![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 70 to 94 of 143. Go back in thread:
Posted by Squiggles on May 12, 2006, at 15:30:44
In reply to Re: Statistical question on SSRIs, posted by genes-r-us on May 11, 2006, at 12:35:11
> Hi, first time poster here. Well, I just wrote a reasonably long and (hopefully) informative post on what happened between Dr. Healy and the University of Toronto, but the post submission process ate it, and I don't have the energy to re-do the whole thing from scratch.I hope you find time to repost it - it would
be interesting to read from a new poster.
Suffice it to say that Dr. Healy was given a formal offer of a position at a University of Toronto associated centre, made his infamous comments in an introductory lecture, and was promptly relieved of his emplyoment offer.It does appear that there are certain links
missing to the public and maybe the court.
Was it the content that was threatening to
the product Prozac (Healy says U of T knew
of his opinions beforehand); or was it his
"worldview" which disturbed them or made them
see him in a new light? Or was it possibly an
agreement he made with the U of T, which he
broke in his speech? We don't know. At least,
I don't know.Eli Lilly, by the way, appears to have been the largest outside source of funding for the centre at the time this all happened (and may still well be).
That's irrelevant. You may as well say that
so and so slept with a colleague. Furthermore,
there is no evidence that Eli Lilly played a role, nor that is a conspiracy theory came true, and
the "truth" was revealed, that Eli Lilly's stock
would suffer any substantial damage, great enough to take action against the hiring of a radical
professor. Though, i can understand that the
infamous corridor floating around the net
cooler may make people believe Lilly had a role.So one can't use the fact that he was stripped of his position as a factor when considering the validity of his views on this issue, much as it's not particularly informative to define a word using the word itself in the definition.
I don't understand the above paragraph.
Squiggles
Posted by Squiggles on May 12, 2006, at 17:26:38
In reply to Re: Statistical question on SSRIs - Final Verdict » genes-r-us, posted by Squiggles on May 12, 2006, at 15:30:44
SORRY - some of my paragraphs here are sloppy;
i have been having some trouble with my memory
since my last med misadventure; i will make
some corrections.
> > Hi, first time poster here. Well, I just wrote a reasonably long and (hopefully) informative post on what happened between Dr. Healy and the University of Toronto, but the post submission process ate it, and I don't have the energy to re-do the whole thing from scratch.
>
*I hope you find time to repost it - it would
be interesting to read from a new poster.
>
>
> Suffice it to say that Dr. Healy was given a formal offer of a position at a University of Toronto associated centre, made his infamous comments in an introductory lecture, and was promptly relieved of his emplyoment offer.
>
*It does appear that there are certain links
missing to the public and maybe the court.
Was it the content that was threatening to
the product Prozac (Healy says U of T knew
of his opinions beforehand); or was it his
"worldview" which disturbed them or made them
see him in a new light? Or was it possibly an
agreement he made with the U of T, which he
broke in his speech? We don't know. At least,
I don't know.
>
>
>
> Eli Lilly, by the way, appears to have been the largest outside source of funding for the centre at the time this all happened (and may still well be).
>
*That's irrelevant. You may as well say that
so and so slept with someone who was the
most influential colleague in the department. Furthermore, there is no evidence that Eli Lilly played a role in Healy's or the university's actions. Nor that, as a conspiracy theory might have it and even come true, that Eli Lilly twisted the university's arm. It is unlikely that Eli Lilly's stock would suffer any substantial damage, great enough to take action against the hiring of a radical professor. They are powerful and rich enough to afford many gaflies and radical professors in universities who criticize their products. Though, i can understand that the
infamous gossiped corridor confrontation (floating around the net ether) about Dr. Nemeroff and Dr. Healy coming to near blows may make people believe Lilly had a role.
>
> So one can't use the fact that he was stripped of his position as a factor when considering the validity of his views on this issue, much as it's not particularly informative to define a word using the word itself in the definition.
>
*I don't understand the above paragraph.
>
*Squiggles
>
>
Posted by Squiggles on May 12, 2006, at 20:35:19
In reply to Re: Statistical question on SSRIs - Final Verdict » Squiggles, posted by Squiggles on May 12, 2006, at 17:26:38
IMPORTANT ADDENDUM:
I just found an important paper:
Please see p. 200 of this document
for Dr. Nemeroff's defense:http://www.fda.gov/ohrms/dockets/ac/prozac/2443T1.PDF
-----------
Squiggles
Posted by Larry Hoover on May 12, 2006, at 22:57:28
In reply to Re: Statistical question on SSRIs - ADDENDUM, posted by Squiggles on May 12, 2006, at 20:35:19
> IMPORTANT ADDENDUM:
>
> I just found an important paper:
>
> Please see p. 200 of this document
> for Dr. Nemeroff's defense:
>
> http://www.fda.gov/ohrms/dockets/ac/prozac/2443T1.PDF
>
> -----------
>
> SquigglesDefense? I don't even know why you used that word, in this context. Why don't you give a brief statement, in your own words, what you think is being presented at that point in the document?
Lar
Posted by Squiggles on May 13, 2006, at 3:11:59
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Larry Hoover on May 12, 2006, at 22:57:28
> > IMPORTANT ADDENDUM:
> >
> > I just found an important paper:
> >
> > Please see p. 200 of this document
> > for Dr. Nemeroff's defense:
> >
> > http://www.fda.gov/ohrms/dockets/ac/prozac/2443T1.PDF
> >
> > -----------
> >
> > Squiggles
>
> Defense? I don't even know why you used that word, in this context. Why don't you give a brief statement, in your own words, what you think is being presented at that point in the document?
>
> LarI will, give me some time. I'd like to read the
whole thing.Squiggles
Posted by Larry Hoover on May 13, 2006, at 8:35:14
In reply to Re: Statistical question on SSRIs - ADDENDUM » Larry Hoover, posted by Squiggles on May 13, 2006, at 3:11:59
> > Defense? I don't even know why you used that word, in this context. Why don't you give a brief statement, in your own words, what you think is being presented at that point in the document?
> >
> > Lar
>
> I will, give me some time. I'd like to read the
> whole thing.
>
> SquigglesI'm perennially confounded in conversations with you, my friend. We are so different in style. I should not have used the word defense without having read the paper. How do you know it's an important paper?
All I saw at pp. 200 and onwards was a very concise and precise definition of the role of anecdote in scientific inquiry. An extremely limited role, which upon revelation seems to raise the hackles of non-scientists. I struggle against it, here, myself. The hackle-raising, I mean. His example re: tonsils and tonsillectomy, is an excellent one.
Lar
Posted by Squiggles on May 13, 2006, at 9:59:43
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Larry Hoover on May 13, 2006, at 8:35:14
Please be patient - I am reading it now.
It's important because so many scientists
and lawyers and victims are giving testimony
before the FDA and at an early period of the
drug's development.As far Dr. Nemeroff is concerned, his
contention that "testimonials" and "anecdotes"
are not scientifically significant, is not
a strange idea in statistical validity. But I
see some counterexamples by Fitz which i will
go into later.As for depression and its suicidality, and
a causal relation, imho this does not exclude
the possibility of suicidality in drug withdrawal,
inappropriate drug, e.g. Prozac or ther conditions. There is one thing he says, which
makes sense - two things can be true and not
be related.You sound like you've been through this really
fascinating stage in the (hopefully) evolution of
psychopharmacology, but I am just a layman.Still reading - back when I'm done with any comments. Hope others find it interesting too.
Squiggles
> I'm perennially confounded in conversations with you, my friend. We are so different in style. I should not have used the word defense without having read the paper. How do you know it's an important paper?
>
> All I saw at pp. 200 and onwards was a very concise and precise definition of the role of anecdote in scientific inquiry. An extremely limited role, which upon revelation seems to raise the hackles of non-scientists. I struggle against it, here, myself. The hackle-raising, I mean. His example re: tonsils and tonsillectomy, is an excellent one.
>
> Lar
>
Posted by Squiggles on May 13, 2006, at 19:09:46
In reply to Re: Statistical question on SSRIs - ADDENDUM » Larry Hoover, posted by Squiggles on May 13, 2006, at 9:59:43
Preliminary remarks:
I am still reading this 400-plus page
FDA document. I confess, it is as
riveting as "Inherit the Wind".My computer is covered with notes, which
I hope to allude to in a discussion later.Here is my initial response, in case you
are reading this thread:1. I am surprised by the lack of curiousity
in medicine for individual cases regarding
why some people took Prozac and then killed themselves. Some of the big guns seem to be satisfied with statistical data as an explanation. And I suppose if the question is why 4 million others did not commit suicide, statistics is relevant the validity of the suicidality propabability. Or that depression in itself carries with it that risk - but that is obvious. People would not take antidepressants if they were not depressed in the first place, and they must have been alive when taking them.The question that I have not seen (with the exception of the Bulimia case), in these really tragic, gruesome, horrible cases presented here by an admittedly mostly biased group -- the question i have not seen raised is DID ANY OF THESE PEOPLE STOP, INTERRUPT, OR SKIP a PROZAC pill? I bring this up because my personal experience has been that akathisia (which really looks more like MANIA in these cases) is almost inevitable with ANY AD or benzodiazepine when stopping the drug or reducing the dose too fast. That I think would provide an explanation - a medical explanation based on how the body reacts given that all these bodies were more or less the same -- a contention that was not studied but by Dr. Nemeroff presumed not to be the case (i.e. with his introduction of extraneous factors such as "multiple personality disorder", "frontal lobe epilepsy", etc. Alternatively, some other explanation (e.g. Dr. Sheldon Preskorn talking about the lack of some
enzyme in some people rather than others) might explain the metabolism of a drug. Someting specific like that, i think would be more satisfactory that a smorgasbord offer of various conditions that may or may not affect how people respond to a certain drug. After all, the point here is that Prozac more likely than other drugs (I believe Dennis Clarke said that the FDA documented 500 cases of suicide, which 10-20 times that of the FDA's history).2. Rosedale (around p. 90) seems to insinuate that Scientologists somehow had something to do with the Prozac-induced reactions. But no evidence is offered for this presumption. I find this disturbing and curious.
That's all for now.
Squiggles
Posted by linkadge on May 14, 2006, at 1:26:14
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Squiggles on May 13, 2006, at 19:09:46
I read a few studies suggesting that people with the SS varients of the serotonin transporter may react to fluoxetine or other SSRI's with more anxiety, akathesia, agitation, and insomnia then people with longer varients.
The same thing goes with stimulants. One kid can take ritalin and it calms him down while another can take it and feel very agitated and paranoid.Is it the drug that caused the suicides? Absolutely, in my opinion. In some of these cases, had the drug not been introduced, lives may not have been lost. But, I do think that there may be genetic predispositions to SSRI induced akathesia and suicidal behavior that do not fall under the category of "latent bipolar".
So, perhaps the drug should not be banned completely, but there should be adequate warning that the drug has the potential. There should also be continued investigation into the potential mechanisms.
I've heard of people feeling acutely suicidal after taking antipsychotics. Some antipsychotics will block dopamine reception in the pleasure centres of the brain.
An SSRI too will decrease dopamine release in the neucleus accumbens via agonism at 5-ht2c. So you may have an acute dysphoria, and akathesia, in a perhaps already suicidal person.
Linkadge
Posted by Squiggles on May 14, 2006, at 9:42:48
In reply to Re: Statistical question on SSRIs - ADDENDUM, posted by linkadge on May 14, 2006, at 1:26:14
I have often read of how different
people have different reactions to
drugs. For example, this is the case
with people from different gene pools.
Oriental people react to alcohol more
adversely, as do Native Indians.
Thallasimia is common in Meditterranean
Eastern European people. In
a mixed gene pool, though I don't think
it's as prevalent.I'm still reading and have come to Dr.
Casper's questions about monitoring of the
drug and knowledge of plasma level. I think
these are important questions, and do not
exclude necessarily the idiosyncratic
predisposition of the person taking the
drug. Dr. Teicher also gives attention to
the individual's response to fluoxetine.Squiggles
Posted by Squiggles on May 14, 2006, at 15:06:42
In reply to Re: Statistical question on SSRIs - ADDENDUM » linkadge, posted by Squiggles on May 14, 2006, at 9:42:48
Notes:
- I finished giving it a cursory read - it is
actually only 342 pages;- at the end of the day, labelling is considered
a good thing by the committee, regardless of the
0 vote on the proposition that fluoxetine (and other ADs) can cause suicidality; what are we
to make of that? I would say, that labelling or not labelling is inconsequential and a token which the FDA can take and do with as it pleases. It will probably make little of a dent to Eli Lilly or any other big drug company. Furthermore, to relieve the drug company of any responsibilty of what is overtly agreed a dangerous side effect (i.e. suicidality), the committee proposes that patients and the FDA might write a "Dear Doctor" letter to the physicians discussing the resolutions. Dr. Mann thinks that even this is going too far.- personal points of interest: the "roll-back phenomenon" - that has been my speculation about how an AD and in particular ADs that are ennervating or agitating, can precipiate severe anxiety in the midst of depression, after taking it. This condition might drive a depressed, and
stuporous melancholic to actually get the energy to finally end his misery through suicide.Apparently, this scenario is known from clinical circles as the "roll-back phenomenon" and it is not unique to Prozac. But it is not something that is given great heed in this hearing. I think the most salient causal factor for most seems to be "depression" - that depression carries with it the risk of suicide. A comparison between "suicide from depression" and "suicide after, between, during, of the drug taking" is not compared to my knowledge.
- personal point of interest: the description of the headaches: their severity and back of the head splitting sensation, and severe illness following; that is familiar to me: with clonazepam withdrawal; i was sick for a month and I think i had a seizure, brain haemorrhage or stroke; like the person describing this on Prozac, it was very hard to even move your head, and it felt like dying -- is it possible that the plasma level fluctuated on account of not taking Prozac every day as prescribed? Was there withdrawal? Is hyperthermia something that can affect the brain in drug treatment? Medical questions are surprisingly few in comparison to statistical proofs.
The dr. monitoring or lack of it, is brought up and there is some talk of how appalling physician care is in some cases. I would say that in such cases, I would agree with Dr. Torrey -- we need more clinics and more care, not more labelling and "Dear Doctor letters" from drug companies. Also, if there is such dearth of monitoring, it may actually harm the "adverse event observations" of these suicidal cases given by relatives of the victims in the beginning of the hearings. And if that is harmed, one cannot speak of apalling physician care and the independence of suicide from the prescribed drug. It does seem like the pilot has washed his hand and sealed our fate.
I am sorry, I am not able to say more right now.
I intend to read it again. My first impression is that the pharmaceutical companies are very smug, as they have a statistical formula to back up any adverse situation with a drug. The FDA seems to be in the middle, doing the hard work, and the consultants, from whom I think the most sympathetic appreciation of individual suffering comes (for example to mention a few -- Dr. Casper, Dr. Hellander, and Dr. Teicher, Dr. Lieberman, Dr. Zifry), and the necessity for individual care, come last in how effective their objections are and what practical, real impact they have on public health care.Later
Squiggles
Posted by Squiggles on May 14, 2006, at 15:49:16
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Squiggles on May 14, 2006, at 15:06:42
Text correction:
"It does seem like the pilot has washed his hand and sealed our fate."
should read:
"It does seem as if Pilate has washed his hands
and sealed their fate."- sorry;
> Later
>
> Squiggles
Posted by Larry Hoover on May 15, 2006, at 9:54:44
In reply to Re: Statistical question on SSRIs - ADDENDUM, posted by linkadge on May 14, 2006, at 1:26:14
> Is it the drug that caused the suicides? Absolutely, in my opinion. In some of these cases, had the drug not been introduced, lives may not have been lost. But, I do think that there may be genetic predispositions to SSRI induced akathesia and suicidal behavior that do not fall under the category of "latent bipolar".
Link, I feel your pain so bad that I almost fear trying again. I don't mean to question your personal experience and wisdom. I don't question you when I question the issues themselves.
I nearly lost my life to antidepressants. But I can't help other people if I let my bias stand in the way of my science.
If antidepressant drugs caused a suicide, how would you demonstrate that to another person? How could you show that it was this one lone variable that made the difference?
This article that Squiggles dug up explores all of the possible interpretations of the collected data. It's an excellent summary of the process that human beings use to try and clear the scientific arena of bias and logical fallacies. I am not inferring which belief is biased and which is pure. I just want to look at the arguments themselves.
Anecdote. What is anecdote? It is an uncontrolled experiment with one subject. What have you got when you collect one thousand anecdotes? One thousand different uncontrolled experiments with one thousand different subject populations. Anecdote is a point in space. How do you extrapolate from one point?
Anecdote spurs people to create hypotheses, and to consider experiments not yet done. How could you design an experiment which would demonstrate this suicidality, this inductive effect? The fact is that you can't. Any experiment that could do so is absolutely unethical to perform.
Blame helps no one. Except the lawyers.
All we can really do, IMHO, is to manage the drugs better than we did before. Serious drugs for a serious disease require serious management. I cannot fathom how the latter was allowed to detach itself from the former, but we let that happen. Thalidomide taught us a lot. It turns out that thalidomide is a miracle drug, when used in other contexts than for morning sickness.
It's the human component that we can influence. No amount of posturing will affect the drugs themselves. They are what they are. We have a people problem, not a drug problem, IMHO.
Lar
Posted by Squiggles on May 15, 2006, at 11:58:43
In reply to Re: Statistical question on SSRIs - ADDENDUM » linkadge, posted by Larry Hoover on May 15, 2006, at 9:54:44
Try again:
My message disappeared just after writing it
and posting. It was lengthy and took me some
time to compose. A registration request came
right after and it disappeared.OK - let me just say this briefly; perhaps there
is a limit to how much babbling is permitted here;Statistical significance is an advantageous and
unbeatable weapon for the pharmaceutical companies. You cannot argue with statistical significance regarding the efficacy of drugs, or for that matter any other consumer product. Causality seems obsolete, but I am not going to question which scientific method is better or worse.What I would like to suggest, is that statistics give corporations an unfair legal power, which individual citizens and small groups of citizens may not have. Corporations have obligations and are considered as bodies just like people, but they do not have rights. They are infact immune to statistically non-significant harm caused by their product because statistical evidence is on their side. If they hire a lawyer or an army of lawyers to defend the corporation, it will not be against harm done to their sales on account of criticism of a product but only to protect themselves from a statistically significant proof that their product has caused harm.
So, an anecdotal case or group of cases which does not meet this scientific criterion of a large class being harmed, has little recourse but to go to hire a lawyer, no matter how great and undeniable the evidence of the harm done is. Even if the evidence they have as a small group, is statistically significant. They have to pass the test.
If I am right in this, the government has actually fallen in its obligation to protect the rights of the minority against the majority. And it has done so in a manner which it is very difficult to extricate itself from, because proof in our legal system requires evidence and what is evidence according to science today? In these matters,
it is statistical significance.Squiggles
Posted by SLS on May 15, 2006, at 12:54:42
In reply to Re: Statistical question on SSRIs - ADDENDUM » linkadge, posted by Larry Hoover on May 15, 2006, at 9:54:44
It must be difficult to tease out from existing data the statistical rate at which an antidepressant drug induces a suicidal state that is not an artefact of an improvement in the depressive state produced by that drug. Some percentage of suicides are the result of a drug performing the task we ask it to.
- Scott
Posted by Larry Hoover on May 15, 2006, at 14:53:05
In reply to Re: Statistical question on SSRIs - ADDENDUM, posted by SLS on May 15, 2006, at 12:54:42
> It must be difficult to tease out from existing data the statistical rate at which an antidepressant drug induces a suicidal state that is not an artefact of an improvement in the depressive state produced by that drug. Some percentage of suicides are the result of a drug performing the task we ask it to.
>
>
> - ScottPrecisely.
Yet, the sum of the (hypothetically) induced, and the natural incidence, is what we now observe. The upper bound of the induced, must be, perforce, the total observed incidence of all suicides. But, that limiting case would itself require that the natural incidence has gone to zero. So, the worst case scenario for induction would also be the best case scenario for overall efficacy.
Lar
Posted by Larry Hoover on May 15, 2006, at 14:57:10
In reply to Re: Statistical question on SSRIs - ADDENDUM » Larry Hoover, posted by Squiggles on May 15, 2006, at 11:58:43
> Statistical significance is an advantageous and
> unbeatable weapon for the pharmaceutical companies. You cannot argue with statistical significance regarding the efficacy of drugs, or for that matter any other consumer product.Statistical significance is not proof of anything at all. One underlying assumption that never goes to zero is that the results are purely and entirely due to chance.
If you sample a population enough times, you can always find a significant result, no matter how absurd the hypothesis being tested.
Much of the research that has been published is not proof of anything at all.
Lar
Posted by Squiggles on May 15, 2006, at 16:57:28
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Larry Hoover on May 15, 2006, at 14:57:10
...........
> Statistical significance is not proof of anything at all. One underlying assumption that never goes to zero is that the results are purely and entirely due to chance.
>
> If you sample a population enough times, you can always find a significant result, no matter how absurd the hypothesis being tested.
>
> Much of the research that has been published is not proof of anything at all.
>
> LarIs this an opinion that you hold Larry or
is it one that the medical community and
especially the psychopharmacology community
goes by? Because Dr. Nemeroff (and the others,
e.g. Kessler) in this early 1991 FDA hearing on suicidality and antidepressants, states the following:"The real issue is how can we, scientifically, as a profession, come to grips with this difficult issue? Clearly, what we need are double-blind placebo-controlled trials. I would like to read a quote from David Kessler, Commissioner Od
the FDA. In his recent article in the New England Journal of Medicine, he said, "scientific rigor requires that data presented during an activity be reliable, that is, capable of
forming an appropriate basis for medical decision making."Scientifically rigorous data are developed through study designs that minimize bias. Anecdotal evidence and unsupported opinion should play no part in a scientifically rigorous program."
So the issue, then, is what, on the one hand, can we learn from case reports and anecdotal data, and I think it car give us a signal for prospective studies. I remind all of you that the history of medicine is replete with examples of
medical decision making based on anecdotal case reports, to wit, the use of widespread tonsillectomies in all of our
children -- at least not our children, but there are very few people in this room who have tonsils. We have now discovered that that was unnecessary surgery, and how did we discover it? By prospective controlled trials.".....
pp. 201-202I don't mean to say that I know what scientific
proof is, but it certainly seems that statistical significance is the lingua franca of what is acceptable as scientifically valid today. Even if this method proved nothing, it certainly has a great impact on public health care if it is universally accepted by clinicians and doctors.Squiggles
Posted by Larry Hoover on May 15, 2006, at 22:37:15
In reply to Re: Statistical question on SSRIs - ADDENDUM » Larry Hoover, posted by Squiggles on May 15, 2006, at 16:57:28
> ...........
>
>
> > Statistical significance is not proof of anything at all. One underlying assumption that never goes to zero is that the results are purely and entirely due to chance.
> >
> > If you sample a population enough times, you can always find a significant result, no matter how absurd the hypothesis being tested.
> >
> > Much of the research that has been published is not proof of anything at all.
> >
> > Lar
>
>
>
> Is this an opinion that you hold Larry or
> is it one that the medical community and
> especially the psychopharmacology community
> goes by?I was speaking my opinion, of course. How could I speak for these other people I've never met? I'm talking about critical thinking. About the limits of scientific "proof". People like the idea that there might be proof, but science doesn't very often prove anything at all. When we say something is statistically significant, the very statement itself includes an assumption that the difference found between groups could be chance. That's what p < .05 indicates. Or, p < .01, or whatever. p is (virtually) never zero.
> Because Dr. Nemeroff (and the others,
> e.g. Kessler) in this early 1991 FDA hearing on suicidality and antidepressants, states the following:
>
> "The real issue is how can we, scientifically, as a profession, come to grips with this difficult issue? Clearly, what we need are double-blind placebo-controlled trials. I would like to read a quote from David Kessler, Commissioner Od
> the FDA. In his recent article in the New England Journal of Medicine, he said, "scientific rigor requires that data presented during an activity be reliable, that is, capable of
> forming an appropriate basis for medical decision making."You can still make a scientific decision, absent proof. Scientists know that they aren't basing decisions on proof, the way lay people know proof. This isn't fingerprint analysis, or DNA analysis we're discussing. (And even those have error estimates attached.)
> Scientifically rigorous data are developed through study designs that minimize bias. Anecdotal evidence and unsupported opinion should play no part in a scientifically rigorous program."
"Anecdote.....should play no part..."
Precisely.
> So the issue, then, is what, on the one hand, can we learn from case reports and anecdotal data, and I think it car give us a signal for prospective studies. I remind all of you that the history of medicine is replete with examples of
> medical decision making based on anecdotal case reports, to wit, the use of widespread tonsillectomies in all of our
> children -- at least not our children, but there are very few people in this room who have tonsils. We have now discovered that that was unnecessary surgery, and how did we discover it? By prospective controlled trials.".....
>
> pp. 201-202For years, tonsils were routinely removed because a child had a sore throat. Why? Because that's what doctors thought they ought to do. Finally, some courageous souls stood up for scientific rigour, and it was shown that tonsillectomy did not improve a child's health. I.e. p *greater than* 0.05. Some children do benefit from the surgery, and it is still performed. It is no longer routine, however.
> I don't mean to say that I know what scientific
> proof is, but it certainly seems that statistical significance is the lingua franca of what is acceptable as scientifically valid today.You have to consider what is being shown to be significant, also. Far too often, unproven conclusions are published, as if they had been proven. A significant outcome was demonstrated, but it didn't support that which was concluded.
> Even if this method proved nothing, it certainly has a great impact on public health care if it is universally accepted by clinicians and doctors.
>
> SquigglesI have been struggling, as I read your post, to find your argument. I didn't find one. Could you please try again?
Lar
Posted by Squiggles on May 16, 2006, at 7:02:11
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Larry Hoover on May 15, 2006, at 22:37:15
> > ...........
>
> I have been struggling, as I read your post, to find your argument. I didn't find one. Could you please try again?
>
> Lar
>It's not an argument so much; it's a point to
the emphasis medical "science" is putting on
statistical significance. Anecdotal "evidence" which is really no evidence at all but a number of cases outside the scope of statistical explanation, are not examined. They may be statistically insignificant but still merit causal or some kind of explanation, just like every event in the universe.Squiggles
Posted by Larry Hoover on May 16, 2006, at 10:04:04
In reply to Re: Statistical question on SSRIs - ADDENDUM » Larry Hoover, posted by Squiggles on May 16, 2006, at 7:02:11
> > > ...........
> >
> > I have been struggling, as I read your post, to find your argument. I didn't find one. Could you please try again?
> >
> > Lar
> >
>
> It's not an argument so much; it's a point to
> the emphasis medical "science" is putting on
> statistical significance. Anecdotal "evidence" which is really no evidence at all but a number of cases outside the scope of statistical explanation, are not examined. They may be statistically insignificant but still merit causal or some kind of explanation, just like every event in the universe.
>
> SquigglesThank you. That's much clearer for me.
I would never say that anecdote is not examined. It just cannot be the basis for concluding anything. If statistical significance falls short of concluding causation (correlation is not causation), then anecdote is absolutely excluded from that consideration.
What we need to do is to conduct the proper study. I have some experience with determining what parameters would be necessary to obtain a meaningful result. I have consulted on the methodology of a number of studies. I think I have a fair comprehension of the necessary characteristics for determining just what we're looking at. Such a study would probably require hundreds of thousands of subjects. That's my best estimate.
But it is not relevant, IMHO, to even do such a study. What would it tell us? We already know what's missing from the care received by depressed people. It is management of the treatment. That's where we fall short. You can't just hand a depressed person powerful drugs, and leave him on his own.
IMHO, the problem has never been the drugs. It has always been the people who were let down by other people. We haven't taken the illness seriously enough. Don't forget, fifty years ago, nobody talked about mental illness at all. We built great buildings, and populated them with people who otherwise virtually ceased to exist. We haven't come too far from that period of great stigma. Don't kid yourself.
If there was a failing, it was that we believed the marketing agents. The salesmen. Scientists knew all along that there was nothing so special about SSRIs. But once Prozac got onto the cover of Time magazine, this false image of Happy Pills was embedded in the culture. Accountants for the drug companies thought that was a good idea, too. Money poured in. The guys on Wall St. weren't about to kill the golden goose.
We end up facing the fact that we got suckered into buying a lemon of a used car, when we thought we were getting a Mercedes at a really great price. Ya know?
I don't think blame is a good idea. If a deal looks too good to be true........
Lar
Posted by Squiggles on May 16, 2006, at 10:58:16
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Larry Hoover on May 16, 2006, at 10:04:04
..............
> IMHO, the problem has never been the drugs. It has always been the people who were let down by other people. We haven't taken the illness seriously enough. Don't forget, fifty years ago, nobody talked about mental illness at all. We built great buildings, and populated them with people who otherwise virtually ceased to exist. We haven't come too far from that period of great stigma. Don't kid yourself.
>That's an interesting point. It suggests that
there are some causal factors outside the
statistical studies of medication efficacy.
> If there was a failing, it was that we believed the marketing agents. The salesmen. Scientists knew all along that there was nothing so special about SSRIs. But once Prozac got onto the cover of Time magazine, this false image of Happy Pills was embedded in the culture. Accountants for the drug companies thought that was a good idea, too. Money poured in. The guys on Wall St. weren't about to kill the golden goose.It was also the golden drug reviewed as the representative of all SSRIs, and yet had a higher suicidal profile than the others; correct me if i am wrong on this.
>
> We end up facing the fact that we got suckered into buying a lemon of a used car, when we thought we were getting a Mercedes at a really great price. Ya know?I hear ya.
>
> I don't think blame is a good idea. If a deal looks too good to be true........Fair enough.
Squiggles
Posted by Larry Hoover on May 16, 2006, at 11:44:42
In reply to Re: Statistical question on SSRIs - ADDENDUM » Larry Hoover, posted by Squiggles on May 16, 2006, at 10:58:16
> ..............
>
>
> > IMHO, the problem has never been the drugs. It has always been the people who were let down by other people. We haven't taken the illness seriously enough. Don't forget, fifty years ago, nobody talked about mental illness at all. We built great buildings, and populated them with people who otherwise virtually ceased to exist. We haven't come too far from that period of great stigma. Don't kid yourself.
> >
>
> That's an interesting point. It suggests that
> there are some causal factors outside the
> statistical studies of medication efficacy.Suggests? It is most certainly the case. The act of creating a clinical study creates an illusion. No real life person is treated as they treat people in study populations. Efficacy itself is a construct.
> > If there was a failing, it was that we believed the marketing agents. The salesmen. Scientists knew all along that there was nothing so special about SSRIs. But once Prozac got onto the cover of Time magazine, this false image of Happy Pills was embedded in the culture. Accountants for the drug companies thought that was a good idea, too. Money poured in. The guys on Wall St. weren't about to kill the golden goose.
>
> It was also the golden drug reviewed as the representative of all SSRIs, and yet had a higher suicidal profile than the others; correct me if i am wrong on this.I don't think it does. It was simply the most examined. Suicidality of the tricyclics is higher. It doesn't matter, though. It is a class effect of pharmacological treatment of mood disorders. If you're going to treat depression with drugs, you get this effect. You manage that effect effectively, or you don't.
We got rid of asylums. They used to be state of the art. Icepick lobotomies. Insulin shock. What people need is care.
Lar
Posted by Squiggles on May 16, 2006, at 16:08:37
In reply to Re: Statistical question on SSRIs - ADDENDUM » Squiggles, posted by Larry Hoover on May 16, 2006, at 11:44:42
...........
> We got rid of asylums. They used to be state of the art. Icepick lobotomies. Insulin shock. What people need is care.
>
> Lar-----------------
-----------------
It looks like we're going around and around and around.
Look what i found from two years ago: From LAXAT.com http://www.laxat.com/Effexor-can-enlarged-lymph-nodes-be-side-effect-1502549.html
You can follow the thread here at the above url.[Example of discussion:]
Larry Hoover Apr 14, 2004 07:29I'll answer the other question, too. Genotoxic means that a substance
affects either the "data" stored in DNA, or interferes with the DNA's
ability to be "translated" into RNA. It's a functional interference with DNA
(usually caused by chemical or conformational changes in the DNA structure).
It's conceivable that germ cells (those specialized cells that become sperm
or egg) may also be affected, but interference with that DNA would almost
exclusively lead to failed reproduction, not survivable mutation.
The C-6 glioma concept refers to a commercial laboratory cell line, a
so-called "immortal" cell culture that you can buy from suppliers. It's one
of the "stardard" cell cultures. Gliomas are cancer cells, arising from
aberrant glial cells (support cells for neurons, such as astrocytes). The
C-6 refers to a specific culture, and the origin is rat brains. This
particular cell culture, although it arises from a cancer, is stable. It is
a curiousity of science that we can say that a certain drug will induce
cancerous changes in cells that are already cancerous, non?
It takes an extraordinary leap of inference, IMPNSHO, to extrapolate from in
vitro studies of (cancerous) rat brain cells, most often employing
concentrations of a potential toxicant (e.g. a tricyclic antidepressant)
never found in human brains at normal therapeutic dosage, and conclude that
the toxicant is a threat to human health.
I'm going to climb on to a soapbox now.
Major depression is associated with a direct mortality of about 15%
(lifetime morbid risk), via suicide. Indirectly, it is also associated with
substantially increased risk for heart disease, stroke, cancer, endocrine
disturbances, immune dysfunction, and a variety of comorbid psychiatric
disturbances with their own health risks. The social and familial financial
burdens associated with major depression are difficult to assess accurately,
but must be quite large. Serious dysfunction requires serious medicine, and
serious medicine often entails serious risk. But, a percentage of a
percentage is always smaller than the original number.
Much of the negative propaganda being circulated today arises from a
mistaken assessment of the actual risk and benefit of medical intervention.
A classic example is the "popularity" today of foregoing vaccination. There
may conceivably be an increased risk of some rare disorders arising directly
from vaccination (the evidence is absent in studies in Denmark, where the
medical histories of every citizen are known to the government), but people
rejecting that form of protection against disease are overlooking the
effects of the disease itself. Measles can be fatal, or confer lifelong
disability. Mumps, whooping cough, polio......these are not trivial
common-cold-like disorders. The vaccines were developed to protect people
from debilitating illness. Governments and scientists didn't invest so much
effort and expense into protecting the population for no good reason. Where
is the true risk here?
I'm happy to discuss the evidence, but conspiracy theories, and lawyers
chasing lawsuits, really piss me off. Drug companies haven't been totally
ethical, but we can deal with that. Ford wasn't totally ethical with the
Pinto, either. We got over it.
We cannot gain knowledge without taking risks. Let's not let the risk keep
us from gaining knowledge.
Lar"
> > ..............
You say that what mentally ill people really
need is *care*. What do you mean by care? Certainly we cannot get rid of drugs. You state above that:"Much of the negative propaganda being circulated today arises from a
mistaken assessment of the actual risk and benefit of medical intervention."What kind of medical intervention are you
referring to? What would we have left if
we got the risk/benefit assessment right?Squiggles
Posted by Larry Hoover on May 16, 2006, at 16:26:30
In reply to Re: Statistical question on SSRIs - ADDENDUM » Larry Hoover, posted by Squiggles on May 16, 2006, at 16:08:37
>
>
> ...........
> > We got rid of asylums. They used to be state of the art. Icepick lobotomies. Insulin shock. What people need is care.
> >
> > Lar
>
> -----------------
> -----------------
>
>
> It looks like we're going around and around and around.
>
>
> Look what i found from two years ago: From LAXAT.com http://www.laxat.com/Effexor-can-enlarged-lymph-nodes-be-side-effect-1502549.html
> You can follow the thread here at the above url.
>
> [Example of discussion:]At least I am consistent. I could have written that today.
(snip)
>
> You say that what mentally ill people really
> need is *care*. What do you mean by care?What if we were so wealthy, as a culture, that each person had a physician whose sole purpose was to restore one single person to health? That is an enhancement in care.
Care is contextual. Care is more easily defined by its absence, as by giving a depressed person a powerful drug, giving them no instructions vis a vis suicidal concerns, and telling them to return for another 10 minute session in 3 months time, during which 8 minutes is wasted in trying to remind the doctor who the hell you are.
> Certainly we cannot get rid of drugs. You state above that:
I have never suggested that we should.
> "Much of the negative propaganda being circulated today arises from a
> mistaken assessment of the actual risk and benefit of medical intervention."
>
> What kind of medical intervention are you
> referring to?Any medical intervention. Any one.
> What would we have left if
> we got the risk/benefit assessment right?
>
> SquigglesOptimal care.
Lar
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