![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 92 to 116 of 116. Go back in thread:
Posted by JLM on August 14, 2004, at 8:45:13
In reply to Re: So, marilyn, please don't drop dead, posted by SLS on August 14, 2004, at 8:27:00
> > That doesn't wash. Lilly could have went ahead and
> > carried out the Beasly Protocol, as they had promised the FDA, and chose not to. Is that perhaps because they feared what the result would be?
>
>
> I am not at all familiar with this. Were they asked to do this in the early 1990s in association with the law suits? I'm sure they did fear what the result would be. Someone must have had some suspicians. What is the Beasly Protocol?
>
> Thanks.
>
> You might want to take a look at the Cymbalta labelling. It does cite treatment-emergent suicides as an infrequent occurrence.
>
>
> - ScottScott:
"The short attachments to this paper contain deposition transcript excerpts and a couple of exhibits from a public domain deposition of Eli Lilly's Dr. Charles Beasley. Dr. Beasley was, for several years, Lilly's "point man" on the issue of SSRI induced suicidality. It was he who flew immediately from Indianapolis to Boston, in January of 1990, to meet with Dr. Martin Teicher in an attempt to neutralize the now famous Teicher & Cole articleii. It was he who authored the "meta-analysis" of Lilly's studies, an analysis which, among other serious flaws, excluded 76 out of 97 actual suicides! And it was this same Dr. Beasley who was the principal author of a study protocol, written with the input of "somewhere between 10 and 100" in-house and outside scientists. But more of that below.
On one particular day in late 1990 or early 1991, Dr. Beasley was a scrivener. His attached handwritten notes chronicle the concerns and recommendations of several very prominent outside consultants. These private concerns, voiced only in the veiled secrecy of the hallowed halls of Lilly corporate headquarters. Dr. Gary Tollefson, who would later come in-house and rise to a high executive level position at Lilly, said that it is "possible [that a] small # get paradox." (See my Puzzling Paradox of Prozac Induced Suicidality graphic at www.JusticeSeekers.com.) When he was still on the outside looking in, Dr. Tollefson suggested that the "risk" was related to "akathisia" and he recommended prospective studies of "agitated dp [depression], using sophisticated suicide scales." He even intimated that the study results should be "published."
Dr. Jan Fawcett realized that the company had "group data," but told Lilly that it "should look at cases." This Committee will hear many compelling cases. Big Pharma will urge you to brand them as mere "anecdotes" and relegate them to the field of "hypothesis generators." But, as Dr. Fawcett obviously realized, considerable scientific truth inheres in each of these cases. Each merits careful, individual evaluation.
But it was Dr. Jerold Rosenbaum, one of the chief public apologists for Lilly in 1991iii , that put it most bluntly:
data problems . . . if exist won't find " don't look " means find then rechallenge
Why was it that Dr. Rosenbaum was so concerned about finding the phenomenon by reviewing the existing data? He doesn't say. But there are many reasons why he should have been. One was that nobody was looking for the phenomenon when the data was gathered. The investigators were not sensitive to it and the rating scales were inadequate to detect it. Another was that seriously suicidal people were excluded from most of the clinical trials. Another was the drop outs or "lost to follow up." Yet another was the assumed rarity of the phenomenon. If it was as rare as Teicher and Cole themselves postulated, then it would take a very large study indeed to have adequate statistical "power" to detect and measure it. These and other reasons militated against finding the "needle in the haystack."
But another reason, one about which I queried Dr. Beasley in the deposition, was what I shall call the "robbing Peter to pay Paul" phenomenon. It was expressed to Lilly by Dr. Gordon Parker of New South Wales in a letter dated August 24, 1990. If, as everyone was willing to assume, Prozac was an effective antidepressant, then it would certainly reduce suicidality for some patients. Dr. Parker assumed a 15% reduction of suicidality in the fluoxetine (FT) group. ABut what if a small percentage (say 1%) of the FT patients had a paradoxical increase in suicidal ideation. The overall analysis would show FT to be superior to PT as both a general antidepressant and in reducing suicidal ideation " and the paradoxical side-effect phenomenon would be buried." Buried! Like a needle in the haystack!
So, back to Dr. Rosenbaum's recommendation. "Find then rechallenge." What result would that yield? As noted above, somewhere between 10 and 100 Lilly scientists rejected RCT's and rejected large scale epi studies in favor of this prospective study design. Find the group which Dr. J. John Mann had labeled as a "small vulnerable subpopulation" of patients, and rechallenge them, in protected circumstances, with Prozac. In the spring of 1991 Lilly met with officials at the FDA and pledged to conduct the Beasley Rechallenge Protocol. But Lilly reneged on that pledge, and to its shame and discredit, the FDA did not force them to honor it. Consequently, there has been no systematic study via rechallenge.
However, many of the "cases" before this Panel have elements of challenge-dechallenge and rechallenge. So, too, do many of the "case reports" published in peer reviewed journals. The most dramatic example, of course, is the 1991 article by Rothschild & Lockeiv. In 1991, years before he became a paid litigation expert for Eli Lilly, Anthony Rothschild and his colleague wrote that "the Patients need to be reassured that the overwhelming symptoms [of akathisia and its concomitant suicidality] being experienced are the side effects of medication and are treatable."
IF this Committee really wants to get a handle on the issue, then it should couple its laudable comprehensive review of the existing data with an insistence of appropriately designed and conducted, independent, prospective studies, preferably via rechallenge.
This will take time. In the meantime, in view of the paucity of evidence of real antidepressant efficacy in the children/adolescent population, the Committee should recommend that the FDA couple a contraindication of all SSRI's for children/adolescents with a warning about the very real dangers of SSRI induced suicidality and aggression. There are those who will argue that such a "ban" will deprive those patients who benefit from these drugs of their drug of choice. Not true. Informed physicians and informed patients can still choose to encounter the risks. After all, the Supreme Court itself has held that "off label" prescribing is still legal in this country. "
If you want to test whether a side effect is indeed REAL, then a simple way to do it is:
1. give it to a healthy volunteer
2. see if it happens
3. if it does, take them off the drug, and see
if it resolves.
4. give them the drug AGAIN, and see if they become suicidial again.Challenge/Dechallenge/Rechallenge
That is what Dr. Beasely proposed, what Lilly promised the FDA, and what was never carried out.
And obviously you want to give the drug to a healthy volunteer, so you don't have the easy out of 'well of course they killed themselves, they were depressed'
Posted by theo on August 14, 2004, at 9:15:18
In reply to Re: So, marilyn, please don't drop dead » SLS, posted by JLM on August 14, 2004, at 8:45:13
Is there a "healthy" blood test? Do they get hooked up to a lie detector? No! They do just what the word means, volunteer. The woman that committed suicide had tried before and had she disclosed this, there is know way they would have included her in the drug trial.
Yes, I would be upset if she were my daughter, but would also realize she did volunteer and not try to place the blame on someone else.
Posted by alesta on August 14, 2004, at 9:16:28
In reply to Re: So, marilyn, please don't drop dead, posted by SLS on August 13, 2004, at 14:10:33
hi, scott,
i'm not siding with anybody here (i'm staying out of THIS one), but did you say in another post that you have dementia? are you kidding me? you’re brilliant! no worries. :)
-Amy
Posted by JLM on August 14, 2004, at 10:05:11
In reply to How do you know the volunteer is healthy? » JLM, posted by theo on August 14, 2004, at 9:15:18
> Is there a "healthy" blood test? Do they get hooked up to a lie detector? No! They do just what the word means, volunteer. The woman that committed suicide had tried before and had she disclosed this, there is know way they would have included her in the drug trial.
>
> Yes, I would be upset if she were my daughter, but would also realize she did volunteer and not try to place the blame on someone else.Ummm, unbelievable really....
If Lilly's TRAINED psychiatrists can't reliably distinguish between healthy people and sick people, then perhaps they shouldn't have MD licenses. I mean, I call me funny but ;)
Posted by JLM on August 14, 2004, at 10:16:56
In reply to Re: So, marilyn, please don't drop dead--SLS, posted by alesta on August 14, 2004, at 9:16:28
Once again we're back to the standard Corporate line
from Lilly.The argument seems to be that even thou she was in a healthy volunteer study, she had a history of depression, and that being the case, its obvious
that our wonderful pill wasn't the cause of her suicide.Well, in order to believe that, you have to believe that Lilly's clinical investigators are so incompetent as to mislabel a 'sick' person as healthy for the purposes of the trial. Or that they use extreme shoddy screening procedures. Or both for that matter.
I question whether they should even be conducting
clinical trials at all if they are that incompitent.So you have two options:
1. she really was NOT a healthy volunteer, and Eli
Lilly's crack scientists just happened to miss that. Wow, I'm sure impressed with their scientific prowess2. she really WAS a healthy volunteer, and Cymbalta was the cause
and just for fun I'll add option 3.
3. the Easter Bunny made her do it.
Posted by Marilyn on August 14, 2004, at 10:50:00
In reply to Re: If this would be your daughter,how would you feel?, posted by SLS on August 14, 2004, at 8:01:51
> Do you know this person? That's all I really want to know.
Dear Scott,
That is a much better question. Yes, I know this person personally.
> You seem to have told a story that you have no
> personal knowledge of.That is a very cheap pure speculative assumption. And is not true either. I have personal knowledge of the story I told.
> What would you like to see happen with
> duloxetine?Obviously you seem to have problems to answer my question Scott. Instead you ask me this question which is totally unrelevant. It doesn't matter. I think I have made my point clearly enough to you.
Marilyn
Posted by theo on August 14, 2004, at 10:56:17
In reply to Re: How do you know the volunteer is healthy? » theo, posted by JLM on August 14, 2004, at 10:05:11
A psychiatrist can only help someone that's honest. If you're running down the street naked, that's one thing. If a person who is depressed walks in and says they are fine and never attempted suicide, are you telling me a psychiatrist can see inside their mind and go nope, I can tell, because I am a doctor, that you have attemted suicide in the past.
I psychiatrist is only helpful when you tell them your condition, they are not mind readers and anyone can act one way when they are feeling completely the opposite when they want something, it's called acting.
Posted by SLS on August 14, 2004, at 11:23:29
In reply to Re: How do you know the volunteer is healthy? » theo, posted by JLM on August 14, 2004, at 10:05:11
> > Is there a "healthy" blood test? Do they get hooked up to a lie detector? No! They do just what the word means, volunteer. The woman that committed suicide had tried before and had she disclosed this, there is know way they would have included her in the drug trial.
> >
> > Yes, I would be upset if she were my daughter, but would also realize she did volunteer and not try to place the blame on someone else.
>
> Ummm, unbelievable really....
>
> If Lilly's TRAINED psychiatrists can't reliably distinguish between healthy people and sick people, then perhaps they shouldn't have MD licenses. I mean, I call me funny but ;)
>This young woman was in dire need of money to continue her education. I fear that she might have made herself look very acceptable as a healthy volunteer.
- Scott
Posted by JLM on August 14, 2004, at 11:45:38
In reply to Re: How do you know the volunteer is healthy? » JLM, posted by theo on August 14, 2004, at 10:56:17
> A psychiatrist can only help someone that's honest. If you're running down the street naked, that's one thing. If a person who is depressed walks in and says they are fine and never attempted suicide, are you telling me a psychiatrist can see inside their mind and go nope, I can tell, because I am a doctor, that you have attemted suicide in the past.
>
> I psychiatrist is only helpful when you tell them your condition, they are not mind readers and anyone can act one way when they are feeling completely the opposite when they want something, it's called acting.So, the MADRS and HAM-D are invalid measuring insruments? After all these are the instruments
that are used in clinical trials to establish the
benefit of the drug. Should we not trust these either since the patietnt migth be 'acting'? If you assume that, then you should also assume that
the results of any clinical trial for AD are probably not valid. You can't have valid results
without a valid way to measure them.See, I thought depression was like diabetes. At least I have/had read that on some promo material from Lilly/GSK/Forrest. Hrm......
Posted by theo on August 14, 2004, at 11:57:28
In reply to Re: How do you know the volunteer is healthy?, posted by JLM on August 14, 2004, at 11:45:38
You just don't get it, the girl went in for a drug trial, not a psychiatric evalution with the interest of getting better and totally admitting what she had been through in the past.
All of the instruments you mentioned are good when you are seeking help and laying all the cards on the table, not lying on an application for financial purposes.
Posted by SLS on August 14, 2004, at 12:05:43
In reply to Re: If this would be your daughter,how would you feel?, posted by Marilyn on August 14, 2004, at 10:50:00
> > Do you know this person? That's all I really want to know.
> Dear Scott,
> That is a much better question. Yes, I know this person personally.
I could not have guessed otherwise, and you did defer confirming this for quite some time. I thought it was just another one of your "antidepressants.com" stories that you saw fit to list in your prior posts. Your personal knowledge of an event contrasts greatly with the many third person accounts of unsubstantiated and unstudied drug-related horror stories that litter the Internet. It wasn't a cheap shot. It was a legitimate attempt to assess the credibility of your story.Yours is a horror story. Maybe there is someone on this forum whom could help you. Like I said, I have no reason to exclude the possibility that many of the neurological phenemonena you describe are related to the eposure of this person to citalopram. Do you know which drugs have been tried to treat the neuralgia?
> > What would you like to see happen with
> > duloxetine?
> Obviously you seem to have problems to answer my question Scott.Yes I do. It was rhetorical. Would you expect me to say that I would be in a state of bliss to know that my daughter was disabled by a poison?
Please.
It is obvious that we both have an emotional stake in this issue. You have not answered any of the questions I have asked you. I declined to answer but one of yours.
- Scott
Posted by SLS on August 14, 2004, at 12:19:33
In reply to Re: So, marilyn, please don't drop dead » SLS, posted by JLM on August 14, 2004, at 8:45:13
> Scott:
"The short attachments to this paper contain deposition transcript excerpts and a couple of exhibits from a public domain deposition of Eli Lilly's Dr. Charles Beasley. Dr. Beasley was, for several years, Lilly's "point man" on the issue of SSRI induced suicidality. It was he who flew immediately from Indianapolis to Boston, in January of 1990, to meet with Dr. Martin Teicher in an attempt to neutralize the now famous Teicher & Cole articleii. It was he who authored the "meta-analysis" of Lilly's studies, an analysis which, among other serious flaws, excluded 76 out of 97 actual suicides! And it was this same Dr. Beasley who was the principal author of a study protocol, written with the input of "somewhere between 10 and 100" in-house and outside scientists. But more of that below
<the rest of this post was excised by me>
*****************************************
Please forgive me if I'm wrong, but it looks like you copy-and-pasted this from somewhere. What's with the quotation marks? Where did you find this? This seems pretty disingenuous to be made by you as an argument.Anyway, I just asked what the Beasley protocol was.
Is this it?:> If you want to test whether a side effect is indeed REAL, then a simple way to do it is:
>
> 1. give it to a healthy volunteer
> 2. see if it happens
> 3. if it does, take them off the drug, and see
> if it resolves.
> 4. give them the drug AGAIN, and see if they become suicidial again.
Thanks.
- Scott
Posted by Dr. Bob on August 15, 2004, at 17:23:49
In reply to Re: So, marilyn, please don't drop dead » JLM, posted by SLS on August 14, 2004, at 12:19:33
> This seems pretty disingenuous to be made by you as an argument.
Please don't post anything that could lead others to feel accused or put down.
Anyone who has questions about this or about posting policies in general, or who is interested in alternative ways of expressing themselves, should see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Also, follow-ups regarding these issues should be redirected to Psycho-Babble Administration.
Thanks,
Bob
Posted by SLS on August 16, 2004, at 7:51:23
In reply to Re: please be civil » SLS, posted by Dr. Bob on August 15, 2004, at 17:23:49
> > This seems pretty disingenuous to be made by you as an argument.
>
> Please don't post anything that could lead others to feel accused or put down.Sorry.
You are extraordinarily thorough.
:-)
Thanks.
- Scott
Posted by JLM on August 16, 2004, at 8:04:02
In reply to Re: please be civil, posted by SLS on August 16, 2004, at 7:51:23
> > > This seems pretty disingenuous to be made by you as an argument.
> >
> > Please don't post anything that could lead others to feel accused or put down.
>
> Sorry.
>
> You are extraordinarily thorough.
>
> :-)
>
> Thanks.
>
>
> - Scott
>
>
>
>
>
>
Scott, its not a big deal really. I didn't take offense at anything you said.The reason I posted that whole quotation was to give the readers some historical context on Dr. Beasley, as well as an explanation of what the protocol actually was/is, allthou I don't think in retrospect it does a very good job.
The idea with a challenge/dechallenge/rechallenge
is fairly simple: if give someone a drug once and you see a particular side effect, you can't really
be sure of causation. But, if you give it to them AGAIN, and you see the same thing happen again, then you can be reasonably certain that it was indeed the drug. Especially if you give it to a healthy volunteer.The problem with using RCT's to look at side effects is somewhat multifaceted. For one thing, since AD's seem on the whole to be PROTECTIVE against suicide, you will have the masking effect
mentioned in the quotation. IE, since the drug (potentially) prevents more suicides than it causes then its negative effects will be masked.The other thing is that most reports of side effects are patient reported, and not elicted by the clinical examiner. In other words, the doctors rely upon the patients to tell THEM what if any side effects they are experiencing, exclusive of course of things that would show up on lab tests. And patients have a tendency to underreport when they aren't SURE its a SE.
And yes, you DO see warnings about suicides in the
latest PDA entries but to me they are still somewhat misleading:Fluoxetine:
Suicide
The possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high risk patients should accompany initial drug therapy. Prescriptions for fluoxetine HCl should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.
Because of well-established comorbidity between both OCD and depression and bulimia and depression, the same precautions observed when treating patients with depression should be observed when treating patients with OCD or bulimia.
Okay, you notice its the standard line about how its the ILLNESS ILLNESS ILLNESS. They don't mention that it can be the drug itself.
Posted by JLM on August 16, 2004, at 8:07:05
In reply to Re: How do you know the volunteer is healthy? » JLM, posted by theo on August 14, 2004, at 11:57:28
> You just don't get it, the girl went in for a drug trial, not a psychiatric evalution with the interest of getting better and totally admitting what she had been through in the past.
>
> All of the instruments you mentioned are good when you are seeking help and laying all the cards on the table, not lying on an application for financial purposes.
I'm a bit confused. How do the Lilly investigators know that they have a 'healhy volunteer' WITHOUT doing a psychiatric evaluation? I'm willing to accept the possibility that they didn't do one, but if that's the case, that's rather disturbing IMO.If they don't do one as a matter of course, perhaps they should when testing psych meds? That would seem to be a wise course.
Posted by Larry Hoover on August 16, 2004, at 9:22:20
In reply to Re: please be civil, posted by JLM on August 16, 2004, at 8:04:02
> The idea with a challenge/dechallenge/rechallenge
> is fairly simple: if give someone a drug once and you see a particular side effect, you can't really
> be sure of causation. But, if you give it to them AGAIN, and you see the same thing happen again, then you can be reasonably certain that it was indeed the drug. Especially if you give it to a healthy volunteer.True enough, but you cannot exclude alternate explanations for adverse effects in "healthy people" by just defining things a certain way.
If you gave digoxin to "healthy people" it would adversely affect heart function. You can't extrapolate from that to people with low cardiac output. They are distinct populations.
If ADs are associated with increased risk of suicide in non-depressed people, you cannot infer that there is a hidden effect in the depressed population. It's a reasonable thing to consider, but it cannot (yet) be demonstrated.
That said, there is a critical window early on in pharmaceutical treatment of depression (and this is true for virtually all ADs, not just SSRIs), where suicidality is enhanced. It's tempting to blame the drugs for that, but the very reason many people are being treated with ADs is because of the morbid risk of suicidality in depressive disorders. There are many theories about why this increase in suicidal behaviour may occur, but once again, blaming the drugs alone is short-sighted.
Lar
Posted by JLM on August 16, 2004, at 11:35:17
In reply to Re: drug effect on healthy people » JLM, posted by Larry Hoover on August 16, 2004, at 9:22:20
> > The idea with a challenge/dechallenge/rechallenge
> > is fairly simple: if give someone a drug once and you see a particular side effect, you can't really
> > be sure of causation. But, if you give it to them AGAIN, and you see the same thing happen again, then you can be reasonably certain that it was indeed the drug. Especially if you give it to a healthy volunteer.
>
> True enough, but you cannot exclude alternate explanations for adverse effects in "healthy people" by just defining things a certain way.
>
> If you gave digoxin to "healthy people" it would adversely affect heart function. You can't extrapolate from that to people with low cardiac output. They are distinct populations.
>
> If ADs are associated with increased risk of suicide in non-depressed people, you cannot infer that there is a hidden effect in the depressed population. It's a reasonable thing to consider, but it cannot (yet) be demonstrated.
>
> That said, there is a critical window early on in pharmaceutical treatment of depression (and this is true for virtually all ADs, not just SSRIs), where suicidality is enhanced. It's tempting to blame the drugs for that, but the very reason many people are being treated with ADs is because of the morbid risk of suicidality in depressive disorders. There are many theories about why this increase in suicidal behaviour may occur, but once again, blaming the drugs alone is short-sighted.
>
> LarTrue, a healthy population is a healthy population.
But, that's exactly the problem. These drugs are vastly overprescribed, and that being the case, this phenomena is particularly relevent. There are all kinds of people out there, thanks to HMO's/Managed Care, that are walking around on SSRI's that aren't truly depressed. So, this potential phenomena is PARTICULARLY relevent to them.
And, since the proposed mechanism is akathisia, it
would/could be relevent to 'sick' people as well. Look at all the people who got akathisia from antipsychotics. They didn't get akathisia because the drug behaved a certain way in THEIR bodies, they got akathisia because the drugs can cause akathisia in ANYONE, even a healthy person.In the Teicher and Cole articles, the patients they were dealing with were obviously depressed (you wouldn't be seeing someone of the stature of Dr. Cole if you were not sick), and when put thru a challenge/dechallenge/rechallenge, they became suicidial BOTH times they drug was reinstituted. Coincidence? Johnathan O. Cole is one of the most prominent psychopharmacologists in the world. He was a founding member of the ACNP and on their editorial board.
Posted by SLS on August 16, 2004, at 15:17:03
In reply to Re: please be civil, posted by JLM on August 16, 2004, at 8:04:02
> The idea with a challenge/dechallenge/rechallenge
> is fairly simple: if give someone a drug once and you see a particular side effect, you can't really
> be sure of causation. But, if you give it to them AGAIN, and you see the same thing happen again, then you can be reasonably certain that it was indeed the drug. Especially if you give it to a healthy volunteer.
I don't think it is necessarily the point to prove that these drugs precipitate a suicidal state in an otherwise healthy individual. They might never do that. It might be that this happens only in those people who have a biological vulnerability for depression or perhaps only in those people whom express the depressive phenotype. In other words, the inability to get this thing to happen in a healthy volunteer doesn't preclude its happening in unhealthy individuals. Personally, I have been quite vocal in my belief that Prozac and other antidepressants produce suicidal states independent of any clinical antidepressant effect. I also don't believe that the appearance of akathisia is requisite for this to happen. Reboxetine, a selective NE reuptake inhibitor, made me suicidal in the absence of akathisia, but in the presence of anxiety, which Prozac and other SSRIs are well known to cause.
- Scott
Posted by Iansf on August 16, 2004, at 17:20:31
In reply to Re: How do you know the volunteer is healthy?, posted by JLM on August 16, 2004, at 8:07:05
> I'm a bit confused. How do the Lilly investigators know that they have a 'healhy volunteer' WITHOUT doing a psychiatric evaluation? I'm willing to accept the possibility that they didn't do one, but if that's the case, that's rather disturbing IMO.
>I've suffered from depression since I was a teenager, but I think I would have little problem convincing even a very skilled psychiatrist that I had never been seriously depressed in my life. I know how to answer the questions in ways that point to general contentedness. Perhaps I wouldn't "pass" if the psychiatrist spent hours screening me or subjected me to an immense battery of tests and looked closely for descrepancies, but typically that isn't going to happen. And this holds true not just for psychiatry but for all of medicine. I could have dozens of symptoms pointing to a brain tumor, but if I didn't tell the doctors about them, how would they know? Doctors aren't wizards. They're human beings who depend upon the data given them to make a diagnosis. If the data is withheld or hidden, they can't intuit it.
Posted by Larry Hoover on August 17, 2004, at 10:37:48
In reply to Re: drug effect on healthy people, posted by JLM on August 16, 2004, at 11:35:17
I come late to this debate, and I haven't read all that precedes my joining in.
> True, a healthy population is a healthy population.
It is an absolute necessity to consider population issues. They don't preselect depressed people for antidepressant trials for no reason. It is a critical parameter.
> But, that's exactly the problem. These drugs are vastly overprescribed, and that being the case, this phenomena is particularly relevent.That is a straw man argument, vis a vis antidepressant effects. The mismanagement of a drug is not a drug effect.
> There are all kinds of people out there, thanks to HMO's/Managed Care, that are walking around on SSRI's that aren't truly depressed.
I will not argue, in the slightest, with the (in)appropriateness of such prescriptions. The EU has recently brought down restrictions on the prescription of the SSRIs, and recommendations for better monitoring of patients provided with them. They are serious meds, and they have been managed in a very offhand manner.
> So, this potential phenomena is PARTICULARLY relevent to them.
No doubt.
> And, since the proposed mechanism is akathisia, it
> would/could be relevent to 'sick' people as well.Proposed mechanisms are not proof of anything at all. I suspect they reduce the ability to apply logic, not increase it.
> Look at all the people who got akathisia from antipsychotics.
Were you aware that naturalistic studies of schizophrenics in developing nations have shown identical incidence of tardive dyskinesia and akathisia in drug-naive and treated (age-matched) subjects?
> They didn't get akathisia because the drug behaved a certain way in THEIR bodies, they got akathisia because the drugs can cause akathisia in ANYONE, even a healthy person.
It begs the question if something is getting fixed what ain't broke.
> In the Teicher and Cole articles, the patients they were dealing with were obviously depressed (you wouldn't be seeing someone of the stature of Dr. Cole if you were not sick), and when put thru a challenge/dechallenge/rechallenge, they became suicidial BOTH times they drug was reinstituted. Coincidence?
I do not doubt the empirical evidence. The issue for me becomes, "Is it manageable?".
> Johnathan O. Cole is one of the most prominent psychopharmacologists in the world. He was a founding member of the ACNP and on their editorial board.
That is a logical fallacy, an appeal to authority. Einstein was wrong about his "correction" of the Cosmological Constant.
Posted by Larry Hoover on August 17, 2004, at 13:27:28
In reply to Re: So, marilyn, please don't drop dead » SLS, posted by JLM on August 14, 2004, at 8:45:13
> > > That doesn't wash. Lilly could have went ahead and
> > > carried out the Beasly Protocol, as they had promised the FDA, and chose not to. Is that perhaps because they feared what the result would be?
> >
> >
> > I am not at all familiar with this. Were they asked to do this in the early 1990s in association with the law suits? I'm sure they did fear what the result would be. Someone must have had some suspicians. What is the Beasly Protocol?
> >
> > Thanks.
> >
> > You might want to take a look at the Cymbalta labelling. It does cite treatment-emergent suicides as an infrequent occurrence.
> >
> >
> > - Scott
>
>
>
> Scott:
>
> "The short attachments to this paper contain deposition transcript excerpts and a couple of exhibits from a public domain deposition of Eli Lilly's Dr. Charles Beasley. Dr. Beasley was, for several years, Lilly's "point man" on the issue of SSRI induced suicidality. It was he who flew immediately from Indianapolis to Boston, in January of 1990, to meet with Dr. Martin Teicher in an attempt to neutralize the now famous Teicher & Cole articleii. It was he who authored the "meta-analysis" of Lilly's studies, an analysis which, among other serious flaws, excluded 76 out of 97 actual suicides! And it was this same Dr. Beasley who was the principal author of a study protocol, written with the input of "somewhere between 10 and 100" in-house and outside scientists. But more of that below.It is appropriate to provide a reference to quoted material. Where did you find this?
Lar
Posted by Larry Hoover on August 17, 2004, at 13:31:30
In reply to Re: How do you know the volunteer is healthy?, posted by JLM on August 16, 2004, at 8:07:05
> > You just don't get it, the girl went in for a drug trial, not a psychiatric evalution with the interest of getting better and totally admitting what she had been through in the past.
> >
> > All of the instruments you mentioned are good when you are seeking help and laying all the cards on the table, not lying on an application for financial purposes.
>
>
> I'm a bit confused. How do the Lilly investigators know that they have a 'healhy volunteer' WITHOUT doing a psychiatric evaluation? I'm willing to accept the possibility that they didn't do one, but if that's the case, that's rather disturbing IMO.They advertise for healthy volunteers (frequently in university and college newspapers). Those who show up are asked some very trivial screening questions, but that's about it.
> If they don't do one as a matter of course, perhaps they should when testing psych meds? That would seem to be a wise course.
>In hindsight, but then you increase the cost. Phase 1 trials are supposed to be on "Joe and Jill Blow". It's perhaps absurd to think it, but for the purposes of these sorts of phase 1 studies, most people are presumed to be normal and healthy. But, for the purposes of drug marketing, most of us are pathological.
Lar
Posted by Larry Hoover on August 17, 2004, at 13:33:41
In reply to Re: How do you know if a volunteer is healthy?, posted by SLS on August 16, 2004, at 15:17:03
> I don't think it is necessarily the point to prove that these drugs precipitate a suicidal state in an otherwise healthy individual. They might never do that. It might be that this happens only in those people who have a biological vulnerability for depression or perhaps only in those people whom express the depressive phenotype. In other words, the inability to get this thing to happen in a healthy volunteer doesn't preclude its happening in unhealthy individuals. Personally, I have been quite vocal in my belief that Prozac and other antidepressants produce suicidal states independent of any clinical antidepressant effect. I also don't believe that the appearance of akathisia is requisite for this to happen. Reboxetine, a selective NE reuptake inhibitor, made me suicidal in the absence of akathisia, but in the presence of anxiety, which Prozac and other SSRIs are well known to cause.
>
>
> - ScottYa, it could be entirely about liver enzyme isoforms, induction, and inhibition.
Lar
Posted by Dr. Bob on August 17, 2004, at 19:55:20
In reply to Re: please be civil, posted by SLS on August 16, 2004, at 7:51:23
This is the end of the thread.
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