scaling."
(Me) Translation: The statistical methods applied during the meta-analysis (of the ordinal Hamilton Depression Scale scores) are not meaningful. Ergo, any conclusions therefrom suffer from the same limitation.
"In each case the null hypothesis that the Kirsch et al estimator is unbiased has been tested and overwhelmingly rejected."
(Me)Re-analysis of Kirsch's methods demonstrate that his methodology negatively biased the outcomes.
(Me)And, even if one accepts the premise that these data are analyzable via this methodolgy, a recalculation under more rigorous procedures provides this outcome:
"If the weighted mean difference is used (an equally, or more valid approach given that all studies utilised the same outcome measure, namely the HRSD) effect sizes expressed in HRSD scores are larger than reported in this study (2.8 vs 1.8), and paroxetine and venlafaxine reach the NICE criteria for 'clinical significance' (HRSD change > 3)."
(Me)Aside, I had estimated the effect size plotted on Table 4 at about d=3, so I feel validated that my common-sensical critical-thinking test of Kirsch's stats is supported mathematically.
Regards,
Lar
Posted by Larry Hoover on May 11, 2009, at 20:57:44
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by chumbawumba on May 11, 2009, at 20:30:46
> Well science is unemotional , contempt is not.
You are right, contempt is personal. Does that somehow invalidate my arguments?
Lar
Posted by chumbawumba on May 11, 2009, at 21:11:40
In reply to Re: Antidepressants Hardly Help ( Time Magazine) » chumbawumba, posted by Larry Hoover on May 11, 2009, at 20:57:44
> > Well science is unemotional , contempt is not.
>
> You are right, contempt is personal. Does that somehow invalidate my arguments?
>
> LarNo not at all. Also I happen to agree that medications can be very helpful.
But you have invested a fair amount of time in critiqueing this particular study. It just seems like you've taken a side pretty passionately.
Posted by Larry Hoover on May 11, 2009, at 21:19:40
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by chumbawumba on May 11, 2009, at 21:11:40
> > > Well science is unemotional , contempt is not.
> >
> > You are right, contempt is personal. Does that somehow invalidate my arguments?
> >
> > Lar
>
> No not at all. Also I happen to agree that medications can be very helpful.I wish they had been for me, but my negative experiences are anecdotal.
> But you have invested a fair amount of time in critiqueing this particular study. It just seems like you've taken a side pretty passionately.
Indicating why a political treatise masquerading as science is false can require some effort.
Lar
Posted by sowhysosad on May 11, 2009, at 21:37:29
In reply to Re: Antidepressants Hardly Help ?????????, posted by SLS on May 11, 2009, at 5:56:32
> These drugs work. It seems misanthropic to me that certain people should set out to prove otherwise.
Too right. The traditionalist right-wing tabloid press over here (the UK) has an agenda to discredit modern AD's which just seems like sheer malevolence.
Or perhaps they think that treating a mental illness is somehow "un-British". "Stiff upper lip" and all that ****. After all, they wouldn't try to discredit chemotherapy or insulin. (Mind you, they have printed mounds of unexpurgated, unscientific crap trying to link autism to the MMR vaccine, which has directly caused record levels of measles cases.)
Why don't they just **** off and let us take our meds in peace?
Posted by Sigismund on May 11, 2009, at 21:47:34
In reply to Re: Antidepressants Hardly Help ?????????, posted by sowhysosad on May 11, 2009, at 21:37:29
>These drugs work. It seems misanthropic to me that certain people should set out to prove otherwise.
They work a bit but they don't work very well.
And if they work well they will likely be banned.
Posted by sowhysosad on May 11, 2009, at 21:50:45
In reply to Re: Antidepressants Hardly Help ?????????, posted by sowhysosad on May 11, 2009, at 21:37:29
It's also just occurred to me that perhaps some unsavoury hacks highlight these scientifically-bankrupt studies because they think they're being pioneering in exposing some "big lie" and revealing the "truth" about particular treatments.
That would explain why the MMR/autism nonsense still has legs in the UK years after the original research was debunked. In a journalist's mind, it's far more appealing to portray a useful and innocuous medical intervention as scary and sinister than it is to reflect actual science.
> > These drugs work. It seems misanthropic to me that certain people should set out to prove otherwise.
>
> Too right. The traditionalist right-wing tabloid press over here (the UK) has an agenda to discredit modern AD's which just seems like sheer malevolence.
>
> Or perhaps they think that treating a mental illness is somehow "un-British". "Stiff upper lip" and all that ****. After all, they wouldn't try to discredit chemotherapy or insulin. (Mind you, they have printed mounds of unexpurgated, unscientific crap trying to link autism to the MMR vaccine, which has directly caused record levels of measles cases.)
>
> Why don't they just **** off and let us take our meds in peace?
Posted by chumbawumba on May 11, 2009, at 22:13:18
In reply to Re: Antidepressants Hardly Help ( Time Magazine) » chumbawumba, posted by Larry Hoover on May 11, 2009, at 21:19:40
> Indicating why a political treatise masquerading as science is false can require some effort.
>
> Lar
>OK, I think somewhere I missed the point tremendously. I thought we were just talking about whether or not it was good science.
Why do you think this is a political treatise? Is it because the socialized medical system in Britain (and possibly soon the US) wouldn't have to pay for these drugs if they were discredited?
No wonder you're passionate if politics are involved :)
Posted by sowhysosad on May 11, 2009, at 22:18:11
In reply to Re: Antidepressants Hardly Help ?????????, posted by Sigismund on May 11, 2009, at 21:47:34
They've been almost entirely effective and tolerable for me on a number of occasions, and anecdotal evidence would suggest for many other people too. I don't think research reflects exactly how successful meds can be because of candidate selection issues outlined earlier in this thread.
Still, I appreciate that we probably all have subtly different underlying causes for our depression, so SSRI's will be useless for some.
> >These drugs work. It seems misanthropic to me that certain people should set out to prove otherwise.
>
> They work a bit but they don't work very well.
>
> And if they work well they will likely be banned.
Posted by SLS on May 11, 2009, at 22:25:58
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 11, 2009, at 16:47:28
> I think all depression is biological...Let us start at the beginning.
1. What is depression? How do you know it when you see it? What are YOUR criteria for identifying depression?
> in that a depressed persons brain is physically different
2. Is it your contention that every person that you identify as depressed according to the criteria you established in question number one demonstrates morphological, physiological, or genetic aberrations that can be measured and deemed to be pathological?
- Scott
Posted by chumbawumba on May 11, 2009, at 22:40:19
In reply to Re: Antidepressants Hardly Help ?????????, posted by SLS on May 11, 2009, at 22:25:58
>
> > I think all depression is biological...
>
> Let us start at the beginning.
>
> 1. What is depression? How do you know it when you see it? What are YOUR criteria for identifying depression?
>
> > in that a depressed persons brain is physically different
>
> 2. Is it your contention that every person that you identify as depressed according to the criteria you established in question number one demonstrates morphological, physiological, or genetic aberrations that can be measured and deemed to be pathological?
>
>
> - ScottYes. I contend that there is nothing in mind that does not have a biologic concomitant.
Posted by Larry Hoover on May 11, 2009, at 23:01:02
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by chumbawumba on May 11, 2009, at 22:13:18
It was not good science. That was the thrust of each of my arguments. I concluded the paper was shaped to a pre-existing viewpoint, rather than reaching conclusions derivative of the underlying science. Thus, I concluded that the article was political, as it was unscientific, in my considered opinion.
I've read many papers authored by Kirsch, and they all have a similar slant when discussing antidepressants.
His books deal with hypnosis and suggestibility. If only he would stick to what he knows best, rather than writing deceptively suggestive material to advance false premises.
I've read many of the original Phase III research studies (the raw data, hundreds of pages, not the published blurb) done by Glaxo for Paxil, and others for Effexor, and Prozac. A lot of that work was simply poorly done, conducted over 20 years ago, in the infancy of antidepressant clinical trials. To force the inclusion of poorly conducted studies in this meta-analysis confounds improper methodology with poor drug efficacy. Yet he forces inclusion of that data. Nonetheless, Kirsch himself found a highly significant benefit of antidepressants over placebo (p < .001), and his initial difference scores well exceeded the threshold for clinical significance of 0.50 (Table 2), but he spent many paragraphs finding a way to dismiss those findings by applying statistical methods that are simply inappropriate, and quoting statistics in the paper that are not found in his tables. His own methodology was fatally flawed, and even a simple viewing of his own charts falsifies the statistics he derived.
Honestly, had his science been sound, I've have supported his conclusions. I am pro-science, but I will independently form conclusions of just what that is. I am not pro-med, either. If the evidence is pro-med, then that is what I will report.
Lar
Posted by SLS on May 11, 2009, at 23:15:41
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 11, 2009, at 22:40:19
> > 2. Is it your contention that every person that you identify as depressed according to the criteria you established in question number one demonstrates morphological, physiological, or genetic aberrations that can be measured and deemed to be pathological?
> Yes. I contend that there is nothing in mind that does not have a biologic concomitant.
Pathological?
The first question was the more important of the two that I asked.
1. What is depression? How do you know it when you see it? What are YOUR criteria for identifying depression?
- Scott
Posted by chumbawumba on May 11, 2009, at 23:17:05
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 11, 2009, at 22:40:19
> >
> > > I think all depression is biological...
> >
> > Let us start at the beginning.
> >
> > 1. What is depression? How do you know it when you see it? What are YOUR criteria for identifying depression?
> >
> > > in that a depressed persons brain is physically different
> >
> > 2. Is it your contention that every person that you identify as depressed according to the criteria you established in question number one demonstrates morphological, physiological, or genetic aberrations that can be measured and deemed to be pathological?
> >
> >
> > - Scott
>
> Yes. I contend that there is nothing in mind that does not have a biologic concomitant.Regarding #1 I'd say the best criteria for diagnosing depression is just asking a person "Are you depressed?" Seriously. I mean you can go further and say do you feel hopeless, do you feel suicidal, but it all starts with "Are you depressed?"
And Regarding #2
Yes, I would say that most people if they were being truthful in answer to #1 would show brain differences.
Posted by SLS on May 11, 2009, at 23:28:18
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 11, 2009, at 23:17:05
> Regarding #1 I'd say the best criteria for diagnosing depression is just asking a person "Are you depressed?" Seriously. I mean you can go further and say do you feel hopeless, do you feel suicidal, but it all starts with "Are you depressed?"
I don't think it is prudent to ask the patient to provide their own diagnosis. When a person says to their doctor, "I feel weak", the doctor would be remiss in prescribing weight lifting as a remedy without investigating any further.
You still have not answered my question.
1. What is depression? How do you know it when you see it? What are YOUR criteria for identifying depression?
It is my contention that the state of the art of selecting patients suffering from major depressive disorder for clinical investigations of antidepressants is not much more sophisticated than the diagnostic method that you have suggested. You have just proved my point.
- Scott
Posted by SLS on May 11, 2009, at 23:36:21
In reply to Re: Antidepressants Hardly Help ????????? » chumbawumba, posted by SLS on May 11, 2009, at 23:28:18
> > Regarding #1
> You still have not answered my question.
>
> 1. What is depression? How do you know it when you see it? What are YOUR criteria for identifying depression?> > I'd say the best criteria for diagnosing depression is just asking a person "Are you depressed?" Seriously. I mean you can go further and say do you feel hopeless, do you feel suicidal, but it all starts with "Are you depressed?"
I apologize. I guess you really did answer my question to the best of your ability.
- Scott
Posted by chumbawumba on May 12, 2009, at 0:01:07
In reply to Re: Antidepressants Hardly Help ????????? » chumbawumba, posted by SLS on May 11, 2009, at 23:28:18
Well of course you ask some follow up questions. But my point is that the most sophisticated differential diagnosis is probably no better than asking someone how they are doing. If you think otherwise you've got a lot more faith in psychiatry than I do.
All the falderol of so called modern psychiatric diagnosis is just a bunch of guys who really don't know anything trying to sound like they do.
Again I go back to my statement: All phenomenon of mind have a bological concomitant, therefore all depression is biological.
But in the end what if you do manage to cobble together a study with participants that comprise a particular genotype. Some subtype of depression with a clear genetic etiology what have you proved? That's like studying albinos in an investigation of skin cancer treatments. You'll be able cure almost nobody 100% of the time.
Posted by SLS on May 12, 2009, at 0:06:35
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 12, 2009, at 0:01:07
> Again I go back to my statement: All phenomenon of mind have a bological concomitant, therefore all depression is biological.
We all know that the mind is a manifestation of the brain. This is not a point of contention. However, you still have not addressed the issue of pathology.
- Scott
Posted by SLS on May 12, 2009, at 0:26:33
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 12, 2009, at 0:01:07
> Well of course you ask some follow up questions.
Only the same two - over and over.
> But my point is that the most sophisticated differential diagnosis is probably no better than asking someone how they are doing.
Again, you have very eloquently proved my point. Thanks.
> If you think otherwise you've got a lot more faith in psychiatry than I do.
Perhaps not.
I have more faith in the lengthy psychometric examinations more often employed by psychologists than I do in the primitive 17 question rating scales employed by psychiatric clinical investigators.
> All the falderol of so called modern psychiatric diagnosis is just a bunch of guys who really don't know anything trying to sound like they do.
Thanks again.
> Again I go back to my statement: All phenomenon of mind have a bological concomitant, therefore all depression is biological.
As I have so accurately said before, "The brain determines the mind as the mind sculpts the brain." You are not saying anything new here. However, you still avoid the concept of pathology. Depressed mood is perfectly healthy when it is not a symptom of a biological pathology. It is integral to our experiences in an environment containing psychosocial stresses. It can be both protective and instructive.
> But in the end what if you do manage to cobble together a study with participants that comprise a particular genotype.
I believe you presume more understanding of affective disorders than what currently exists in the field of neuroscience. There are some associations between certain alleles and major depressive disorder (MDD), but we are looking at a multi-gene disorder that is influenced by epigenetic variables. The phenomenology of affective disorders is not as simple as you depict here.
- Scott
Posted by SLS on May 12, 2009, at 0:33:43
In reply to Re: Antidepressants Hardly Help ????????? » chumbawumba, posted by SLS on May 12, 2009, at 0:26:33
> Depressed mood is perfectly healthy when it is not a symptom of a biological pathology.
I should like to modify my statement here. There are many psychological pathologies that can produce chronic depression. This is not healthy. These are probably best treated psychologically, although antidepressants might still have utility in these cases.
- Scott
Posted by chumbawumba on May 12, 2009, at 0:48:57
In reply to Re: Antidepressants Hardly Help ????????? » chumbawumba, posted by SLS on May 12, 2009, at 0:06:35
Of course, biological processes are amenable to measurement. Pathological or not. And since all depression is a pathology that is a phenomenon of mind which manifests biologically it too can be measured. I suspect some people with longer term untreated depression would show anatomic changes whereas in others the differences would only be visible as fMRI or PET hotspots and cold spots.
I also suspect as the technology improves more will be learned about the differences between normal and depressed brain functioning. And if we look closely enough I'll bet we'll even be able to track in real time the changes in the brain as a person has a "hopeless thought" versus a "hopeful though". I don't think we're there yet.
It is well known that there is an interaction between the environment and the genetic code, feedback loops that control gene expression. For example the transcription of the gene which codes for lactase being turned on and off by the presence of lactose. I suspect there are many feedback loops at play in depression involving stress hormones and gene expression. Many things we do not understand quite yet but either can be measured or will lend themselves to measurement as the technology improves.
Perhaps it will even be possible to identify depressive subtypes. I suspect very strongly though that it won't break down into neat catgories like Major Depression, Dythymia, and Depressive personality disorder.
Nevertheless, I think all that will be very educational. But the first step is always the patient. "How you doing? How are you feeling? Are you depressed. Do you feel hopeless, do you want to die?" I think this is probably about the best we've got, and probably just as good an indicator that something is awry as anything else.
Posted by chumbawumba on May 12, 2009, at 0:56:44
In reply to Re: Antidepressants Hardly Help ?????????, posted by SLS on May 12, 2009, at 0:33:43
>I contend that these subpopulations DO NOT suffer from having a biological illness that should be the target of these investigations.
So are you backpedaling now on this statement. I think we've established that all depression is biological.
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