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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 29 to 53 of 75. Go back in thread:
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.
Posted by chumbawumba on May 12, 2009, at 1:46:50
In reply to Re: Antidepressants Hardly Help ????????? » chumbawumba, posted by SLS on May 12, 2009, at 0:26:33
What does it really matter if you give a really detailed psychometric intrument to people. Lets say you give them the MMPI, which I think is the most researched psychometric intrument on the planet. And you look at the Depression and Mania subscales. And a person comes out with an 80 T score on the former and a 20 T score on the latter. That's three standard deviations from the mean on both. That would be highly indicative of depression.
What have you proved? Essentially you have shown that this person has a similar profile as other people who had been somehow magically determined to be truly depressed whose answers were therefore suitable for to be used in the construction of the MMPI subscales. Thus the "empirical basis" of the MMPI. Fine, essentially you've shown that people who fall into some category called "Depression" give similar answers on a test. There is nothing in this that would suggest people who match this profile have a more "biologically based" illness. And that's the state of the art, the most widely researched psychometric intrument on the planet with over 500 questions is basically telling you that birds of a feather flock together. And maybe some information like atypical features, or psychotic. But again there is nothing here that would inform a selection criteria for a clinical study vis a vis "biologically based" depression (which it all is anyway).
So why not just ask "How are you doing?"
Posted by SLS on May 12, 2009, at 6:10:19
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 12, 2009, at 0:48:57
> Of course, biological processes are amenable to measurement. Pathological or not.
So... When does a depression become pathological?
> And since all depression is a pathology
Here, I disagree with you. You believe that depression is an answer to a single question. I believe it is a pathological phenomenon with specific symptom clusters.
Let us start at the beginning, again.
This time, I will state that the majority of clinical investigations of antidepressants are established to study major depressive disorder (MDD) - a phenomenon that is defined in the study and practice of medicine and using a set of observations of symptom clusters to aid in diagnoses. If it is the criterion that one be suffering from MDD to enter a study, why do you continue to see homogeneity when it is heterogeneity that confounds the selection process in the first place?
If you were responsible for the inclusion and exclusion of subjects in a study of MDD specifically, how would you go about it?
> I suspect some people with longer term untreated depression would show anatomic changes whereas
Even if they are treated.
> in others the differences would only be visible as fMRI or PET hotspots and cold spots.
Out of curiosity, do you feel that this is a trait or state specific finding?
> I also suspect as the technology improves more will be learned about the differences between normal and depressed brain functioning.
I am afraid that the technology has already determined that there are differences between people with MDD versus those without it. Among those without it are people who are depressed for one reason or another, but do not qualify as having this biological disorder.
> 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.Already been done. Even the presentation of different facial expressions produces measurable differences on PET and SPECT imaging studies. Not only that, but, most importantly, there is a difference between MDD versus non-MDD responses to the same stimuli.
> It is well known that there is an interaction between the environment and the genetic code
Yes, it is well known, along with much else that you have mentioned subsequently, so why bring it up when we are talking about the criteria and selection process for clinical investigations involving affective disorders?
- Scott
Posted by SLS on May 12, 2009, at 6:18:18
In reply to Re: Antidepressants Hardly Help ?????????, posted by chumbawumba on May 12, 2009, at 1:46:50
> What does it really matter if you give a really detailed psychometric intrument to people.
Because it works.
> Lets say you give them the MMPI...
Yes. This inventory is so complete, that it can even detect when someone is feigning depression.
http://asm.sagepub.com/cgi/content/abstract/7/1/55
> So why not just ask "How are you doing?"
I'm doing fine. I'm not in remission from bipolar depression, nonetheless, this is my answer to the question if you were to ask me right now. It isn't such a bad day for me today.
Where do we go from there...
By the way, how are YOU doing?
- Scott
Posted by SLS on May 12, 2009, at 8:36:17
In reply to Re: Antidepressants Hardly Help ????????? » chumbawumba, posted by SLS on May 12, 2009, at 6:10:19
We are getting closer...
http://www.ncbi.nlm.nih.gov/pubmed/19358877
1: Neuroscience. 2009 Apr 7. [Epub ahead of print]Click here to read Links
Imaging phenotypes of major depressive disorder: genetic correlates.
Savitz JB, Drevets WC.Mood and Anxiety Disorders Program, NIH/NIMH, B15K, North Drive, Bethesda, MD 20892, USA.
Imaging techniques are a potentially powerful method of identifying phenotypes that are associated with, or are indicative of, a vulnerability to developing major depressive disorder (MDD). Here we identify seven promising MDD-associated traits identified by magnetic resonance imaging (MRI) or positron emission tomography (PET). We evaluate whether these traits are state-independent, heritable endophenotypes, or state-dependent phenotypes that may be useful markers of treatment efficacy. In MDD, increased activity of the amygdala in response to negative stimuli appears to be a mood-congruent phenomenon, and is likely moderated by the 5-HT transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR). Hippocampal volume loss is characteristic of elderly or chronically-ill samples and may be impacted by the val66met brain-derived neurotrophic factor (BDNF) gene variant and the 5-HTTLPR SLC6A4 polymorphism. White matter pathology is salient in elderly MDD cohorts but is associated with cerebrovascular disease, and is unlikely to be a useful marker of a latent MDD diathesis. Increased blood flow or metabolism of the subgenual anterior cingulate cortex (sgACC), together with gray matter volume loss in this region, is a well-replicated finding in MDD. An attenuation of the usual pattern of fronto-limbic connectivity, particularly a decreased temporal correlation in amygdala-anterior cingulate cortex (ACC) activity, is another MDD-associated trait. Concerning neuroreceptor PET imaging, decreased 5-HT(1A) binding potential in the raphe, medial temporal lobe, and medial prefrontal cortex (mPFC) has been strongly associated with MDD, and may be impacted by a functional single nucleotide polymorphism in the promoter region of the 5-HT(1A) gene (HTR1A: -1019 C/G; rs6295). Potentially indicative of inter-study variation in MDD etiology or mood state, both increased and decreased binding potential of the 5-HT transporter has been reported. Challenges facing the field include the problem of phenotypic and etiological heterogeneity, technological limitations, the confounding effects of medication, and non-disease related inter-individual variation in brain morphology and function. Further advances are likely as epigenetic, copy-number variant, gene-gene interaction, and genome-wide association (GWA) approaches are brought to bear on imaging data.
PMID: 19358877 [PubMed - as supplied by publisher]
Posted by Garnet71 on May 12, 2009, at 11:02:18
In reply to Antidepressants Hardly Help ( Time Magazine), posted by rvanson on May 10, 2009, at 23:31:50
I have come across a few study of studies. This article points to studies conducted by the drug companies themselves--studies that showed ADs were not much more effective than placebos (and leaving the political Kirsch guy out of it).
http://www.nytimes.com/2008/01/17/health/17depress.html?_r=1
The makers of antidepressants like Prozac and Paxil never published the results of about a third of the drug trials that they conducted to win government approval, misleading doctors and consumers about the drugs true effectiveness, a new analysis has found.
In published trials, about 60 percent of people taking the drugs report significant relief from depression, compared with roughly 40 percent of those on placebo pills. But when the less positive, unpublished trials are included, the advantage shrinks: the drugs outperform placebos, but by a modest margin, concludes the new report, which appears Thursday in The New England Journal of Medicine.
Previous research had found a similar bias toward reporting positive results for a variety of medications; and many researchers have questioned the reported effectiveness of antidepressants. But the new analysis, reviewing data from 74 trials involving 12 drugs, is the most thorough to date. And it documents a large difference: while 94 percent of the positive studies found their way into print, just 14 percent of those with disappointing or uncertain results did....
Posted by Garnet71 on May 12, 2009, at 11:06:37
In reply to Antidepressants Hardly Help ( Time Magazine), posted by rvanson on May 10, 2009, at 23:31:50
Antidepressant drug trials turn away most of the depressed population
http://www.brown.edu/Administration/News_Bureau/2001-02/01-091.html
Studies establishing the effectiveness of antidepressants are based on highly selective samples of depressed patients. New research by Brown University psychiatrists found as many as 85 percent of depressed patients treated in an outpatient setting would be excluded from the typical study to determine whether an antidepressant works.
--------------------------------------------------------------------------------PROVIDENCE, R.I. While antidepressants are among the most frequently prescribed medications, most patients treated for major depression in a typical outpatient psychiatric practice would not qualify to take part in a clinical trial for a new antidepressant drug, according to a new Brown University study.
Trials to determine the effectiveness of antidepressants have historically evaluated only a small subset of depressed individuals with a very specific clinical profile. People diagnosed with other psychiatric problems and people with mild depression are among those excluded, says the study, which appears in the March 2002 American Journal of Psychiatry....
Posted by SLS on May 12, 2009, at 11:53:24
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by Garnet71 on May 12, 2009, at 11:06:37
> Antidepressant drug trials turn away most of the depressed population
>
> http://www.brown.edu/Administration/News_Bureau/2001-02/01-091.html
>
> Studies establishing the effectiveness of antidepressants are based on highly selective samples of depressed patients. New research by Brown University psychiatrists found as many as 85 percent of depressed patients treated in an outpatient setting would be excluded from the typical study to determine whether an antidepressant works.
>
>
> --------------------------------------------------------------------------------
>
> PROVIDENCE, R.I. While antidepressants are among the most frequently prescribed medications, most patients treated for major depression in a typical outpatient psychiatric practice would not qualify to take part in a clinical trial for a new antidepressant drug, according to a new Brown University study.
>
> Trials to determine the effectiveness of antidepressants have historically evaluated only a small subset of depressed individuals with a very specific clinical profile. People diagnosed with other psychiatric problems and people with mild depression are among those excluded, says the study, which appears in the March 2002 American Journal of Psychiatry....
Does there appear anywhere in these information sources exactly why the selection process exists and what are the criteria used?
- Scott
Posted by SLS on May 12, 2009, at 12:13:23
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by SLS on May 12, 2009, at 11:53:24
I apologize. I see that the article does provide some important information regarding selection criteria. However, it would be nice to interview a series of clinical investigators or the FDA as to why these criteria remain in place, even though it is my contention that in real life, such screening processes are not employed strictly enough.
When you want to find out if a drug will treat a disease, you need to be sure that the subjects you select have the disease in the first place. For now, the exclusive selection criteria are the best these studies have come up with to help insure a valid study population. There is no biological test that a consensus of researchers has determined is specific enough to effectively identify MDD. Not yet. Soon. In the meantime, it is easier to use symptom severity as a guideline to choose subjects.
- Scott
Posted by Larry Hoover on May 12, 2009, at 12:21:14
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by Garnet71 on May 12, 2009, at 11:02:18
The NYT article contains an error that distorts the article. It says "94 percent of the positive studies found their way into print, just 14 percent of those with disappointing or uncertain results did..." In fact, 39% of the latter group found their way into print, and others were included in articles that covered more than one study.
In any case, the drug companies don't publish results. Independent journals do, or don't, as they choose. Surely, articles with significant findings have much better chance at finding their way into print, with that decision subject entirely at the discretion of third-party editors and reviewers. Who would read a journal with inconclusive studies being reported?
In fact, the authors of the NEJM review identified that limiting qualifier in the opening sentence of the 'Conclusions' section of their abstract, but I didn't see it reproduced in any lay press article. It said: "We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both."
http://content.nejm.org/cgi/content/full/358/3/252
If that criterion could not be determined, then what right have they (the New York Times) to lay the blame on the pharmaceutical companies? Maybe they themselves can't read. Or maybe they themselves have a publishing bias.
In any case, the FDA saw all the studies. The drugs were approved on the basis of fully disclosed clinical trial results.
Lar
Posted by Larry Hoover on May 12, 2009, at 12:25:47
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by Garnet71 on May 12, 2009, at 11:06:37
"New research by Brown University psychiatrists found as many as 85 percent of depressed patients treated in an outpatient setting would be excluded from the typical study to determine whether an antidepressant works."
The exclusion criteria are set by bodies entirely independent of the pharmaceutical companies, in order to provide the most clear-cut evidence for or against efficacy. Exclusion criteria are to minimize confounds. There's nothing sinister about it.
Lar
Posted by SLS on May 12, 2009, at 12:58:38
In reply to Re: Antidepressants Hardly Help ( Time Magazine) » SLS, posted by SLS on May 12, 2009, at 12:13:23
It is instructive to follow the URL links provided in the bibliography. The citations offered are worth reading closely. That is all I would like to say at this time.
- Scott
Posted by SLS on May 12, 2009, at 13:09:22
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by SLS on May 12, 2009, at 12:58:38
> It is instructive to follow the URL links provided in the bibliography. The citations offered are worth reading closely. That is all I would like to say at this time.
I apologize. That is not a very respectable way to engage in a debate. I guess I should actually cite the citations that I found contradictory to the thesis of the NYT article or the others I found that were fraught with their own biases. Maybe later. I have to spend the rest of the day studying for a final exam at school.
Have a nice day, folks.
- Scott
Posted by Garnet71 on May 12, 2009, at 13:49:06
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by SLS on May 12, 2009, at 13:09:22
You guys are making me laugh! I just want you all to analyze the methodologies of the pro-drug studies as much as you analyze the methodologies of the anti-drug studies. Unless for some mysterious reason, you think there is bias on ONLY the one side. 8| Now that would be silly.
If you do this, then I'll pretty much be satisfied with whatever you all think :-)
I've been following this whole thread while on hold during all the personal business calls I've been making over the past 2 days, in between classes; I actually don't have time to read the links and citations! ..but it seems to me some of you ENJOY reading them....an analyzing all this stuff..so I thought I'd leave that up to you while I analyze all my homework assignments..lol.
Posted by Larry Hoover on May 12, 2009, at 14:08:24
In reply to Re: Antidepressants Hardly Help ( Time Magazine), posted by Garnet71 on May 12, 2009, at 13:49:06
> I just want you all to analyze the methodologies of the pro-drug studies as much as you analyze the methodologies of the anti-drug studies.
I have, and I do.
If conclusions are not supported by the evidence, in my opinion, I make a statement about it. The topic happens to be anti-drug bias at the moment, is all.
If you think there is something wrong with my analysis, then I'm happy to listen to other viewpoints. I learn best from my mistakes.
Lar
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Dr. Bob is Robert Hsiung, MD,
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