![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by fuzzymind on February 9, 2003, at 16:35:58
I have read some recent articles suggesting that anti depressants are only marginally more effective than placebos, and the efficacy of the drugs during trials is heavily manipulated. During trials, apparently they give placebos first, then eliminate those test subjects who are affected by the placebos, thus sever3ely skewing the results.ALos, double blind tests are not necessarily used.
I had taken about 7=8 different anti-D's, with no results, except drowsiness. One gave me hives.
Posted by Larry Hoover on February 9, 2003, at 17:13:31
In reply to Anti_depressants little more than placebos?, posted by fuzzymind on February 9, 2003, at 16:35:58
> I have read some recent articles suggesting that anti depressants are only marginally more effective than placebos, and the efficacy of the drugs during trials is heavily manipulated.
The most comprehensive meta-analysis of the FDA database of clinical trials was conducted by Dr. Khan. Unfortunately, he is frequently misquoted and misinterpreted.
With respect to the former assertion, I've presented the data below. The latter assertion is false.
>During trials, apparently they give placebos first, then eliminate those test subjects who are affected by the placebos, thus sever3ely skewing the results.
That's simply not true. That would not be double-blind.
>ALos, double blind tests are not necessarily used.
Open trials cannot be used for the purpose of determining efficacy with respect to FDA approval. However, open trials are often used to obtain preliminary evidence of efficacy.
> I had taken about 7=8 different anti-D's, with no results, except drowsiness. One gave me hives.That sucks. I'm sorry to hear that.
About placebo groups in clinical trials:
Placebo groups in clinical trials are not untreated. This is a common misconception among both medical practitioners and laypeople, alike.
Seattle psychiatrist Arif Khan found that in 52% of the trials, the effect of the drug could not be distinguished from the placebo.
http://education.guardian.co.uk/higher/research/story/0,9865,740721,00.htmlFrom http://www.psychiatrictimes.com/p000429.html, written by Khan himself:
"Altogether, 8,731 depressed patients participated in 45 pivotal clinical trials. Of these, 4,510 were assigned to the investigational antidepressants, 1,416 to established antidepressants (imipramine [Tofranil], amitriptyline [Elavil, Endep] or trazodone [Desyrel]) and 2,805 to placebo. Statistical analysis indicated that all of the antidepressants were significantly superior to placebo in decreasing the HAM-D score total. Of note was the positive relationship between duration of clinical trial and reduction of symptoms: the longer the duration of the clinical trial, the greater the decrease in depressive symptoms, regardless of treatment. Among the placebo-treated patients, the reduction in mean total HAM-D scores was 24.7% in four-week trials, 31.5% in five-week trials, 30.5% in six-week trials and 36.1% in eight-week trials. Correspondingly, the reduction with traditional antidepressants was 28.2% in four-week trials, 44% in six-week trials and 48.1% in eight-week trials. The reduction with investigational antidepressants was 40% in four-week trials, 40.5% in five-week trials, 40.6% in six-week trials and 43.9% in eight-week trials (Khan et al., in press). "
**Note this next paragraph, please. Placebo subjects are not untreated.**
"The less-than-impressive results in these and other studies also calls to mind the fact that patients assigned to placebo treatment in clinical trials are not "getting nothing." The capsule they receive is pharmacologically inert but hardly inert with respect to its symbolic value and its power as a conditioned stimulus. In addition, placebo-treated patients receive all of the commonly employed treatment techniques: a thorough evaluation; an explanation for their distress; an expert healer; a plausible treatment; expectation of improvement; a healer's commitment, enthusiasm and positive regard; and an opportunity to verbalize their distress. "
He goes on to include a very important warning about the interpretation of his findings:"A cautionary note is indicated about the generalization of these data to the clinical management of depressed patients. The less-than-impressive difference between drug and placebo in this and other studies of clinical trials does not speak directly to the effectiveness of antidepressants in clinical practice. Participants in antidepressant clinical trials are a highly select group and are not representative of the general population of depressed patients. They are not actively suicidal, they are almost always outpatients who are moderately rather than severely or mildly depressed, and they are free of comorbid physical or psychiatric illness. They are likely to have a higher placebo response rate than more severely ill depressed patients. "
"Furthermore, the primary aim of these studies is not to assess the optimal effect of antidepressants, but rather to rapidly assess efficacy of new drugs so they can be brought to the market. Therefore, dose, duration and diagnosis in clinical trials are not necessarily ideally suited to identify the optimal effects of antidepressants. Accordingly, clinical trials may identify the lower bound of the effect size compared to placebo. "
Posted by mattdds on February 9, 2003, at 17:15:36
In reply to Anti_depressants little more than placebos?, posted by fuzzymind on February 9, 2003, at 16:35:58
I have had similar experiences with antidepressants. I also am familiar with these recently posed questions regarding their efficacy.
30-50% of people respond to placebos during any given trial. Even the better studies (from big pharmacy's point of view) only do marginally better than this. I imagine there are lots of studies that have been done (but not released), which do not show favorable results at all. Also, there is a flat dose-response curve to antidepressants, which seems fishy.
Personally, I can't imagine any drug which would solve depression. It seems way too complex a phenomenon to respond to a simple shotgun approach like "cranking up" the serotonin, or any other neurotransmitter for that matter.
Parenthetically, I do think that anxiety (and anxiolytics) is a different story. The benzos, for example show a clear superiority over placebo. Furthermore, anyone who has taken a benzo knows they have quite obvious calming effects.
This is kinda scary to me, to think that we (presumably) are still stuck in this effete monoamine hypothesis paradigm. Believe it or not, Pharm companies are still looking for more selective serotonin reuptake drugs, or other quasi-scientific ways of tweaking neurotransmitters. I hope consumers become aware of this problem, because as long as we seem happy with them (taking them without obvious benefit), pharm companies are more than happy to keep making more Lexapro's.
Keep in mind I'm not blaming pharm companies or anyone in particular. Nor am I "anti-med", much to the contrary, I long for a day when we have effective treatments for depression, pharmacological or otherwise. This is also just my opinion, and if people derive obvious benefit from SSRI's, GREAT! I am just not convinced they are very specific or effective treatments for depression, in general.
There's my rant! I don't mean to dash hopes or ruin anyone's placebo response. But I feel the truth is our ally, not avoiding the problem and pretending that SSRI's are miracle cure-alls.
Matt
Posted by mattdds on February 9, 2003, at 17:41:30
In reply to Re: Anti_depressants little more than placebos?, posted by Larry Hoover on February 9, 2003, at 17:13:31
Larry,
"Placebo groups in clinical trials are not untreated"
First, I don't wish to engage in a heated argument about this, and I am aware you are probably the most pharmacologically knowlegdable person who posts here.
Just one thing. I agree with you that placebo treatment is still treatment. The alliance with professionals in hopes of getting an effective treatment can affect one's mood. However, this is also true of people getting antidepressant treatment. So don't all these nonspecific treatment factors (e.g. therapeutic alliance, participating in a study, the simple act of taking a pill to try to help yourself) figure in to the AD group's response as well? How do we know that ALL of the benefit we are seeing is from the pharmacological effect? And if these "other" things figure in, doesn't that make the actual drug effect quite small? If they are somehow exempt from that effect, I'd like to know why.
But antidepressants do somewhat better, so isn't that something? Maybe. But it could also be an "unblinding effect", which I'm sure you've heard of. In other words the side effects are fairly obvious to most people, and it quickly becomes apparent who is taking what. This might very well skew the results. Why not use active placebos, like diphenhydramine or something with obvious anticholinergic effects.
My opinion is not totally formed about this topic, and I try to keep an open mind (really!), despite my bad luck with them. But I am pretty convinced there are some major flaws in AD trials.
Respectfully,
Matt
Posted by viridis on February 9, 2003, at 18:10:39
In reply to Re: Anti_depressants little more than placebos? » Larry Hoover, posted by mattdds on February 9, 2003, at 17:41:30
Part of the problem in interpreting the results, too, is that even if a substantial fraction of the treatment group really do improve, you could have a situation in which some other fraction actually get worse, so the net effect is an average change in depression rating that isn't much better than placebo.
Most of us have first-hand experience with the great variation among individuals in drug response. Especially with psychiatric meds, what helps one person may be negative, not just neutral, in another. For example, most SSRIs don't appear to fare too well in placebo-controlled trials. My experience with those I've tried has been very negative, so if I were in the treatment group I'd probably report a worsening of symptoms. Yet, I can't deny that these are great drugs for some people, based on the sometimes-dramatic improvements I've seen in friends who have taken Prozac, Celexa, Paxil, etc.
I guess the real key will be development of tests that more accurately identify the likely cause of an individual's depression. This would allow design of placebo-controlled trials for specific meds targeted to those with markers for particular subtypes of depression (e.g., those associated with reduced serotonin availability vs. those tied more to norepinephrine, etc.). I suspect that if such an approach were feasible, the results in favor of particular ADs would be more impressive.
We're not there yet, but I expect that in the next 5-10 years it will actually be possible to screen for genetic markers associated with specific types of depression (and other mental illnesses). This will allow a much more targeted approach to treatment, instead of the tedious and painful trial-and-error approach that's often necessary now. I have my fingers crossed...
Posted by fachad on February 9, 2003, at 18:35:23
In reply to Re: Anti_depressants little more than placebos?, posted by Larry Hoover on February 9, 2003, at 17:13:31
> >During trials, apparently they give placebos first, then eliminate those test subjects who are affected by the placebos, thus sever3ely skewing the results.
>
> That's simply not true. That would not be double-blind.I'm sure I've read many studies where early responders, whether responding to the active agent, or the control, or the placebo, are dropped from the study.
This is supposed to make the results more valid, by eliminating placebo responders so that all the results are from actual drug effects, vs. placebo response.
Posted by Larry Hoover on February 9, 2003, at 18:48:49
In reply to Re: Anti_depressants little more than placebos? » Larry Hoover, posted by mattdds on February 9, 2003, at 17:41:30
> Larry,
>
> "Placebo groups in clinical trials are not untreated"
>
> First, I don't wish to engage in a heated argument about this, and I am aware you are probably the most pharmacologically knowlegdable person who posts here.Well, I don't know about that, but thanks for the compliment.
> Just one thing. I agree with you that placebo treatment is still treatment. The alliance with professionals in hopes of getting an effective treatment can affect one's mood. However, this is also true of people getting antidepressant treatment. So don't all these nonspecific treatment factors (e.g. therapeutic alliance, participating in a study, the simple act of taking a pill to try to help yourself) figure in to the AD group's response as well?
Yes, and that's why both groups must be treated identically, in all respects, except for the active treatment.
>How do we know that ALL of the benefit we are seeing is from the pharmacological effect?
We don't try and interpret the results that way. What is important is the difference in response between the groups. It is inferred that the difference is the pharmacological effect.
>And if these "other" things figure in, doesn't that make the actual drug effect quite small?
Yes, in absolute terms, a 15% difference is pretty typical. E.g. 35% placebo response, vs. 50% pharmacological response. But, focussing solely on that one characteristic overlooks the fact that clinical practice offers a good deal of the other aspects of treatment as a matter of course. In other words, one would expect much greater than 15% response to active antidepressant treatment in the general population.
>If they are somehow exempt from that effect, I'd like to know why.
>
> But antidepressants do somewhat better, so isn't that something? Maybe.That's the nature of a clinical trial, though.
>But it could also be an "unblinding effect", which I'm sure you've heard of. In other words the side effects are fairly obvious to most people, and it quickly becomes apparent who is taking what. This might very well skew the results.
Yes, it might unblind the treatments, but the outcome would still be valid. I took part in a couple clinical trials, and I knew if I was treated or not. In one case I could not tolerate the med, and I dropped out (which removes me from the statistical analysis, preventing skew). In the other case, I knew that I was treated and continued treatment. The treatment worked, so even though I was "unblinded", my outcome was a valid measurement for inclusion in the statistical analysis.
>Why not use active placebos, like diphenhydramine or something with obvious anticholinergic effects.
That's a valid consideration, and more and more, active comparators are being used. An active comparator can also give some insight into methodological flaws. A recent study into the effectiveness of St. John's wort comes to mind (published in JAMA). The placebo response in this study was only 4.3%, whereas SJW response was over 14%. Despite a finding of a significant difference between the two groups (p > 0.02), the authors declared SJW ineffective. They did not, however, consider the low placebo response to be of any importance. An active comparator would have been a very important validator, in this case. There's something seriously wrong with an antidepressant trial obtaining only 4.3% placebo response.
> My opinion is not totally formed about this topic, and I try to keep an open mind (really!), despite my bad luck with them. But I am pretty convinced there are some major flaws in AD trials.
>
> Respectfully,
>
> MattThe biggest flaw is something you probably don't even consider: subject selection. More than 90% of the depressed population would be excluded from consideration as subjects in clinical studies, most often because of comorbid health conditions. How on Earth is one to extrapolate from an unrepresentative sample (simple uncomplicated depression) to the population at large (multiple health problems) if the latter group is excluded from study?
Posted by Larry Hoover on February 9, 2003, at 22:31:25
In reply to Placebo Responders Dropped? » Larry Hoover, posted by fachad on February 9, 2003, at 18:35:23
> > >During trials, apparently they give placebos first, then eliminate those test subjects who are affected by the placebos, thus sever3ely skewing the results.
> >
> > That's simply not true. That would not be double-blind.
>
> I'm sure I've read many studies where early responders, whether responding to the active agent, or the control, or the placebo, are dropped from the study.
>
> This is supposed to make the results more valid, by eliminating placebo responders so that all the results are from actual drug effects, vs. placebo response.It would certainly enhance the statistical significance, but I cannot think of an acceptable rationale for doing so. Post hoc data selection is nothing more than falsifying outcomes, in my mind. Do you have any kind of reference or example? I can't think of a case, myself.
The only post hoc selection process that I can think of off the cuff is called intention-to-treat analysis, but it actually makes it harder to obtain statistically significant results, not easier.
Posted by Larry Hoover on February 10, 2003, at 8:21:51
In reply to Placebo Responders Dropped? » Larry Hoover, posted by fachad on February 9, 2003, at 18:35:23
> > >During trials, apparently they give placebos first, then eliminate those test subjects who are affected by the placebos, thus sever3ely skewing the results.
> >
> > That's simply not true. That would not be double-blind.
>
> I'm sure I've read many studies where early responders, whether responding to the active agent, or the control, or the placebo, are dropped from the study.
>
> This is supposed to make the results more valid, by eliminating placebo responders so that all the results are from actual drug effects, vs. placebo response.
>It took me a while to find the right keywords to use..."run-in period" turns out to be the winner.
It makes a great deal of difference how one defines the methodology. Employing a run-in period in your design is an a priori tool, i.e. a decision made before study data is collected. As such, it is presumed to be without bias. What I thought I was hearing about was a post hoc decision, one made after data collection to "weed out" subjects who dilute the treatment effect.
In medical circles, there is a concern that run-ins are applied for the right reasons. Excluding non-compliers makes good sense, because you're only interested in people who can follow the protocol. However, I see no valid argument that the technique should be used to screen out placebo-responders and I still believe that such a tactic would represent bias and invalidate the study outcome. Employing a run-in definitely distorts the information provided by the study: "Compared with results that would have been observed without the run-in period, the reported results overestimate the benefits and underestimate the risks of treatment, underestimate the number needed to treat, and yield a smaller P value." (from the first abstract)
In a variant which combines a run-in to screen out placebo-responders, only non-placebo-responders are then assigned to one of two active comparator treatments. I can accept *that* practise. Anyway, here are some abstracts. The third one addresses the need for placebo-controlled studies in general (and makes a very good point, I might add).
JAMA 1998 Jan 21;279(3):222-5Comment in:
JAMA. 1998 May 20;279(19):1526-7.
JAMA. 1998 May 20;279(19):1526; discussion 1527.
JAMA. 1998 May 20;279(19):1526; discussion 1527.Run-in periods in randomized trials: implications for the application of results in clinical practice.
Pablos-Mendez A, Barr RG, Shea S.
Division of General Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032-3702, USA.
Prerandomization run-in periods are being used to select or exclude patients in an increasing number of clinical trials, but the implications of run-in periods for interpreting the results of clinical trials and applying these results in clinical practice have not been systematically examined. We analyzed illustrative examples of reports of clinical trials in which run-in periods were used to exclude noncompliant subjects, placebo responders, or subjects who could not tolerate or did not respond to active drug. The Physicians' Health Study exemplifies the use of a prerandomization run-in period to exclude subjects who are nonadherent, while recent trials of tacrine for Alzheimer disease and carvedilol for congestive heart failure typify the use of run-in periods to exclude patients who do not tolerate or do not respond to the study drug. The reported results of these studies are valid. However, because the reported results apply to subgroups of patients who cannot be defined readily based on demographic or clinical characteristics, the applicability of the results in clinical practice is diluted. Compared with results that would have been observed without the run-in period, the reported results overestimate the benefits and underestimate the risks of treatment, underestimate the number needed to treat, and yield a smaller P value. The Cardiac Arrhythmia Suppression Trial exemplifies the use of an active-drug run-in period that enhances clinical applicability by selecting a group of study subjects who closely resembled patients undergoing active clinical management for this problem. Run-in periods can dilute or enhance the clinical applicability of the results of a clinical trial, depending on the patient group to whom the results will be applied. Reports of clinical trials using run-in periods should indicate how this aspect of their design affects the application of the results to clinical practice.
Stat Med 1993 Jan 30;12(2):111-28A comprehensive algorithm for determining whether a run-in strategy will be a cost-effective design modification in a randomized clinical trial.
Schechtman KB, Gordon ME.
Washington University School of Medicine, Division of Biostatistics, St. Louis, MO 63110.
In randomized clinical trials, poor compliance and treatment intolerance lead to reduced between-group differences, increased sample size requirements, and increased cost. A run-in strategy is intended to reduce these problems. In this paper, we develop a comprehensive set of measures specifically sensitive to the effect of a run-in on cost and sample size requirements, both before and after randomization. Using these measures, we describe a step-by-step algorithm through which one can estimate the cost-effectiveness of a potential run-in. Because the cost-effectiveness of a run-in is partly mediated by its effect on sample size, we begin by discussing the likely impact of a planned run-in on the required number of randomized, eligible, and screened subjects. Run-in strategies are most likely to be cost-effective when: (1) per patient costs during the post-randomization as compared to the screening period are high; (2) poor compliance is associated with a substantial reduction in response to treatment; (3) the number of screened patients needed to identify a single eligible patient is small; (4) the run-in is inexpensive; (5) for most patients, the run-in compliance status is maintained following randomization and, most importantly, (6) many subjects excluded by the run-in are treatment intolerant or non-compliant to the extent that we expect little or no treatment response. Our analysis suggests that conditions for the cost-effectiveness of run-in strategies are stringent. In particular, if the only purpose of a run-in is to exclude ordinary partial compliers, the run-in will frequently add to the cost of the trial. Often, the cost-effectiveness of a run-in requires that one can identify and exclude a substantial number of treatment intolerant or otherwise unresponsive subjects.
Clin Ther 2001 Apr;23(4):596-603
Can placebo controls reduce the number of nonresponders in clinical trials? A power-analytic perspective.Leon AC.
Department of Psychiatry, Weill Medical College of Cornell University, New York, New York 10021, USA. acleon@mail.med.cornell.edu
BACKGROUND: There is ongoing debate regarding the ethics of placebo-controlled clinical trials when a moderately effective standard treatment exists. One aspect of the debate--the number of nonresponders--tends to be overlooked. A larger between-group effect size is expected in placebo-controlled trials than in trials with an active comparator. For that reason, substantially fewer subjects need to be enrolled in placebo-controlled trials; consequently, there tend to be far fewer nonresponders in placebo-controlled trials. OBJECTIVE: This analysis was undertaken to illustrate that the use of placebo as a control can reduce the number of subjects who are unnecessarily exposed to delayed treatment. METHODS: Statistical power analyses were used to estimate the sample size required to detect various population treatment differences and the resulting number of nonresponders for 2-tailed chi-square tests. RESULTS: Empiric evidence of the phenomenon is provided for a wide range of rates of response to placebo, investigational, and comparator treatments. For example, 24 subjects (ie, 12 per group) are needed to detect differences between placebo (10% response rate) and an investigational drug (70% response); 15 of these would not respond. In contrast, if the investigational drug (70% response) is initially compared with a standard therapy (60% response), 752 subjects would be required, 263 of whom would not respond. CONCLUSIONS: This paper shows empirically that placebo controls can reduce the number of nonresponders in a randomized controlled trial. The number of subjects who are exposed to unproven, albeit promising, investigational drugs should be kept to a minimum until placebo-controlled trials support their use.
Posted by linkadge on February 10, 2003, at 14:13:10
In reply to Re: Placebo Responders Dropped...abstracts, posted by Larry Hoover on February 10, 2003, at 8:21:51
Often critics notice the close similarity between placebo responce and drug responce in the short term. I think that in depression,
the placebo responce is higher than in other illnesses. Some people respond more to the
care and kindness they are shown during the trial. Where critics often turn a blind eye
is in the longer run, where the placebo people
often relapse. To those of us on this board, there is no question that these drugs help.
Often critics don't like the idea of well-being in a pill. Well studied research shows repeated results in favor of the drugs.Thats not to say they work for everyone - in your case there may be an undetermined chemical
in defecit. Just because they don't work for all doesn't mean they don't work for some.Linkadge
Posted by mattdds on February 10, 2003, at 15:20:51
In reply to Re: Placebo Responders Dropped...abstracts, posted by linkadge on February 10, 2003, at 14:13:10
>Often critics don't like the idea of well-being in a pill
You are beating up a straw man here. I don't think anyone implied that. Certainly the idea of curing mental illness with a pill appeals to me, which is why I tried so damn many AD's! Your argument distracts from the real issue, which is their efficacy, which in my opinion is not at all that well-founded, as you imply.
>To those of us on this board, there is no question that these drugs help.Who is "we"? Am I not someone who posts on this board as well? I certainly have not seen that everyone on this board is in agreement about AD's working well. Much to the contrary, I see evidence of the drugs not working for at least 50% of those taking them.
>Where critics often turn a blind eye
is in the longer run, where the placebo people
often relapse.When they do work, there is "poop out", which apparently did not occur to you. I have read countless posts on this board that go something like, "Help! Celexa poop-out!", or something like that.
You are quite right that these meds help some people. All I am saying is that placebos do too! If you gave placebo to 1000 patients with depression, you would get 300-500 of them saying that it worked. Imagine, 300-500 success stories of people raving about how much 10mg of sucrose miraculously changed their lives!
I think that we need more research on what the placebo effect is. In my opinion (that's all this is by the way, an opinion), that is where the bulk of antidepressant response is coming from.
Again, I don't claim to have all the answers. And I certainly don't have any "special" knowledge. I could very well be wrong. Maybe AD's do work on some level. I'm just not personally convinced. I am just revoicing some questions about this, that I don't feel have been answered yet.
Best,
Matt
Posted by Carlos C on February 12, 2003, at 2:14:41
In reply to Re: Placebo Responders Dropped...abstracts, posted by mattdds on February 10, 2003, at 15:20:51
I agree for the most part with Matt.
Larry Hoover sounds like a rep. for Eli Lilly. (or any other of the multi-billion dollar a year anti-depressant market.)
Posted by viridis on February 12, 2003, at 2:23:51
In reply to Re: Placebo Responders Dropped...abstracts, posted by Carlos C on February 12, 2003, at 2:14:41
How in the world did you draw that conclusion re: Larry H.? He's got to be one of the most unbiased, objective posters here, in my opinion (and also one of the best-informed).
Posted by mattdds on February 12, 2003, at 15:20:20
In reply to Re: Placebo Responders Dropped...abstracts » Carlos C, posted by viridis on February 12, 2003, at 2:23:51
Carlos,
I think I'm with Viridis on this one, Larry H is definitely unbiased and open-minded. Not to mention probably the most well read on this board. He, like me, probably hasn't made up his mind completely about AD's, as this is a complex subject. I got something totally different from what he was saying. Keep posting!
Best wishes,
Matt
Posted by Larry Hoover on February 12, 2003, at 22:40:03
In reply to Re: Placebo Responders Dropped...abstracts, posted by Carlos C on February 12, 2003, at 2:14:41
> I agree for the most part with Matt.
>
> Larry Hoover sounds like a rep. for Eli Lilly. (or any other of the multi-billion dollar a year anti-depressant market.)I'm a little surprised at that. I'd be happy to answer any questions you might have. I'm a scientist, but I don't have any connection to Big Pharma.
Lar
Posted by Carlos C on February 13, 2003, at 2:30:49
In reply to Re: Placebo Responders Dropped...abstracts » Carlos C, posted by Larry Hoover on February 12, 2003, at 22:40:03
> > I agree for the most part with Matt.
> >
> > Larry Hoover sounds like a rep. for Eli Lilly. (or any other of the multi-billion dollar a year anti-depressant market.)
>
> I'm a little surprised at that. I'd be happy to answer any questions you might have. I'm a scientist, but I don't have any connection to Big Pharma.
>
> Lar
>I appologize if I have offended anyone. I admit I made a quick assesment.
Larry,
you just seemed to always have something contrary to Dan's every finding. I felt as though in every case you pushed hard to stand so strongly for SSRI's. I suppose I should take into account the sole porpuse of disscussion and be glad it remained civil.Once again my appologies,
Carlos
Posted by Larry Hoover on February 13, 2003, at 10:41:49
In reply to Re: Placebo Responders Dropped...abstracts, posted by Carlos C on February 13, 2003, at 2:30:49
> I appologize if I have offended anyone. I admit I made a quick assesment.
I certainly didn't take offense. I see no reason to apologize, but I'll accept one anyway. <wink>
> Larry,
> you just seemed to always have something contrary to Dan's every finding. I felt as though in every case you pushed hard to stand so strongly for SSRI's.I was discussing methodology (I thought). One of the things I do professionally is assess other people's methodology (although not in the medical field, which has different rules for human subjects). You'd never see a run-in period using rats, for example.
>I suppose I should take into account the sole porpuse of disscussion and be glad it remained civil.
That's one of the things I most like about this forum, the requirement for civil discourse. <Thanks, Bob.>
> Once again my appologies,
>
> CarlosI welcome challenges to my thinking, Carlos. That's the only time I can learn. Challenge me any time you want, OK?
Lar
Posted by mattdds on February 13, 2003, at 11:25:06
In reply to Re: Placebo Responders Dropped...abstracts, posted by Carlos C on February 13, 2003, at 2:30:49
Gentlemen,
Great discussion. I am impressed at how everyone maintained their cool on this controversial subject. I sure learned a lot. It is encouraging that we can talk about these things without anyone getting too dogmatic about their opinions. I think this attitude is much more productive.
Thanks,
Matt
Posted by IsoM on February 13, 2003, at 13:19:16
In reply to Re: Placebo Responders Dropped...abstracts » Carlos C, posted by Larry Hoover on February 13, 2003, at 10:41:49
Larry, I'm posting here instead of the CLA link but it's to do with the abstracts on CLA. You mentioned that lab produced CLAs would have a higher proportion of c9t11-CLA & t10c12-CLA as opposed to what occurs naturally in the fat of ruminants.
But in the abstracts, when studies were done on possible benefits, what CLAs were used for these studies? It seems to imply that the man-made isomer mixes were used, not extracts from the fat of the ruminants. I found quite a few more abstracts on CLAs but in all of them, it implies or directly states that the CLAs used were the supplemental ones sold. Do you want to clarify anything about this as I'm curious to what was used & how that would compare to the actual fat of grass-grazed ruminants. Does that change any of the results of the studies & what they'd be like if actual fat was used instead?
Got a few more questions -
1. The newer methods that labs use now to separate racemic mixtures in lab synthesized compounds (like thalidomide) - can these methods (or similar ones) be used in separating isomers of fatty acids? And if they can be used, are they actually in use or is the method still prohibitory expensive?2. What exactly is done in the labs to ordinary sunflower oil (or other polyunsaturated ones) to make CLAs? What's the method?
3. Considering what's done with the excess of beef tallow in the food industry, would it be feasible for labs to extract the CLAs from beef fat rather than synthesize it from vegetable oils?
4. As I said earlier, I prefer to get mine from real food, but is the high price of CLA supplements justified by the cost of production?
5. Is there much difference that you know of in the fatty acids of pork & chicken fat between those factory produced animals & those raised "free range"? I know the fatty acids of eggs show a difference. I'm curious as pork & chicken fat is much less solid than beef & sheep (lamb) fat at room temperature.
6. And finally - the values used in the USDA sites of nutrient breakdown - these would all be the averages, I assume, so they'd be the values of factory produced animals. Am I correct?
As an extra for you about taurine - I wondered why cat food needs to have taurine added to the food. I knew that cats have a higher requirement of taurine than most animals. If it had to be added, I wondered where they would've got it from before pet foods had it added. Did some checking & comparing, & found some of the highest levels of taurine are found in rodents. If I wouldn't be grossed out skinning the little beggars, I'd add them to the meat mix I use in making my cats' home-made food. I'm not at all squeamish but that's going a bit too far. I buy it as a powder & add it instead.
This is the end of the thread.
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