![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 51 to 75 of 78. Go back in thread:
Posted by linkadge on December 14, 2005, at 22:17:10
In reply to Tracy, Breggin, and other quacks..., posted by gibber on December 11, 2005, at 21:47:35
There was a time too when I would sit and defend any allegations made against the precious class of drugs.
But the more people I talk to, and the more information I read has made me cautious of anyone who referes to the drugs as wonder drugs, and who pays no attention to some of the studies that come out.
Med-Empowered and I were refering the other day to some of the studies that showed how mice exposed to SSRI's for exended periods of time developed "corkscrewed" serotonin receptors.
This is one of the studies refered to by Breggin.
People like to call him a quack, because if the studies he referrs to are true than that changes a lot.
A psychiatrist may infact believe the study and yet still not tell you this, mainly because he thinks its in your best interest not to know.
Referring to Breggin as a "quack" makes life easier...... for the time being
whoa ha ha ha ha ha ha ha ha ha......(sorry)
Linkadge
Posted by Emme on December 14, 2005, at 22:28:44
In reply to Re: What!, posted by linkadge on December 14, 2005, at 20:33:23
Hi Link,
Just a quick 2 cents on one particular point.
> Current antidepressants reduce depression, and anxiety by creating emotional indifference.
Ain't necessarily so! At least not in my personal experience. Yes, Lexapro definitely numbed me out. But when I had positive responses to Paxil and to Wellbutrin + Serzone, my emotions felt very much alive and I was able to experience pleasure again. And I still experienced some anxiety, but it was an *appropriate* amount of anxiety instead of being over the top. Like some nervousness for giving a talk, but not enough to be a real problem. So yeah, I think it's possible for ADs to work without turning you into a zombie.
emme
Posted by linkadge on December 14, 2005, at 22:37:29
In reply to Gullibility, posted by jamestheyonger on December 11, 2005, at 23:12:30
Listen folks. All I am saying is that the issue is not binary.
We want the information to be binary because it makes us feel confident about our decisions.
Take depakote.
It may help your mood. But it is a fact that it may damage your liver. It is a fact that my mother has a bad liver from years of depakote use.
There are some real dangers that may be associated with the use of certain drugs. That is a fact, not psudoscience. Just like antipsychotics can dammage certain areas of the brain. That is a fact. Psychiatrists know that. It's not just the Tom Cruises.
I am under the belief that a lot of information/dangers are withheald / played down because it is percieved that the best interest of the mentally ill.
It is not a black and white issue. I don't know why people try to make it into that.
Linkadge
Posted by linkadge on December 14, 2005, at 22:43:12
In reply to Re: What! » linkadge, posted by Emme on December 14, 2005, at 22:28:44
Ok. Its not true with every drug. But it seems that often SSRi's helped just by numbing me.
Linkadge
Posted by Larry Hoover on December 14, 2005, at 22:55:52
In reply to Re: What!, posted by linkadge on December 14, 2005, at 20:33:23
> I don't think that a net reduction has been *clearly* demonstrated at all.
Like I said before, I like to let the facts speak for themselves. I'm an empiricist. This is one of the most convincing studies I've come across, in years. The source data are completely independent (collected for other legitimate but reliable purposes) and show highly significant statistical relationships.
Arch Gen Psychiatry. 2003 Oct;60(10):978-82.
Relationship between antidepressant medication treatment and suicide in adolescents.Olfson M, Shaffer D, Marcus SC, Greenberg T.
Department of Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons of Columbia University, New York 10032, USA. olfsonm@child.cpmc.columbia.edu
CONTEXT: A decade of increasing antidepressant medication treatment for adolescents and corresponding declines in suicide rates raise the possibility that antidepressants have helped prevent youth suicide. OBJECTIVE: To evaluate the relationship between regional changes in antidepressant medication treatment and suicide in adolescents from 1990 to 2000. DESIGN: Analysis of prescription data from the nation's largest pharmacy benefit management organization, national suicide mortality files, regional sociodemographic data from the 1990 and 2000 US Census, and regional data on physicians per capita. PARTICIPANTS: Youth aged 10 to 19 years who filled a prescription for antidepressant medication and same-aged completed suicides from 588 three-digit ZIP code regions in the United States. MAIN OUTCOME MEASURES: The relationship between regional change in antidepressant medication treatment and suicide rate stratified by sex, age group, regional median income, and regional racial composition. RESULTS: There was a significant adjusted negative relationship between regional change in antidepressant medication treatment and suicide during the study period. A 1% increase in adolescent use of antidepressants was associated with a decrease of 0.23 suicide per 100 000 adolescents per year (beta = -.023, t = -5.14, P<.001). In stratified adjusted analyses, significant inverse relationships were present among males (beta = -.032, t = -3.81, P<.001), youth aged 15 to 19 years (beta = -.029, t = -3.43, P<.001), and regions with lower family median incomes (beta = -.023, t = -3.73, P<.001). CONCLUSIONS: An inverse relationship between regional change in use of antidepressants and suicide raises the possibility of a role for using antidepressant treatment in youth suicide prevention efforts, especially for males, older adolescents, and adolescents who reside in lower-income regions.
> That is what has been argued for the past however many years.It's been argued, but from smaller samples. Type 1 error is the biggest issue for scientists to manage.
> Many authors have come to the conclusion that no such reduction has been demonstrated.
>
> http://biopsychiatry.com/suicide.htmlOr, there's this study, demonstrating a significant change in slope of the suicide rate coinciding with the introduction of SSRI meds. The only way to get a change in slope as described in this study is to have a change in the independent variable(s). It would be a big coincidence if it wasn't related to the introduction of SSRIs.
Pharmacoepidemiol Drug Saf. 2001 Oct-Nov;10(6):525-30.
Antidepressant medication and suicide in Sweden.
Carlsten A, Waern M, Ekedahl A, Ranstam J.
Department of Social Medicine, University of Goteborg, Sweden. anders.carlsten@telia.com
OBJECTIVE: To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups. METHODS: A time series analysis using a two-slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs. RESULTS: Antidepressant sales increased between 1977-1979 and 1995-1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 10(5) inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990-1997. Half of these 'saved lives' occurred among young adults. CONCLUSION: We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales.
> There also exist studies that show the course of depression to be worsened by antidepressant use.True. But when large studies were done, as were just recently published, there is no such signal. You have to consider Type 1 error.
> Current antidepressants reduce depression, and anxiety by creating emotional indifference.
That's one possible outcome.
> The frontal lobe syndrome caused by SSRi's serves to disinhibit the user, making them more prone to impulsive behavior.
What is this frontal lobe syndrome?
> I don't doubt for a minaute that antidepressants can increase the likeyhood of suicide.
There is a brief increase in suicidal risk from SSRIs. When compared to that induction caused by tricyclics, it is a smaller risk. What has happened is that the SSRIs are getting bad press, that tricyclics, for example, never faced.
> Dr. Tracy made a good point. The drug companies pay.
>
>
> LinkadgeThat's where I disagree absolutely. Antidepressants are tools. When those tools are not properly managed, I would focus on the mismanagement. The idea that a potentially suicidal depressed patient is written a prescription for one of these drugs, and told to come back in three months (or whatever), is where the problem lies. Proper medical management requires much more than that. E.g. explicit warnings to the patient, to immediately report certain specific adverse effects; frequent reassessments by trained medical personnel; involvement of the family or close friends of the patient, for monitoring purposes; brief prescriptions initially, until the patient's response can be assessed.....so much more can be done, to make the use of these drugs safe.
The medications in question are powerful, complicated, and somewhat unpredictable. The treated patients are not inherently stable at the time of treatment. Complacency in management of these medications is the primary flaw, IMHO.
Lar
Posted by linkadge on December 14, 2005, at 23:48:14
In reply to Re: What! » linkadge, posted by Larry Hoover on December 14, 2005, at 22:55:52
I see no significant relationship.
I quote from a study in the Archives of General Psychiatry of all U.S. suicides between 96-98.
http://archpsyc.ama-assn.org/cgi/content/abstract/62/2/165
"The overall relationship between antidepressant medication prescription and suicide rate was not significant."
Most psychiatrists agree that the only agents that have demonstrated a clear effect on suicidiality are lithium and clozapine.
>It's been argued, but from smaller samples. Type >1 error is the biggest issue for scientists to >manage.
I don't see anything conclusive here.
Many of the Brittish records show an increased rate of suicide for during start up, but then little to no effect aftarwards.
>True. But when large studies were done, as were >just recently published, there is no such >signal. You have to consider Type 1 error.
No, I am referring to the whole course of the illness. Ie, how without antidepressants, most people recover from depression 8mos to a year. Some studies show that with treatement, it actually becomes a more chronic disorder.
>What is this frontal lobe syndrome?
http://www.antidepressantsfacts.com/frontal-lobe-syndrome.htm
>That's where I disagree absolutely. >Antidepressants are tools. When those tools are >not properly managed, I would focus on the >mismanagement. The idea that a potentially >suicidal depressed patient is written a >prescription for one of these drugs, and told to >come back in three months (or whatever), is >where the problem lies. Proper medical >management requires much more than that. E.g. >explicit warnings to the patient, to immediately >report certain specific adverse effects; >frequent reassessments by trained medical >personnel; involvement of the family or close >friends of the patient, for monitoring purposes; >brief prescriptions initially, until the >patient's response can be assessed.....so much >more can be done, to make the use of these drugs >safe.Even when the tools are used properly, bad things can happen. I am an example. I used the drugs properly.
>The medications in question are powerful, >complicated, and somewhat unpredictable. The >treated patients are not inherently stable at >the time of treatment. Complacency in management >of these medications is the primary flaw, IMHO.No arguments.
Posted by Larry Hoover on December 15, 2005, at 0:21:20
In reply to Re: Dr. Tracy on SSRIs.., posted by linkadge on December 14, 2005, at 22:05:08
> >We're arguing a semantic distinction, about our >interpretation of another person's words
> >Localized serotinergic activation can be, on a >relative scale, high or low. I am arguing >against a global "elevated serotonin" state, as >postulated by the under-educated Tracy.
>
> I see you did not read the link that I put up.I read it. There was no evidence presented that the pre-synaptic neuron would release identical amounts of serotonin under both transporter conditions, nor any evidence presented that COMT or MAO-A concentrations were the same.
> The state that SSRI's induce would be very similar to that of an individual who posesses the double short varient of the serotonin transporter gene.
There is no evidence to reach that conclusion. It is a conceivable hypothesis, but it has never been tested.
The only easily tested hypothesis which arises from this heterogeneity of SERT promoter regions is to determine if SSRI response is different under the three natural populations. It may well explain why SSRIs don't work for everybody. Or part of the why.
> Dr. Tracy argues that SSRI's cause depression and suicide.
SSRIs are depressogenic?
Suicide rates are falling.
http://www.afsp.org/statistics/USA.htmThere is one drug with extremely powerful suicidal potentiation. Alcohol. I won't waste space here, but I have all kinds of data on that.
There is no autopsy evidence for SSRI potentiation of suicide. But alcohol? Huge. Widely available, without a prescription.
> This link that I put up is research showing how lifetime depressive episodes correlate with the serotonin transporter gene. This research supports her theory that taking an SSRI (and thus lowering SERT activity) could cause depression, alcoholism etc.
No, it doesn't. It links a homozygous gene to those events. Not SSRIs.
>
> >We can mess with the brain, with drugs, and >produce unnatural states. Tracy was implying an >innate condition, "excess serotonin", or however >she phrased it, was the underlying etiological >factor in mental diseases of all sorts.
>
> That may be. If we discovered the antidepressant effects of Tianeptine beofore that of SSRI's we might have the same hypothesis.Or Tianeptine might work on homozygous short-short SERTs?
I strongly reiterate. There is no pathological excess serotonin state.
> >Whether that's your theory or hers, I disagree. >I don't think anyone knows the mechanism, but it >most certainly won't be as simple as that.
>
> Many doctors think that the rem sleep depriving mechanisms are key force in their behavioral effects. Quite a few agents (for instance Surmontil) which have no effect on monoamine uptake, but do reduce REM sleep, are effective antidepressants.In so many words, it's like trying to construct a platypus. These pieces, these analogies, do no demonstrate that SSRIs do or do not do similar things. Those are untested hypotheses. Having an hypothesis is proof of nothing. Tracy would have you believing her theory because of plausibility of its constituent hypotheses.
> >It's a meaningless phrase. That's my point. It >contributes nothing, except perhaps, hooking the >naive mind.
>
> If any drug were capable of mimicing some the catastrophic alterations in cognition an sentience that are evident in old age, I'd like to know about it. For instance, smoking will age you prematurely. Knowing that is not meaningless.Getting back to how this phrase came into our discussion, Tracy claims that this "excess serotonin" state causes premature aging. You seem to have just contradicted that, quite explicitly.
>
>
> >Which differs so substantially across the >population it is more reasonably a genetic trait >(susceptibility) than a drug effect.
>
> I was not the first one to suggest the connection between the subjective effects of antidpressants and LSD. Many experienced LSD users have likened the effects of LSD to antidepressants. Studies show that fluoxetine potentiates the discrimintive stimulus effects of LSD.
>
> See the abstract at:
>
> http://www.antidepressantsfacts.com/prozac-lsd.htmNo, not potentiation. "...all data were compatible with additivity of effects rather than true potentiation."
Like alcohol and benzos.
> These reports are more than just coincidences. There are biochemical reasons that the drugs can produce similar states of mind. And that is important information, when faced with the task of sorting out some of the behavioral states that have been linked to SSRI use.
>
> >I am an outlier. Me. I've had very bizarre drug >effects, when compared to normalized data. My >bizarre response to a drug demonstrates nothing,
> >other than I should avoid the drug.
>
> But we are talking about experiences that have happened to more than just one person. We are also talking about experiences that may be partially explained by studies like the one above which show how these two agents can produce similar behavioral states.The one above was about dogs. I wonder just what the dogs said to describe their experiences.
And, individual idiosyncratic reactions happen all the time. Read almost any monograph. "People with sensitivity to X class substances should not use this medication.", or such like. It's not an indictment of the drug. Or even the class of drugs. It's about being responsible about what you ingest.
> >She wants to blame the drug for all aberrant >behaviour. And I'm still waiting for the >explanation part.
>
> And I am still waiting for the explaination for how antidepressants actually help depression.How? Who the heck knows that?
> Since there is not much of a solid theory for that, I can't pick too many holes in arguing the
> negation.That's what I meant earlier about mechanistic arguments. They really are pointless.
Native peoples used to make a special tea from twigs of red willow, to relieve pain. Following a traditional prayer and invocation, the medicine man would administer the decoction, believing that he had facilitated the transfer of the willow spirit to the afflicted party. Often, the pain went away.
Other people, with different beliefs, discovered salicylic acid in willow bark, derived a synthetic form, and made a near-bankrupt German dye chemist named Bayer very rich.
Both were effective treatments, with entirely different mechanisms.
> >Her generalizations amount to hyperbole without >any reasonable support.
>
> Hyperbole without any reasonable support? We've got two drugs. One inhibits the reuptake of serotonin, and the other increases the uptake of serotonin. Both are "effective antidepressants".That's not hyperbole. And we don't know why. But we do know that they work. Empirical evidence.
> Vitamin C either prevents scurvey, cures scurvey, or neither.
In different circumstances, each phrase is true.
>
> >That is false, bizarre, fear-mongering, >meaningless.
>
> Fear mongering, maybe. I see it as a necessary counterballence, in a world of "pop this".How about promoting better medical management. More personal interaction with caregivers. Providing critical information for true informed consent. No fear-mongering required.
> After 8 months off of 100mg of zoloft, I am still relearning how to walk properly.
I'm sorry that is true for you. I must resort to logical analysis. Post hoc ergo propter hoc is a fallacious interpretation, a good part of the time.
You may have other medical concerns.
> >Oh, but you snipped the part about "the gummy >gooey glossy substance". I thought that was so >relevant.
>
> Like I said. I don't agree with everything she says. But I do agree with her main argument that SSRI's can sometimes induce abnormal and frankly dangerous states of mind.Sometimes, they do. And if appropriate precautions had been taken, and corrective action initiated at the first sign of trouble, I think that many of the most serious outcomes would simply never have happened.
When Szasz et al emptied the asylums, the enabling belief that permitted such a drastic change in medical management was that medication alone would suffice. But, what inevitably also happened was that contact with caregivers was totally disrupted. And this idea, that medicine through pharmacepia had reached a golden age, enveloped the entire culture. I remember Prozac hitting the front cover of Time magazine. I still have it, somewhere. Pure propaganda. Everyone bought into it. But nobody wants to take responsibility for it. That's how the Holocaust came about.
> >This woman makes what amount to emotional >appeals. Her theories contain vague expressions >which can be taken in many ways. There is a >plausibilty to what she says. But nowhere, does >she offer the data, the observations, the >physical evidence, to support even her core >allegations. What baby?
>
> Thats not true. For example, she talks about how the worker for Lilly ended up resigning due to her decision to make a firm stance against the safety of SSRI's.I didn't listen to the whole interview.
> She also referres to studies in which patients given SSRI's reported increased hostility and suicidal behavior.I have read through some of the complete clinical trial data for some of the SSRIs. We're talking reports of over 500 pages. The raw data. And I'm convinced, just as the recent task force was convinced, that methodological deficiencies in many studies are so profound, that concluding anything about suicidal induction during the studies is questionable. The studies were not designed to collect that sort of information. The way the information was extracted from the raw data was flawed. In one study I analyzed, which suggested a six-fold increase in suicidality in adolescents using Paxil, the detailed analysis revealed that there were no suicidal gestures attributable to Paxil, and the only true suicidal act was in the placebo group. If you want to see that, I'll dig it up and show it to you.
> If forget her name, but she referred to one of the key scientists who was involved in the idenficiation of the serotonin reuptake mechanism, who referred to the SSRI's as monster drugs. These are real people, with real credability who agree with her on different levels.I have no problems with people holding different opinions. I have problems with people making unfounded allegations, i.e. those without underlying evidence. I'm an empiricist. The data are the only truth we have. All else is interpretation.
> >As I said earlier, let the data speak for >themselves.
>
> Let it.Good. Agreed there.
> >No, not that I've seen.
>
> Ok, maybe not the exact same things. But ther "are" very intellegent people who do not agree that these drugs cary the safety that is assumed by most doctors. There are intellegent people who believe that the drugs can induce suicidal thinking and behavior. Do you want to know who some of these people are?Link, I have very closely followed the research. I read every study on this subject. The recent Healy and Martinez studies were rather compelling. If there is a suicidal signal, it is brief, early, and small. Medical management can handle these issues.
> There are scientist out there right now who are developing animal models of antidepressant induced mania and rapid cylcing. Some of this research is on www.neuransmitter.net. While Dr. Tracy is extreme. I don't thing she is out of the ballpark.
She's in the ballpark. She's the candy floss.
> >Would you kindly present her evidence? I've seen >none. I am totally serious.
>
> Well, for starters, she said that SSRI's can induce psychotic states. I mentioned above some information on researchers who are studing the propensity of SSRI's to induce mania.They can induce psychosis, yes. They can trigger mania, certainly.
> Researchers create links between some of the genes affected by stimulants, and antidepressants, to try and sort out some of the findings. These are obviously *very expensive* studies to undertake, and would not be done if there was indeed "no evidence"
I was meaning her evidence. Her hypotheses are not directly connected to evidence. I'm being generous. Myrrh oil? All mental illness is sugar related? (or something like that)
> >Perhaps we should agree to disagree?
>
> I am happy with anyone who agrees that the safety of SSRI's is not a closed case.
>
> LinkadgeIt's far from closed. And I am not trying to shut the door. I'm trying to lay a solid foundation of empirical evidence, and put to rest hyperbole and fear-mongering.
Lar
Posted by Larry Hoover on December 15, 2005, at 0:34:45
In reply to Re: Tracy, Breggin, and other quacks..., posted by linkadge on December 14, 2005, at 22:17:10
> Med-Empowered and I were refering the other day to some of the studies that showed how mice exposed to SSRI's for exended periods of time developed "corkscrewed" serotonin receptors.
Do you have any idea of the doses used in that study? Off the top of my head, I think it was 360 times the maximum human dose, maintained for 12 weeks (equivalent to 15 years of a human life span). And I think the hypothalamic dendrites were corkscrewed, not the receptors. I don't recall for sure.
> This is one of the studies refered to by Breggin.Who should have known better to simply generalize to people taking the drug as prescribed. There are toxic thresholds. Novel effects that only occur at or above certain concentrations. These are called toxicoses. There is no reasonable extrapolation from that mouse experiment to any human experience conceivable.
> People like to call him a quack, because if the studies he referrs to are true than that changes a lot.
He's a quack because he cherry-picks quotations from studies, reports secondary and tertiary references as if they were primary, reports data out of context, and ignores the published conclusions of the study authors. He also has been shown to fabricate the odd bit of data.
> A psychiatrist may infact believe the study and yet still not tell you this, mainly because he thinks its in your best interest not to know.
That's an easy straw man argument to raise.
> Referring to Breggin as a "quack" makes life easier...... for the time beingBreggin likes to sell books. He does not do primary research. He "mines" other peoples work, and creates a collage. Breggin is better at it than Tracy. He actually knows better, but does it anyway.
> whoa ha ha ha ha ha ha ha ha ha......(sorry)
>
>
> LinkadgeIf you've got the time, you can take Breggin apart, too.
I'm amazed I stayed up to post these. Enough. G'nite.
Lar
Posted by Larry Hoover on December 15, 2005, at 1:51:46
In reply to Re: What!, posted by linkadge on December 14, 2005, at 23:48:14
> I see no significant relationship.
>
> I quote from a study in the Archives of General Psychiatry of all U.S. suicides between 96-98.Earlier work, before the issue was more fully examined. We're a decade past this report.
> http://archpsyc.ama-assn.org/cgi/content/abstract/62/2/165
>
> "The overall relationship between antidepressant medication prescription and suicide rate was not significant."Ahhh, but you fail to quote the following: "By contrast, increases in prescriptions for SSRIs and other new-generation non-SSRIs are associated with lower suicide rates both between and within counties over time and may reflect antidepressant efficacy, compliance, a better quality of mental health care, and low toxicity in the event of a suicide attempt by overdose."
It's the lumping together of TCA and newer antidepressants that gives a non-significant outcome. TCAs are themselves quite toxic, and are associated with a significantly higher rate of completion.
> Most psychiatrists agree that the only agents that have demonstrated a clear effect on suicidiality are lithium and clozapine.
That's not the case.
> >It's been argued, but from smaller samples. Type >1 error is the biggest issue for scientists to >manage.
>
> I don't see anything conclusive here.
>
> Many of the Brittish records show an increased rate of suicide for during start up, but then little to no effect aftarwards.By six months of treatment, there is no longer a signal. What that means is that suicide reduction has already cancelled any start up effect. From there on, it is straight reduction in suicidal frequency. The "start up" effect, or whatever you want to call it, is present with every antidepressant class, and always was. Actually, a little worse with TCAs. It's just that nobody talked about it.
> >True. But when large studies were done, as were >just recently published, there is no such >signal. You have to consider Type 1 error.
>
> No, I am referring to the whole course of the illness. Ie, how without antidepressants, most people recover from depression 8mos to a year. Some studies show that with treatement, it actually becomes a more chronic disorder.You've snipped so much of what I said, I have no idea what you're replying to.
In reply to your closing sentence, chronic recurrent depression is associated with more frequent treatment. Correlation is identical, when you invert the variables. Same magnitude, same direction.
Moreover, your thesis ignores the kindling effect. Aggressive medication protocols were developed precisely because of kindling.
> >What is this frontal lobe syndrome?
>
> http://www.antidepressantsfacts.com/frontal-lobe-syndrome.htmOnce again, a rare outcome, easily addressed by proper and thorough medical management of the treated patient. All five subjects had their adverse effects corrected with medical management. Not a drug problem. A management problem.
>
> >That's where I disagree absolutely. >Antidepressants are tools. When those tools are >not properly managed, I would focus on the >mismanagement. The idea that a potentially >suicidal depressed patient is written a >prescription for one of these drugs, and told to >come back in three months (or whatever), is >where the problem lies. Proper medical >management requires much more than that. E.g. >explicit warnings to the patient, to immediately >report certain specific adverse effects; >frequent reassessments by trained medical >personnel; involvement of the family or close >friends of the patient, for monitoring purposes; >brief prescriptions initially, until the >patient's response can be assessed.....so much >more can be done, to make the use of these drugs >safe.
> Even when the tools are used properly, bad things can happen. I am an example. I used the drugs properly.By properly, do you merely mean as prescribed? Were your adverse symptoms immediately reported, and addressed by changes in protocol, monitoring, and management?
>
> >The medications in question are powerful, >complicated, and somewhat unpredictable. The >treated patients are not inherently stable at >the time of treatment. Complacency in management >of these medications is the primary flaw, IMHO.
>
> No arguments.My thesis, in simple form. SSRI meds are not inherently injurious to patients. Poor outcomes and extreme adverse effects arise from the absence of: medical oversight and monitoring; true informed patient consent; lack of social supports during treatment; and, failure of the medical community to communicate with respect to the management challenges arising during treatment, to develop protocols for adverse events.
Tracy remains a quack, and a fraud for calling herself doctor.
Lar
Posted by linkadge on December 15, 2005, at 19:01:44
In reply to Re: Dr. Tracy on SSRIs.. » linkadge, posted by Larry Hoover on December 15, 2005, at 0:21:20
>I read it. There was no evidence presented that >the pre-synaptic neuron would release identical >amounts of serotonin under both transporter >conditions, nor any evidence presented that COMT >or MAO-A concentrations were the same.
But the point is that the level of the protein is reduced. If our theory of depression is that the *5-ht* reuptake mechanism is too active in depression, then this is information to suggest against it. Of course there could be compensatory changes in MAO-A, but this could also happen in patents treated with SSRI's.
>There is no evidence to reach that conclusion. >It is a conceivable hypothesis, but it has never >been tested.Scientists like to study one gene at a time. It makes sence to see if the 5-ht transporter is associated with depression or not. It's just like if you found low acetylcholinsterase in Alzeimer's disease, then it might make one rethink the model.
>The only easily tested hypothesis which arises >from this heterogeneity of SERT promoter regions >is to determine if SSRI response is different >under the three natural populations. It may well >explain why SSRIs don't work for everybody. Or >part of the why.One researcher found that individuals with the long varients of the transporter responded better to SSRI's than did those with the short varients.
>SSRIs are depressogenic?
Yes, I would argue that they can be for certain individuals. Mood may be maintained by a very delicate ballence between serotonin and dopamine. If you get too much serotonin, I think it can cause depression. I experienced a distinct worsening of all core symptoms of depression on paxil.
>Suicide rates are falling.
>http://www.afsp.org/statistics/USA.htmBut to associate this with SSRI use may not be accurate.
>There is no autopsy evidence for SSRI >potentiation of suicide. But alcohol? Huge. >Widely available, without a prescription.
I don't think that autopsy information is necessary.
>No, it doesn't. It links a homozygous gene to >those events. Not SSRIs.I realize that. It is not a direct link, but it is something that has really baffled a lot of researchers. I emailed Dave on www.biopsychiatry.com and asked him what he thought about the issue of the serotonin transporter, and some of the recent findings. He said to me, that sometimes in psychiartry you will find things that don't fit the mold. Sometimes the findings will seem to indicate the exact opposite.
SSRI's may *work* through a different mechanism alltogether. We have serotonin uptake inhibiting drugs that have no antidepressant potential whatsoever. All of the currently available SSRI's increase the activity of the gabaergic neurosteroid allopregnalone, some 20 fold.
>Or Tianeptine might work on homozygous short->short SERTs?
Well this is it. I was just more surprised by the fact that the study seemed to suggest that the most chronically depressed posessed the double short varient.
>I strongly reiterate. There is no pathological excess serotonin state.I strongly reiterate. Some researchers think that excessive serotonergic function in certain areas of the brain result in anxiety. There are researchers who believe that certain generalized anxiety disorders are due to elevated serotonin activity. Some think high serotonergic neurotransmission may be involved in anorexia.
http://www.mhsource.com/expert/exp1041502a.html
>Getting back to how this phrase came into our >discussion, Tracy claims that this "excess >serotonin" state causes premature aging. You >seem to have just contradicted that, quite >explicitly.I don't see what you mean. There are theories out there as to how SSRI's may advance aging. The melatonin theory sounds convincing. I can see how chronically lowering melatonin might acellerate aging. There are other theories too.
>No, not potentiation. "...all data were >compatible with additivity of effects rather >than true potentiation."The article says that fluoxetine substituted for LSD in certain paradigms.
>The one above was about dogs. I wonder just what >the dogs said to describe their experiences.
This is about findings that may confirm some of the experiences that people have had.
>And, individual idiosyncratic reactions happen >all the time.
It is not an idiosyncracy. Both agents potently stimulate certain sertonin receptors. We have no problem accepting that GI effects may be due to excess 5-ht3 stimulation, but yet cannot believe that people have had perceptual disturbances consistant with excess 5-ht2a agonism ?
There are some documented cases of antidepressant induced perception disorder on www.biopsychiatry.com in addition to expert explainations of the events.
>How? Who the heck knows that?Exactly. We can pop a pill based on unproven theory, yet we start wars in defence of drugs based on unproven theory. She is not the only one who has attacked the theory behind SSRI medications.
>That's what I meant earlier about mechanistic >arguments. They really are pointless.
So what good is it to say that she is devoid of proof, when we have no proof of the opposite. Her proof may be our lack of proof.
>Other people, with different beliefs, discovered >salicylic acid in willow bark, derived a >synthetic form, and made a near-bankrupt German >dye chemist named Bayer very rich.
True, but we later learned how aspirin causes more deaths each year than any other drug (I believe). I am not going to try and dismiss the information that points to the dangers of aspirin.
>That's not hyperbole.
Did I say it was ?
>And we don't know why. But we do know that they >work. Empirical evidence.
It is a truth that the drug company can still market a drug when only 1/8 of the studies show any benefit.
>How about promoting better medical management. >More personal interaction with caregivers. >Providing critical information for true informed >consent. No fear-mongering required.Fair enough.
>Post hoc ergo propter hoc is a fallacious >interpretation, a good part of the time.
>You may have other medical concerns.I'm sorry I brought it up. I didn't know you were going to be one of those people.
>Sometimes, they do. And if appropriate >precautions had been taken, and corrective >action initiated at the first sign of trouble, I >think that many of the most serious outcomes >would simply never have happened.
For certain individuals, the kind of monitoring necessary is not tangable. Monitoring cannot prevent all potential problems. Monitoring cannot prevent T.D. for instance, with neuroleptic use.
>I didn't listen to the whole interview.
I know
>I have read through some of the complete >clinical trial data for some of the SSRIs.
..
>If you want to see that, I'll dig it up and show >it to you.You are one individual. Other individuals have analayed similar data, and have come to different conclusions.
>All else is interpretation.
Thats the problem. The argument in support of these drugs is interpretation. The mechanisms are theoretical. When you don't know why they work, and why they fail, then interpretation becomes more tangable.
>Link, I have very closely followed the research. >I read every study on this subject. The recent >Healy and Martinez studies were rather >compelling. If there is a suicidal signal, it is >brief, early, and small. Medical management can >handle these issues.
Lar, dispite your independant research, you are not the final say. And you have not read every study on the subject. (oh I know I'm going to get banned)
>She's in the ballpark. She's the candy floss.
?
>They can induce psychosis, yes. They can trigger >mania, certainly.
Agreed.
>I was meaning her evidence. Her hypotheses are >not directly connected to evidence. I'm being >generous. Myrrh oil? All mental illness is sugar >related? (or something like that)From my school of thought, if somebody argues something, and another has evidence to support it, then it becomes his evidence.
>It's far from closed. And I am not trying to >shut the door. I'm trying to lay a solid >foundation of empirical evidence, and put to >rest hyperbole and fear-mongering.
Fear mongering wakes people up. Bad things can happen behind closed doors, and sometimes raising appropriate concern is a good thing. Where her arguments are not appropriate, I do not support them.
Linkadge
Posted by linkadge on December 15, 2005, at 19:13:43
In reply to Re: Tracy, Breggin, and other quacks... » linkadge, posted by Larry Hoover on December 15, 2005, at 0:34:45
>Do you have any idea of the doses used in that >study? Off the top of my head, I think it was >360 times the maximum human dose, maintained for >12 weeks (equivalent to 15 years of a human life >span). And I think the hypothalamic dendrites >were corkscrewed, not the receptors. I don't >recall for sure.
Fair enought, this study may not be applicable. This is not the only study.
>Who should have known better to simply >generalize to people taking the drug as >prescribed. There are toxic thresholds. Novel >effects that only occur at or above certain >concentrations. These are called toxicoses. >There is no reasonable extrapolation from that >mouse experiment to any human experience >conceivable.Like I said, there are other studies. It is necessary to look at each piece of evidence at a time. Are his coments about the dangers of neuroleptics untrue? Are his comments about the dangers of ECT all inacurate?
Wasn't it you who requested a "Do not ECT" affixed to medical information? What are you reasons for being against ECT? Who else will people listen to. "Good" doctors don't warn against its detremental effects.
>He's a quack because he cherry-picks quotations >from studies, reports secondary and tertiary >references as if they were primary, reports data >out of context, and ignores the published >conclusions of the study authors. He also has >been shown to fabricate the odd bit of data.This is the way I see it. Some psychiatrist think they can lie to you because it is in your best interest of mental health. Breggin is playing the other role. So he may lie from time to time. Perhaps he things the ends justifies the means. (or however the saying goes)
>If you've got the time, you can take Breggin >apart, too.
YOu may be able to pick at parts of their arugments but you can never dismatle the whole. That is why these individuals have lasted this long, because a portion of what they are saying is absolutely true.
Linkadge
Posted by linkadge on December 15, 2005, at 19:15:42
In reply to Re: What! » linkadge, posted by Larry Hoover on December 15, 2005, at 1:51:46
Correlation does not imply causation.
Suicide rates go up and down.
Linkadge
Posted by jamestheyonger on December 15, 2005, at 20:07:12
In reply to Re: Dr. Tracy on SSRIs.., posted by linkadge on December 15, 2005, at 19:01:44
>
> >There is no autopsy evidence for SSRI >potentiation of suicide. But alcohol? Huge. >Widely available, without a prescription.
>
> I don't think that autopsy information is
> necessary.
>Huh ? An autopsy defines the cause and contributing factors of death. It could not be more relevant.
Posted by Larry Hoover on December 15, 2005, at 23:07:13
In reply to Re: Dr. Tracy on SSRIs.., posted by linkadge on December 15, 2005, at 19:01:44
> >I read it. There was no evidence presented that >the pre-synaptic neuron would release identical >amounts of serotonin under both transporter >conditions, nor any evidence presented that COMT >or MAO-A concentrations were the same.
> But the point is that the level of the protein is reduced.
They measured one variable in a complex (i.e. multivariate) system.
> If our theory of depression is that the *5-ht* reuptake mechanism is too active in depression, then this is information to suggest against it.
But that's not a common theory. (I've never heard it before, myself.) Rather, the integrated serotonin signal in a pathway or pathways is believed (by some) to be weaker in depression. In order to strengthen the signal, without resorting to indiscriminate serotonin release, existing signals may be amplified by extending the half-life of serotonin in the synapse. The hope is to enhance the magnitude of pre- and post-synaptic receptor response, contributing to the integrated signal across that neural network. If I recall correctly, the increase in half-life is measured in fractional seconds. That's one theory. <shrug>
> Of course there could be compensatory changes in MAO-A, but this could also happen in patents treated with SSRI's.
That's one of *my* arguments, against your theory. You can't just measure reuptake transporter protein, and fail to simultaneously measure MAO-A concentration, COMT concentration, and total serotonin released into the synapse. And then do the same with an antidepressant present. And then do it again, two weeks later. And so on.
The whole idea that SSRIs function by flooding the brain with serotonin is patently absurd. Reuptake inhibition takes place immediately, whereas physiological antidepressant response takes weeks. It couldn't possibly be the explanation.
And, for the same reasons, global excess serotonin is equally absurd.
> >There is no evidence to reach that conclusion. >It is a conceivable hypothesis, but it has never >been tested.
> Scientists like to study one gene at a time. It makes sence to see if the 5-ht transporter is associated with depression or not. It's just like if you found low acetylcholinsterase in Alzeimer's disease, then it might make one rethink the model.
Scientists must also delay promoting their pet theories until such time as they have evidence to describe the relationship between multiple variables upon which their theories rest.
Did you see the recent work on SERT polymorphism? Out of 96 subjects, they found 27 variants, 21 of which were previously unknown. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15993855&query_hl=2
In such complex systems, I simply avoid mechanistic arguments altogether. I don't even pretend to have a clue.
> >The only easily tested hypothesis which arises >from this heterogeneity of SERT promoter regions >is to determine if SSRI response is different >under the three natural populations. It may well >explain why SSRIs don't work for everybody. Or >part of the why.> One researcher found that individuals with the long varients of the transporter responded better to SSRI's than did those with the short varients.
Babblemail me a good email address, and I'll send you the full-text of the above article.
> >SSRIs are depressogenic?
> Yes, I would argue that they can be for certain individuals. Mood may be maintained by a very delicate ballence between serotonin and dopamine. If you get too much serotonin, I think it can cause depression. I experienced a distinct worsening of all core symptoms of depression on paxil.
I meant generally. You can't project your experience without bias. It's a poor strategy because it fools you. Now, to say something can happen can be proven with but a single case. Amongst the (probably) billions of doses of SSRIs, I would argue that the most general conclusion is that SSRIs are not depressogenic.
You cannot apply that general conclusion to an individual. But that same argument cuts both ways. You cannot generalize from individual experience.
> >Suicide rates are falling.
> >http://www.afsp.org/statistics/USA.htm> But to associate this with SSRI use may not be accurate.
It's easy to use the word "may". What I would look for, though, is evidence for that anti-suicide agent that must be present for the initial thesis (SSRIs induce suicide) to be true. To argue that SSRIs induce suicide, while the evidence for a population shows an inverse relationship, requires that one demonstrate an independent variable of greater suicide reduction potential than the putative SSRI suicide inductive effect.
> >There is no autopsy evidence for SSRI >potentiation of suicide. But alcohol? Huge. >Widely available, without a prescription.
> I don't think that autopsy information is necessary.
Perhaps not necessary, but informative. It makes the SSRI-suicide link look a tad anemic. 40-45% of suicides positive for alcohol. Ever seen a suicide warning on a can of beer? Just a couple of examples...
Forensic Sci Int. 2005 Jan 17;147 Suppl:S25-8.
Fatal suicide cases from 1991 to 2000 in Szeged, Hungary.Havasi B, Magori K, Toth A, Kiss L.
Department of Forensic Medicine, University of Szeged, 6722 Szeged, Kossuth L. sgt. 40, Hungary. havasi@anat-fm.szote.u-szeged.hu
The aim of this study is to analyze the fatalities due to suicide in the period of 1991-2000. The autopsy reports of 719 suicide cases during that period of the Department of Forensic Medicine, University of Szeged were reviewed retrospectively. The victim's age, sex, way of commitment, place of death, the presence of alcohol and drug influence and survival time were recorded. Five hundred and one of the (69.6%) total 719 suicide fatalities were men and 218 (30.4%) were women. The largest age groups were 41-50 in men, in women we experienced a 'double-peak' of age groups 41-50 and 71-80. The most frequent way of committal was hanging (46%). The results revealed that 38.8% of the 474 victims whose blood and/or urine alcohol concentration measurement were carried out consumed alcohol prior to the act. The presence of licit drugs in 12% of not drug-related cases were experienced.
Forensic Sci Int. 1996 Apr 2;78(2):157-63.
Pathoanatomic findings and blood alcohol analysis at autopsy (BAC) in forensic diagnoses of undetermined suicide. A cross-cultural study.Ferrada-Noli M, Ormstad K, Asberg M.
Department of Clinical Neuroscience, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
In Sweden, ca. 25% of unnatural deaths ascribed to self-inflicted injury are finally recorded as 'undetermined suicide' (abbreviated UMSA), i.e. the forensic pathologist has not been able to establish whether the fatality was an accident or a suicide. In the present study, a series of UMSA cases was investigated with the aims to study the impact of immigrant status, and alcohol abuse on the occurrence of this forensic diagnosis on the mode of death. The alcohol issue was addressed by focusing on blood alcohol concentrations at autopsy (BAC) and post mortem signs of alcohol-related organ pathology. The results can be summarised as follows: Positive BAC occurred at an equal rate in the UMSA group and in definite suicides, i.e. about 45%. Among non-Swedish UMSA victims positive BAC was more common (50%) than among the Swedish (41%), whereas no difference was found in the definite suicide group. The level of BAC at autopsy was significantly higher in Finnish immigrants than in other ethnic groups. Organic signs of chronic alcohol abuse were found in 13 of 40 cases testing positive for BAC; thus, presence of alcohol at autopsy may reflect incidental intake rather than habitual overconsumption.
> >No, it doesn't. It links a homozygous gene to >those events. Not SSRIs.> I realize that. It is not a direct link, but it is something that has really baffled a lot of researchers. I emailed Dave on www.biopsychiatry.com and asked him what he thought about the issue of the serotonin transporter, and some of the recent findings. He said to me, that sometimes in psychiartry you will find things that don't fit the mold. Sometimes the findings will seem to indicate the exact opposite.
I don't know what you mean by your closing sentence. And, I was refuting any connection between the gene findings and SSRI effects. It is petitio principii, begging the question, to accept that the SERT promoter polymorphism tells us anything about SSRIs. It certainly isn't a conclusion obtainable from the evidence presented.
> SSRI's may *work* through a different mechanism alltogether. We have serotonin uptake inhibiting drugs that have no antidepressant potential whatsoever. All of the currently available SSRI's increase the activity of the gabaergic neurosteroid allopregnalone, some 20 fold.
I have absolutely no doubt that reuptake inhibition is possibly a tiny, and perhaps even inconsequential, aspect of their mechanism of effect. I'm sure we'll keep finding more and more effects, that we never anticipated finding.
> >Or Tianeptine might work on homozygous short->short SERTs?
> Well this is it. I was just more surprised by the fact that the study seemed to suggest that the most chronically depressed posessed the double short varient.
I think it's premature to make anything out of this finding. We don't know if the gene is pleiotropic, for example.
> >I strongly reiterate. There is no pathological excess serotonin state.> I strongly reiterate. Some researchers think that excessive serotonergic function in certain areas of the brain result in anxiety.
You're starting to come off the Tracy position. The key is *localization* of the serotinergic activity. And the activity in that locality is a relative finding.
> There are researchers who believe that certain generalized anxiety disorders are due to elevated serotonin activity. Some think high serotonergic neurotransmission may be involved in anorexia.
> http://www.mhsource.com/expert/exp1041502a.html
This example is nothing more than a poor explanation to a layperson.
The key point, I state for the umpteenth time, is localized serotinergic activity. There is no global excess serotonin state.
> >Getting back to how this phrase came into our >discussion, Tracy claims that this "excess >serotonin" state causes premature aging. You >seem to have just contradicted that, quite >explicitly.> I don't see what you mean.
You clipped it. You said:"If any drug were capable of mimicing some the catastrophic alterations in cognition an sentience that are evident in old age, I'd like to know about it."
If SSRIs cause this excess serotonin state, which causes premature aging (all her language), then your contention that there is no drug that could cause that certainly absolves SSRIs of any possibility of doing so, eh?
> There are theories out there as to how SSRI's may advance aging. The melatonin theory sounds convincing. I can see how chronically lowering melatonin might acellerate aging. There are other theories too.
Which is it, then? SSRIs to blame, or no drug can do it (mimic aging)?
The thing I keep having to point out, Ian, is that a theory is proof of nothing. Where are the data?
> >No, not potentiation. "...all data were >compatible with additivity of effects rather >than true potentiation."> The article says that fluoxetine substituted for LSD in certain paradigms.
You said potentiation. That is not potentiation. The dogs were preconditioned (read their normal receptor function was altered). It wasn't a naturalistic observation, this somewhat congruent drug effect.
> >The one above was about dogs. I wonder just what >the dogs said to describe their experiences.> This is about findings that may confirm some of the experiences that people have had.
I don't think it does anything of the sort.
I'll say it as often as I have to. That there are adverse events, serious adverse events, is not in question. With the billions of doses of these drugs consumed, it would be inconceivable for there not to be such events.
Do you have any idea what the death rate is from NSAIDs, each year? It exceeds the rate of suicide, from all causes, let alone from SSRIs. Context.
> >And, individual idiosyncratic reactions happen >all the time.
> It is not an idiosyncracy.
"An abnormal susceptibility to some drug, protein or other agent". Normal being all the rest.
> Both agents potently stimulate certain sertonin receptors.
Few people hallucinate on SSRIs. Using COSTART terminology, the reaction is uncommon to rare.
> We have no problem accepting that GI effects may be due to excess 5-ht3 stimulation, but yet cannot believe that people have had perceptual disturbances consistant with excess 5-ht2a agonism ?
I believe it happens. It's uncommon. When it does happen, the offending agent may be discontinued, and relief is then sought elsewhere.
> There are some documented cases of antidepressant induced perception disorder on www.biopsychiatry.com in addition to expert explainations of the events.
I am not arguing "never", Ian.
> >How? Who the heck knows that?
> Exactly. We can pop a pill based on unproven theory,
I have never popped a pill based on unproven theory. Not ever. I have, however, taken pills based on evidence for efficacy, notwithstanding the potential for idiosyncratic reactions.
> yet we start wars in defence of drugs based on unproven theory. She is not the only one who has attacked the theory behind SSRI medications.
I fail to follow the import of your argument. Empiricism is the basis of all pharmacological treatment. Theories of mechanism are to calm those who don't trust empiricism. Or something. We have discovered that they work. We have not discovered why.
> >That's what I meant earlier about mechanistic >arguments. They really are pointless.
> So what good is it to say that she is devoid of proof, when we have no proof of the opposite. Her proof may be our lack of proof.
Proof would be data. Empirical data. Not theory. You can throw words at something for days, and it will remain a mystery. Measure it, however, and you have data. She claims blood sugar relationships to mental illness. It should be blessedly easy to come up with supporting data. Same with her magic oils. Data?
> >Other people, with different beliefs, discovered >salicylic acid in willow bark, derived a >synthetic form, and made a near-bankrupt German >dye chemist named Bayer very rich.
> True, but we later learned how aspirin causes more deaths each year than any other drug (I believe). I am not going to try and dismiss the information that points to the dangers of aspirin.
But that's empiricism. That's my point, all along. Red willow spirit mechanism arguments won't stop someone from bleeding to death due to gastric perforation.
BTW, aspirin would never make it to market today, as a prescription drug. That it is an over-the-counter remedy is a quirk of history. It is still legal today to do trans-orbital frontal lobotomies, under the same sort of grandfathering legislation.
> >That's not hyperbole.> Did I say it was ?
Please be more careful with your editing. You might as well have left those bits out, considering the context was already taken away.
> >And we don't know why. But we do know that they >work. Empirical evidence.> It is a truth that the drug company can still market a drug when only 1/8 of the studies show any benefit.
Yes, it is a truth. Not because they have a theory. Because they have empirical evidence sufficient to convince the regulatory authorities that having the drug is better than not having it.
> >How about promoting better medical management. >More personal interaction with caregivers. >Providing critical information for true informed >consent. No fear-mongering required.
> Fair enough.
Good. Tracy, go away.
> >Post hoc ergo propter hoc is a fallacious >interpretation, a good part of the time.
> >You may have other medical concerns.> I'm sorry I brought it up. I didn't know you were going to be one of those people.
I'm offended.
A study with N=1 proves nothing. It *may* disprove some things. Your argument is affirmative, and therefore inherently indeterminate.
> >Sometimes, they do. And if appropriate >precautions had been taken, and corrective >action initiated at the first sign of trouble, I >think that many of the most serious outcomes >would simply never have happened.
> For certain individuals, the kind of monitoring necessary is not tangable. Monitoring cannot prevent all potential problems. Monitoring cannot prevent T.D. for instance, with neuroleptic use.
I did not say all. Monitoring can, in fact, minimize chronic TD in neuroleptic use, with prompt discontinuation.
> >I didn't listen to the whole interview.> I know
Biblical prophecy, remember? There is no science in that. Vague generalizations, anecdote, and biblical references attest to her quality of argument. Oh, and that gooey glossy stuff.
> >I have read through some of the complete >clinical trial data for some of the SSRIs.
..
> > If you want to see that, I'll dig it up and show >it to you.> You are one individual. Other individuals have analayed similar data, and have come to different conclusions.
Again, I resent the implication. I already presented expert verification of my prior work.
http://www.dr-bob.org/babble/20051211/msgs/588011.htmlThe data are the science. I verified the data. The faulty summaries are not the science.
> >All else is interpretation.
> Thats the problem. The argument in support of these drugs is interpretation.
The argument in support of these drugs is empirical. Raw statistical data for efficacy.
> The mechanisms are theoretical.
I'm glad you've picked up on that.
> When you don't know why they work, and why they fail, then interpretation becomes more tangable.
This sentence is confusing to me. We don't know why they work, and we don't know why they fail, and you can argue about it forever and be no closer to settling it. You need appropriate data. Data that have not yet been collected.
> >Link, I have very closely followed the research. >I read every study on this subject. The recent >Healy and Martinez studies were rather >compelling. If there is a suicidal signal, it is >brief, early, and small. Medical management can >handle these issues.
> Lar, dispite your independant research, you are not the final say.
I'm offended again. I am encouraging debate. I'm sorry if you struggle with the arguments I raise. The data in support of Tracy (and others) are absent. Theories have been bandied around as if they were fact.
> And you have not read every study on the subject. (oh I know I'm going to get banned)
My apologies, for failing to use the word 'recent', i.e. last six years, and some earlier stuff.
> >She's in the ballpark. She's the candy floss.
> ?
It was metaphorical.
> >I was meaning her evidence. Her hypotheses are >not directly connected to evidence. I'm being >generous. Myrrh oil? All mental illness is sugar >related? (or something like that)
> From my school of thought, if somebody argues something, and another has evidence to support it, then it becomes his evidence.
Fine. Please give empirical support for essential oils and blood sugar regulation in the successful treatment of mood disorders.
> >It's far from closed. And I am not trying to >shut the door. I'm trying to lay a solid >foundation of empirical evidence, and put to >rest hyperbole and fear-mongering.
> Fear mongering wakes people up. Bad things can happen behind closed doors, and sometimes raising appropriate concern is a good thing.
Appropriate concern raises its own attention.
> Where her arguments are not appropriate, I do not support them.
> Linkadge
Chacun a son gout.
Posted by Larry Hoover on December 16, 2005, at 9:22:47
In reply to Re: Tracy, Breggin, and other quacks..., posted by linkadge on December 15, 2005, at 19:13:43
> Like I said, there are other studies. It is necessary to look at each piece of evidence at a time. Are his coments about the dangers of neuroleptics untrue? Are his comments about the dangers of ECT all inacurate?
I don't know, but if you'd like me to predict, based on his work re: SSRIs, then I would say that he has likely used the same sorry tricks.
> Wasn't it you who requested a "Do not ECT" affixed to medical information? What are you reasons for being against ECT? Who else will people listen to. "Good" doctors don't warn against its detremental effects.
The decision was personal, and is quite the reason why informed and consent are part of the procedure before a major medical intervention. It matters not what other doctors thought, in the end. It matters what I thought. And my identity, such as it is, has formed alongside a fairly competent and powerful intellect. Any threat to that access, to recall, to partake of that identity was an unreasonable risk, for me. I would rather remain depressed than take that risk, even if later judged incompetent to make such a decision. My wishes were in writing, and enforceable. Just like a "do not resuscitate", I drew up a "do not ECT". My brain. My call.
> >If you've got the time, you can take Breggin >apart, too.
>
> YOu may be able to pick at parts of their arugments but you can never dismatle the whole.I disagree. Good science stands quite vividly, on its own. Bad science screams and dances and uses flashing lights. But when the people with the magnifying glasses show up, it just isn't there, at all. Bad science can be deconstructed using its own language. Its own logic. And its failure to show why other competing conclusions are not as reasonable, or are less reasonable, than is the bad science.
It can be a large to task to reverse the effect of well-publicized bad science. We're swamped with it. Like dietary cholesterol being a health risk. Or sodium being a heart unfriendly ion. In limited cases, these arguments hold, but for most people, health deteriorates on these guidelines.
I simply wish I had the health to do some deconstructing, and go public with the challenges that deconstruction uncovers. As I've said many times, I'm an empiricist. Show me the data. Show me how you collected them. Show me what you did to derive your stats/pattern/what have you. The science is the data. All else is human ego waving its hands to the curious or the frightened.
It is human nature to jump to conclusions. It is a scientist's job not to do so. On good data, any competent scientist will reach a fairly similar conclusion. But even competent scientists make mistakes. And I don't care if you won the Nobel prize, I'll start at your data, and your methodology, and take a look for myself.
And I play devil's advocate a lot. I don't express my own opinions, a good part of the time. That's because the deconstruction process itself reveals serious problems. I point out those problems, without even needing to reassess and come to conclusions of my own.
And, Ian, that's why I didn't listen to the whole taped interview of Dr. Tracy. I'll grant her that conceit, that honorific, one last time. When a building is constructed on weak foundations, gravity will bring it down. When a scientific theory is founded on weak (or nonexistent) data, it takes thinking people to bring it down. I challenge people to think. And I mean never to hurt feelings, though I know that I do. I'm not a perfect debater.
So, I apologize if I have crept into the personal. As I keep saying, good science stands for all to see. I needn't embellish any of that.
> That is why these individuals have lasted this long, because a portion of what they are saying is absolutely true.
>
>
> LinkadgeNo. These individuals have lasted this long because they give comfort to people who are hurt. But in the end, they do more harm than they have done good. Like the boy crying wolf. Or Chicken Little. They dishonour that core truth, by wrapping it in false clothes. And when the discrediting comes, the core truth may fall in the wasteheap, as well.
The reason I looked into the science of adverse effects of SSRIs arose from my own experience. I experienced psychotic dysphoric mania on an SSRI. My complaints fell on deaf ears. My repetitive cries that sleep grew harder to obtain, until I stopped sleeping altogether, were ignored. And then Serzone, nearly killed me in just 11 days.
But when I looked at the "science" presented by the Tracy/Breggin crew, there was a sheep in wolf's clothing. (note the inversion)
And no matter how much credit people want to give to the Tracys and Breggins, it was the Healys who did the job. They lobbied with real data, hard science, and the re-examination began.
My experience teaches me. I don't blame the drugs. I asked for them. And they were provided to me, in good faith.
I don't expect anyone to agree with my position. I do ask that it be considered. I join in the debate.
And the chips fall, hopefully, with nothing more revealed, at the end, than the science. The empirical evidence.
Have you heard the phrase, "the more you know, the less you know", or some variant? I think it's from the awareness of how much of what we collectively think we know is no more than a tissue of conjecture. It makes me want to be back in the lab, recording data. <sigh>
I didn't know I was going to ramble on, so. Realizing that I have, I now close.
Lar
Posted by Larry Hoover on December 16, 2005, at 9:41:26
In reply to Re: What!, posted by linkadge on December 15, 2005, at 19:15:42
> Correlation does not imply causation.
>
> Suicide rates go up and down.
>
> LinkadgeHmmm. It's hard to guess just what it was in my lengthier post that was the progenator of this brief response.
Tracy says SSRIs kill, via suicide. SSRI presciption rates have skyrocketed. This implies?
We look at available data, independently collected by reputable scientists for reputable motives, and we do not see the implied signal.
To the stats. Correlation is not evidence of causation. I would argue that it does imply it, based on my perception of human nature.
However, correlation has four categories of explanation.
1. Some variable A leads to some measurable change in variable B.
2. Some variable B leads to some measurable change in variable A.
3. It was a fluke. There is no relationship between A and B, but you measured a group unrepresantative of the greater population.
4. Some unmeasured variable C, leads to measurable change in both variable A and variable B.This is where the tough thinking begins. Hypotheses form. The thing is, the first 2 cases are indistinguishable. It doesn't matter how you graph them (which variable is the arbitrary independent variable, on axis X, and which is the dependent, graphed on Y), the very same coefficient of correlation will be obtained, with indentical significance.
What most people also fail to consider, even when numerous experiments have narrowed it down to e.g. A probably causes B, you can never exclude the fourth explanation.
Scientists do, however, love to assign probability to their data, i.e. the probability that their data is not a fluke observation.
It is my opinion that the probability that there has been a net suicide increase due to SSRI exposure is close to nil. Unfortunately, tragedies have occurred. And I will always be saddened by that realization. I think we have let people down. I pray we bring all our resources together to prevent all that we can. By looking at all available data, we now know when the vulnerable periods are.
Lar
Posted by Larry Hoover on December 16, 2005, at 9:46:44
In reply to Re: Dr. Tracy on SSRIs.., posted by jamestheyonger on December 15, 2005, at 20:07:12
>
> >
> > >There is no autopsy evidence for SSRI >potentiation of suicide. But alcohol? Huge. >Widely available, without a prescription.
> >
> > I don't think that autopsy information is
> > necessary.
> >
>
> Huh ? An autopsy defines the cause and contributing factors of death. It could not be more relevant.There was a study done in Utah, which has the dubious distinction of having the highest prescription rate for SSRI antidepressants. The blood from 49 adolescent suicide victims was analyzed. Not one of the subjects had detectable SSRI in their blood. However, 24% of the youths were prescribed these drugs. What is the perception (without knowledge found at autopsy)? And how does it differ from fact?
Funny. Although she is from Utah (or bases her offices there, or something), I have never heard her mention this information.
Lar
Posted by linkadge on December 16, 2005, at 10:12:42
In reply to Re: Dr. Tracy on SSRIs.., posted by jamestheyonger on December 15, 2005, at 20:07:12
But I am wondering what you mean by autopsy indicating SSRI potentiation of suicide? Is it routeen for a person who has killed themseves with a gun to be tested for levels of antidepressants in their system ? I am just questioning what kind of data may be collected, and I don't see how an autopsy would disclude a link between SSRI's and suicide since the death may not be an overdose of SSRI's.
Linkadge
Posted by Larry Hoover on December 16, 2005, at 11:16:06
In reply to Re: Dr. Tracy on SSRIs.., posted by linkadge on December 16, 2005, at 10:12:42
> But I am wondering what you mean by autopsy indicating SSRI potentiation of suicide?
I'll rephrase. We can compare population exposure to a substance, and autopsy evidence for exposure to a substance, and see if the incidences differ.
The idea that SSRI exposure somehow leads to suicide is testable.
Tracy suggested that was the case. If SSRIs potentiate suicidal thinking and acts, we'd observe disproportionation at autopsy.
> Is it routeen for a person who has killed themseves with a gun to be tested for levels of antidepressants in their system ?
Absolutely not. (Except in parts of Scandinavia. They document everything.) But the question was asked. And some medical examiners have looked. They recorded the data, and gave summary statistics. The pattern in those statistics is inconsistent with an SSRI-triggering theory.
> I am just questioning what kind of data may be collected, and I don't see how an autopsy would disclude a link between SSRI's and suicide since the death may not be an overdose of SSRI's.
>
> LinkadgeOverdose of SSRIs seldom leads to death. So seldom, that it is reported in case report form in medical journals. But the very presence or absence of SSRI drugs in known suicide may reveal important relationship-type data.
We look to toxicological data, such as exposure to e.g. cocaine, alcohol, amphetamines, neuroleptics, antidepressants, marijuana, and so on, in a series of confirmed suicides. Method of suicide is not considered. The blood evidence for exposure to drugs, etc. is simply listed. Then, we can compare this suicide population, to the general population, based on known exposure patterns. And, what we find is an under-representation of proven SSRI exposure in known suicides. Alcohol exposure runs at about 40%, give or take, in known suicides. Just as a contextual element, I raise alcohol exposure.
Here's a sample of the SSRI data.
Acta Psychiatr Scand. 2005 Apr;111(4):286-90.
Comment in:
Evid Based Ment Health. 2005 Nov;8(4):113.
Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides.Isacsson G, Holmgren P, Ahlner J.
Neurotec, Division of Psychiatry, Karolinska Institute, Stockholm, Sweden. goran.isacsson@neurotec.ki.se
OBJECTIVE: To test the hypothesis that selective serotonin reuptake inhibitor (SSRI) antidepressants may have a suicide emergent effect, particularly in children and adolescents. METHOD: Detections of different antidepressants in the forensic toxicological screening of 14 857 suicides were compared with those in 26,422 cases of deaths by accident or natural causes in Sweden 1992-2000. RESULTS: There were 3411 detections of antidepressants in the suicides and 1538 in the controls. SSRIs had lower odds ratios than the other antidepressants. In the 52 suicides under 15 years, no SSRIs were detected. In 15-19-year age group, SSRIs had lower relative risk in suicides compared with non-SSRIs. CONCLUSION: The hypothesis that treatment of depressed individuals with SSRIs leads to an increased risk of suicide was not supported by this analysis of the total suicidal outcome of the nationwide use of SSRIs in Sweden over a period of 9 years, either in adults or in children or adolescents.
Br J Psychiatry. 1999 Mar;174:259-65.Comment in:
Br J Psychiatry. 1999 Jul;175:90-1.Psychotropics and suicide prevention. Implications from toxicological screening of 5281 suicides in Sweden 1992-1994.
Isacsson G, Holmgren P, Druid H, Bergman U.
Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Sweden. Goran.Isacsson@cnsf.ki.se
BACKGROUND: Systematic clinical investigations of consecutive suicides have found psychiatric disorders in 90-95% of subjects (depressive disorder 30-87%). AIMS: To investigate use of psychotropics in men and women of different ages who commit suicide. METHOD: Results of toxicological screening in 5281 suicides in Sweden 1992-94 were studied. RESULTS: Psychotropics were detected in 45.3% of the suicides. Antidepressants were detected in 12.4% of the men and 26.2% of the women (7.2% and 14.2%, respectively, of those under 30 years of age). Neuroleptics or antiepileptics (in the absence of antidepressants) were detected in 8.3%, and anxiolytics/hypnotics alone in 20.5% of the subjects. Overdose by an antidepressant was the probable cause of death in 2.1% of the men and 7.9% of the women. CONCLUSIONS: The pattern of psychotropics detected in toxicology was incongruent with the pattern of diagnoses found in the clinical investigations of suicides mentioned above. Depression appears to be under treated in individuals committing suicide, especially in men and in subjects under 30 years of age.
Just for its thought-provoking capacity, I present the following. There is a powerful correlation between homicidal violence and vegetable oil consumption (dominant source of omega-6 fatty acids). Just look at that correlation coefficient (r = 0.94) and the significance (P < 0.00001). That's less than 1/1000th of 1% chance the observation is a fluke, with 88% of the variation (r squared) attibutable to this variable.Makes me wonder much more about diet than drugs.
Lar
Lipids. 2004 Dec;39(12):1207-13.Increasing homicide rates and linoleic acid consumption among five Western countries, 1961-2000.
Hibbeln JR, Nieminen LR, Lands WE.
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA. jhibbeln@mail.nih.gov
Clinical intervention trials and animal studies indicate that increasing dietary intakes of long chain n-3 FA or reducing linoleic acid intake may reduce aggressive and violent behaviors. Here we examine if economic measures of greater n-6 consumption across time and countries correlate with greater risk of homicide. Linoleic acid available for human consumption was calculated from World Health Organization disappearance data for 12 major seed oils in the food supply for the years 1961 to 2000 in Argentina, Australia, Canada, the United Kingdom, and the United States (US). Homicide mortality rates, adjusted for age, were obtained from the central judicial authority of each country. Apparent linoleic acid intake from seed oil sources ranged from 0.29 en% (percentage of daily food energy) (Australia 1962) to 8.3 en% (US 1990s). Greater apparent consumption of linoleic acid correlated with higher rates of homicide mortality over a 20-fold range (0.51-10.2/100,000) across countries and time in an exponential growth regression model (r = 0.94, F = 567, P < 0.00001). Within each country, correlations between greater linoleic acid disappearance and homicide mortality over time were significant in linear regression models. Randomized controlled trials are needed to determine if reducing high intakes of linoleic acid by seed oils with alternative compositions can reduce the risk of violent behaviors. These dietary interventions merit exploration as relatively cost-effective measures for reducing the pandemic of violence in Western societies, just as dietary interventions are reducing cardiovascular mortality. Low linoleate diets may prevent behavioral maladies that correctional institutions, social service programs, and mental health providers intend to treat.
Posted by linkadge on December 16, 2005, at 13:12:47
In reply to Re: Dr. Tracy on SSRIs.. » linkadge, posted by Larry Hoover on December 15, 2005, at 23:07:13
>They measured one variable in a complex (i.e. >multivariate) system.
Yes, but the drugs we are using are lauded for their specificity towards inhibiting that transporter.
>But that's not a common theory. (I've never >heard it before, myself.) Rather, the integrated >serotonin signal in a pathway or pathways is >believed (by some) to be weaker in depression. >In order to strengthen the signal, without >resorting to indiscriminate serotonin release, >existing signals may be amplified by extending >the half-life of serotonin in the synapse. The >hope is to enhance the magnitude of pre- and >post-synaptic receptor response, contributing to >the integrated signal across that neural >network. If I recall correctly, the increase in >half-life is measured in fractional seconds. >That's one theory. <shrug>
The reason that these intial stuides were done, was to try and find a link between the activity of SERT and depression. I am guessing that researchers hoped to find the opposite.
Researchers like to test certain suspect genes at a time. The study shows an association. Of course it does not *imply* that low activity of SERT causes depression, but it reveals an association.
What is surprising researchers is the direction of the association. If the low serotonin theory is true, and you have low activity of sert in depression, than you would require a even more significantly high activity of MAO-A, in order to maintain overall low serotonin. I supose that these individuals with low SERT may have extrordinarily high MAO-A. But it still goes to show that we may be attacking the system from the wrong angle. I mean if you want to make these individuals brain chemistry resemble that of a normal individual, does it make sence to push SERT activity down even further below the already low levels with an SSRI ?
>The whole idea that SSRIs function by flooding >the brain with serotonin is patently absurd. >Reuptake inhibition takes place immediately, >whereas physiological antidepressant response >takes weeks. It couldn't possibly be the >explanation.
Perhaps they may cause compensentory changes with the 5-ht system. Downregulation of 5-ht2 receptors? That can be done with 5-ht2a antagonists, surprisingly. It can also be done with melatonin, which acts functionally as a 5-ht2a antagonist. It may just be a consequence of normalized HPA axis function. Surmontil produces the same adaptive changes in receptor systems as other tricyclic antidepressnats, yet has no effect on monoamine uptake. So I argue, if serotonin uptake is unneccesary, might tampering with it cause problems ?
>Did you see the recent work on SERT >polymorphism? Out of 96 subjects, they found 27 >variants, 21 of which were previously unknown. >http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?>cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15>993855&query_hl=2Another argument against the widespread use of agents that affect the system in only one way.
>I meant generally. You can't project your >experience without bias. It's a poor strategy >because it fools you. Now, to say something can >happen can be proven with but a single case. >Amongst the (probably) billions of doses of >SSRIs, I would argue that the most general >conclusion is that SSRIs are not depressogenic.
Like I said, it depends on who you talk to. This board is full of acounts of antidepressants making certain peoples depression worse. Another argument I have is that they may worsen the course long term. For many, they cause insomnia for the duration of treatment. This may lead to more depressive symptoms long term.
>You cannot apply that general conclusion to an >individual. But that same argument cuts both >ways. You cannot generalize from individual >experience.
I realize that. But we know that antidepressants only work for a fraction of patients. There are many reports of antidepressant drugs worsening depression.
>It's easy to use the word "may". What I would >look for, though, is evidence for that anti->suicide agent that must be present for the >initial thesis (SSRIs induce suicide) to be >true.
Well thats it, the best you can argue is that SSRI's *may* reduce suicide.
>I don't know what you mean by your closing >sentence. And, I was refuting any connection >between the gene findings and SSRI effects. It >is petitio principii, begging the question, to >accept that the SERT promoter polymorphism tells >us anything about SSRIs. It certainly isn't a >conclusion obtainable from the evidence >presented.
It wasn't my closing sentence. Basically, I was under the impression that Dave was agreeing with me that some of the findings are baffling in terms of our current theories about what may be wrong.
>I think it's premature to make anything out of >this finding. We don't know if the gene is >pleiotropic, for example.
I think it is a great place to start. It indicates to use that the system is much more complex than the drug commercials make it out to be. It forces researchers to continue to reevaluate the theories. But most importantly, it leaves the door "open" to explainations as to why things can go awry with the drugs' use.
>You're starting to come off the Tracy position. >The key is *localization* of the serotinergic >activity. And the activity in that locality is a >relative finding.I see your argument has reformed too. The thing is this. SSRI's do not discriminate. They affect serotonin in the good parts of the brain, and the bad parts of the brain. If we have evidence to suggest that high serotonin activity in certain parts of the brain may lead to anxiety, then we have a start to understanding why SSRI's can make many peoples anxiety much worse. Tracy's argument is perhaps an overgeneralization. But it is a not completely inacurate. And no more simplistic than the drug comercial's proposed statements "anxiety is related to low serotonin".
>This example is nothing more than a poor >explanation to a layperson.
The drug companies try to fit things into a box too. They try to convince the public that it is all due to low serotonin, and that zoloft will fix it. Even if Tracy's arguments serve to stir the pot, and get people to look further into the issue, then I see it as a good thing. When she says that anxiety may be related to elevated serotonin, then this is not a lie. *Of course* we are reffering to a portion of the brain, but then so are *all* comments made about low serotonin being implicated in these states.
>There is no global excess serotonin state.
Ok, fine. That word "global" gets you away with a lot. But her arguments are with respect to the propensity of SSRI's to create some of the problems for which they are marketed to solve. Under that premise, information relating high serotonin in certain brain regions to say, anxiety, fear etc, become very relavant.
>If SSRIs cause this excess serotonin state, >which causes premature aging (all her language), >then your contention that there is no drug that >could cause that certainly absolves SSRIs of any >possibility of doing so, eh?
Your misunderstaning. I am referring to the fact that she brough the issue up. I am speaking about the relavance of the topic as if I was an uninformed listener. If the drugs cause (/the notion that the drugs cause) premature aging, is of importance to the patient.
>Which is it, then? SSRIs to blame, or no drug >can do it (mimic aging)?I think you are trying to define premature agining so stringently that the drugs could never fit the definition. Of course premature aging can not be completely defined, because we don't even know what causes agining. But in the sence long term use may create prematurely a number of symptoms associated with aging, it is not an unfathomable concept.
>The thing I keep having to point out, Ian, is >that a theory is proof of nothing. Where are the >data?
You are right. We are devoid of many long term studies on the safety of SSRI's. That is a big problem. Just like we don't really have many studies on the issue of "antidepressant poop out". I am sure you are able to accept the presence of antidepressant poop out, for instance, without a randomized double-blind, placebo controlled study indicating it occurs. If somebody got on the radio and said antidepressants poop out occurs, I wouldn't scoff the notion based on the absence of stringent trials. It is important to use our eyes and ears too.
>You said potentiation. That is not potentiation. >The dogs were preconditioned (read their normal >receptor function was altered). It wasn't a >naturalistic observation, this somewhat >congruent drug effect.
Potentiation. When the drug, fluoxetine, is capable of enhancing some of the effects that are characteristic of hallucinogens.
>I don't think it does anything of the sort.
Like I said, I am making an educated deduction. I am looking for more information on that topic.
>Few people hallucinate on SSRIs. Using COSTART >terminology, the reaction is uncommon to rare.I'm not so sure that all the side effects of this drug are adequately collected or reported. A lot of clicial trial information reports that sexual dysfunction happens in <14% of people treated with say lexapro. I'd be inclined to think that it happens in more than half. Let me guess. Where's my data?
>I believe it happens. It's uncommon. When it >does happen, the offending agent may be >discontinued, and relief is then sought >elsewhere.
Fortunately you never had to take these drugs while your brain and body was still developing. It is a time when you don't really know what is normal and what is not. As a teenager given SSRI's, it was very difficult to decide what was supposed to be normal. The severe GI disturbance I had, I thought was just related to psychosocial stress.
>I am not arguing "never", Ian.
For good reasons, please use my member name, thank you very much.
>I have never popped a pill based on unproven >theory. Not ever. I have, however, taken pills >based on evidence for efficacy, notwithstanding >the potential for idiosyncratic reactions.
Evidence for efficacy does not equate to proven theory, and a theory that has not been proven, is unproven.
>We have discovered that they work. We have not >discovered why.
We have discovered that they work sometimes. We have discovered that oftentimes they perform worse than placebo. We have discovered that often times we need 8 trials to show the drug performs better than the placebo. Those are truths.
>Proof would be data. Empirical data. Not theory.Exactly. Her radio broadcast attack the data supporting the use of the drugs. Like Healey believed, we do not have the whole story because we do not have all the data. When you are dealing with ratio type data, it is unfortunately necessary to have *all* of it.
>Please be more careful with your editing. You >might as well have left those bits out, >considering the context was already taken away.
You are reading into things.
>Yes, it is a truth. Not because they have a >theory. Because they have empirical evidence >sufficient to convince the regulatory >authorities that having the drug is better than >not having it.They have the evidence that in 1 out of 8 cases, having the drug is better than not having it.
>Good. Tracy, go away.
It is necessary to listen to the whole broadcast before dismissing it. Now you can't clearly see "what baby" if you havn't done that.
>I'm offended.
I am sorry. Did I, for one minaute, try to dismiss your manic reaction to Luvox; to say that it was not due to Luvox at all? Perhaps you had "other" things going on.
>A study with N=1 proves nothing.
Similarly, your manic reaction to Luvox proves nothing. (Now you no I don't believe that)
>Monitoring can, in fact, minimize chronic TD in >neuroleptic use, with prompt discontinuation.
Sometimes it does, sometimes it doesn't. Sometimes TD symptoms can be masked. But the fact is that the drug class can be linked to brain dammage.
>Biblical prophecy, remember? There is no science >in that. Vague generalizations, anecdote, and >biblical references attest to her quality of >argument. Oh, and that gooey glossy stuff.
Like I said before. I don't agree with everything she says, just the pieces of information she brings up that have truth to them. Like for instance the fact that a drug company can repeatedly test a drug without ever having to disclose the failing results.
>The data are the science. I verified the data. >The faulty summaries are not the science.
I can't see how you call those who reach other conclusions faulty. You saw, for instance a correlation between SSRI use, and the marginal reduction in suicide rates over the past few years. Others look to see that suicide rates have been this low before in the past 50 years and that the minimal decrease may be related to something else. There are different ways to interprate see the same data.
>The argument in support of these drugs is >empirical. Raw statistical data for efficacy.
I again bring up Healy's arguments against the merrit we have on the efficacy of these drugs.
I would not believe clinical trial data, unless I had access to the data of failed studies.>I'm glad you've picked up on that.
I'm glad too
>This sentence is confusing to me. We don't know >why they work, and we don't know why they fail, >and you can argue about it forever and be no >closer to settling it. You need appropriate >data. Data that have not yet been collected.
Exactly. Data that have not yet been collected.
>I'm offended again. I am encouraging debate. I'm >sorry if you struggle with the arguments I >raise. The data in support of Tracy (and others) >are absent. Theories have been bandied around as >if they were fact.
I am sorry. Just doing a simple Google search on the topic it is easy to see that there many different oppinions, and many different stances.
I am sorry you are resorting to binary tactics again. Struggle? When? Where?Different people, different conclusions. The Brittish decided to impose their prescribing restrictions not just based on the possability of increased suicide risk, but also based on what they saw as a general lack of proven efficacy of the drugs in this age group.
>My apologies, for failing to use the >word 'recent', i.e. last six years, and some >earlier stuff.
Even that is a meaningless statement, because it depends on what you deem to be "the topic". And yes there are studies that you have not read, namely the ones that the drug companies are under no obligation to publish.
>Fine. Please give empirical support for >essential oils and blood sugar regulation in the >successful treatment of mood disorders.
There is lots of information, and are many studies on the relationship between essentially fatty acids and mood disorders. That is a whole different topic.
Linakdge
Posted by Larry Hoover on December 16, 2005, at 15:28:13
In reply to Re: Dr. Tracy on SSRIs.., posted by linkadge on December 16, 2005, at 13:12:47
I really want to simplify. I'm exhausted from shovelling snow with one arm.
> >The whole idea that SSRIs function by flooding >the brain with serotonin is patently absurd. >Reuptake inhibition takes place immediately, >whereas physiological antidepressant response >takes weeks. It couldn't possibly be the >explanation.
> Perhaps they may cause compensentory changes with the 5-ht system. Downregulation of 5-ht2 receptors? That can be done with 5-ht2a antagonists, surprisingly. It can also be done with melatonin, which acts functionally as a 5-ht2a antagonist. It may just be a consequence of normalized HPA axis function. Surmontil produces the same adaptive changes in receptor systems as other tricyclic antidepressnats, yet has no effect on monoamine uptake. So I argue, if serotonin uptake is unneccesary, might tampering with it cause problems ?
Drugs that cause immediate increases in synaptic serotonin concentration, e.g. Ecstacy or powerful agonists e.g. LSD, stand in somewhat stark contrast from the serotonergic antidepressants, which take weeks for most of the effects to appear. (There are exceptions, but I'm just wanting to make a simple point.) So, serotonin receptor mediated events that lead to changes in regulatory behaviour in the neuron are most likely what makes an antidepressant an antidepressant.
I once posted an overview of changes in RNA concentration following antidepressant exposure. There were many dozens of significant changes, up to 20-fold. Just looking at permutation, we're already being forced to consider something like 10^17 possible meaningful interactions of those changes. I wish I could think of what the paper was called.
That's why I go back to empirics. We put this drug into a mysterious processor, and we observe these common outputs. How, why, why not.....I'll never pretend to know.
> >Did you see the recent work on SERT >polymorphism? Out of 96 subjects, they found 27 >variants, 21 of which were previously unknown. >http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?>cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15>993855&query_hl=2> Another argument against the widespread use of agents that affect the system in only one way.
But they don't affect the system one way. http://kidb.cwru.edu/pdsp.php
> >I think it's premature to make anything out of >this finding. We don't know if the gene is >pleiotropic, for example.> I think it is a great place to start. It indicates to use that the system is much more complex than the drug commercials make it out to be.
Commercials. They ought to make them stop direct marketing drugs.
But, Tracy falls in the same level of scientific truth. That's the problem with her.
> >The thing I keep having to point out, Ian, is >that a theory is proof of nothing. Where are the >data?> You are right. We are devoid of many long term studies on the safety of SSRI's. That is a big problem. Just like we don't really have many studies on the issue of "antidepressant poop out". I am sure you are able to accept the presence of antidepressant poop out, for instance, without a randomized double-blind, placebo controlled study indicating it occurs. If somebody got on the radio and said antidepressants poop out occurs, I wouldn't scoff the notion based on the absence of stringent trials. It is important to use our eyes and ears too.
Saying what happens is one thing. That is data collection, and description. That's empiricism. Of course poop out occurs, but if anyone tries to explain why, that's over the line.
> I'm not so sure that all the side effects of this drug are adequately collected or reported. A lot of clicial trial information reports that sexual dysfunction happens in <14% of people treated with say lexapro. I'd be inclined to think that it happens in more than half. Let me guess. Where's my data?No, those data are available. Post-marketing surveillance puts the rate at about 3 times that, off the top of my head. Clinical trials of efficacy are not designed to collect information that might be personal or embarassing. I may not mention my erectile dysfunction, but I'd surely mention hallucinations.
Here's the study I was thinking of:
J Clin Psychiatry. 2001;62 Suppl 3:10-21.
Comment in:
J Clin Psychiatry. 2002 Feb;63(2):168.Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction.
Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F.
University Hospital of Salamanca, Psychiatric Teaching Area, University of Salamanca, School of Medicine, Spain. angelluis.montejo@globalmed.es
BACKGROUND: Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and clomipramine, are frequently associated with sexual dysfunction. Other antidepressants (nefazodone, mirtazapine, bupropion, amineptine, and moclobemide) with different mechanisms of action seem to have fewer sexual side effects. The incidence of sexual dysfunction is underestimated, and the use of a specific questionnaire is needed. METHOD: The authors analyzed the incidence of antidepressant-related sexual dysfunction in a multicenter, prospective, open-label study carried out by the Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. The group collected data from April 1995 to February 2000 on patients with previously normal sexual function who were being treated with antidepressants alone or antidepressants plus benzodiazepines. One thousand twenty-two outpatients (610 women, 412 men; mean age = 39.8 +/- 11.3 years) were interviewed using the Psychotropic-Related Sexual Dysfunction Questionnaire, which includes questions about libido, orgasm, ejaculation, erectile function, and general sexual satisfaction. RESULTS: The overall incidence of sexual dysfunction was 59.1% (604/1022) when all antidepressants were considered as a whole. There were relevant differences when the incidence of any type of sexual dysfunction was compared among different drugs: fluoxetine, 57.7% (161/279); sertraline, 62.9% (100/159); fluvoxamine, 62.3% (48/77); paroxetine, 70.7% (147/208); citalopram, 72.7% (48/66); venlafaxine, 67.3% (37/55); mirtazapine, 24.4% (12/49); nefazodone, 8% (4/50); amineptine, 6.9% (2/29); and moclobemide, 3.9% (1/26). Men had a higher frequency of sexual dysfunction (62.4%) than women (56.9%), although women had higher severity. About 40% of patients showed low tolerance of their sexual dysfunction. CONCLUSION: The incidence of sexual dysfunction with SSRIs and venlafaxine is high, ranging from 58% to 73%, as compared with serotonin-2 (5-HT2) blockers (nefazodone and mirtazapine), moclobemide, and amineptine.
> >I have never popped a pill based on unproven >theory. Not ever. I have, however, taken pills >based on evidence for efficacy, notwithstanding >the potential for idiosyncratic reactions.> Evidence for efficacy does not equate to proven theory, and a theory that has not been proven, is unproven.
Ya, I think.
> >We have discovered that they work. We have not >discovered why.
> We have discovered that they work sometimes. We have discovered that oftentimes they perform worse than placebo. We have discovered that often times we need 8 trials to show the drug performs better than the placebo. Those are truths.
Maybe. Placebo response is the bugbear of mood disorder treatment. Placebo response in e.g. positive symptom schizophrenia is estimated at < 3%. Here is an excellent article about the difficulties in interpretation that arise because of the clinical trial system for medication being inappropiate for mood disorder treatments.
http://www.psychiatrictimes.com/p000429.html
> >I'm offended.> I am sorry. Did I, for one minaute, try to dismiss your manic reaction to Luvox; to say that it was not due to Luvox at all? Perhaps you had "other" things going on.
Exactly. Perhaps I did. It certainly took place. The role of Luvox is not clearly defined.
> >A study with N=1 proves nothing.> Similarly, your manic reaction to Luvox proves nothing. (Now you no I don't believe that)
You've confused me again, with your parenthetical remark. Nothing was proven, but it would be prudent for me to avoid that drug, in future.
> I again bring up Healy's arguments against the merrit we have on the efficacy of these drugs.That's why they did these studies. Healy's an author on the first one.
A meta-analysis of 702 clinical trials....
http://bmj.bmjjournals.com/cgi/content/full/330/7488/396And, another, of 477 more....
http://bmj.bmjjournals.com/cgi/content/full/330/7488/385And, a huge real-life observational study...
http://bmj.bmjjournals.com/cgi/content/full/330/7488/389
Posted by linkadge on December 16, 2005, at 19:08:13
In reply to Re: Dr. Tracy on SSRIs.. » linkadge, posted by Larry Hoover on December 16, 2005, at 11:16:06
>Absolutely not. (Except in parts of Scandinavia. >They document everything.) But the question was >asked. And some medical examiners have looked. >They recorded the data, and gave summary >statistics. The pattern in those statistics is >inconsistent with an SSRI-triggering theory.
In your words, n is an important factor. If this idea has not been tested widescale, then its not much good to us yet. Of course it is testable, but when larger studies come in I may be more convinved.
>Overdose of SSRIs seldom leads to death. So >seldom, that it is reported in case report form >in medical journals. But the very presence or >absence of SSRI drugs in known suicide may >reveal important relationship-type data.
But if levels of antidepressants are not a routeen check, then an association has not been proven conclusvely. Small studies showing a lack of association don't mean a whole lot.
>And, what we find is an under-representation of >proven SSRI exposure in known suicides. Alcohol >exposure runs at about 40%, give or take, in >known suicides. Just as a contextual element, I >raise alcohol exposure.
I am not arguing that isn't a testabe hypothesis. I am aruging that it hasn't been tested sufficantly.
>OBJECTIVE: To test the hypothesis that selective >serotonin reuptake inhibitor (SSRI) >antidepressants may have a suicide...This type of study is great, although this type of research is preliminary. The study came at a convenient time. I would need to see more studies of this type to conlcude anything. It also doesn't adress the fact that the drugs may indeed induce suicidality without resulting in suicide. People under medical care, also may be less likely to actually complete the act. It is fully possable that the drugs create the desire to die without triggering the act.
>Psychotropics and suicide prevention. >Implications from toxicological screening of >5281 suicides in Sweden 1992-1994.
There is another problem with these studies. They are testing levels of antidepressants within the blood of suicide victoms. This type of study is not geared to reveal any great association because you have a large group of untreated people pooled in which may downplay an association. There needs to be a double blind trial comparing suicidal tendancies induced by placebo vs. active SSRI.
>Increasing homicide rates and linoleic acid >consumption among five Western countries, 1961->2000.Thats great. This points to the idea that dietary deficiancy or functional deficiancy of n-3 polyunsaturated fats may lead to increased suicide. I don't know, does Tracy recommend elminating omega 3 in favor of O-6 ?
Linkadge
Posted by linkadge on December 16, 2005, at 20:06:15
In reply to Re: Dr. Tracy on SSRIs.. » linkadge, posted by Larry Hoover on December 16, 2005, at 15:28:13
>I really want to simplify. I'm exhausted from >shovelling snow with one arm.
Nobody is preventing you from taking a break.
>Drugs that cause immediate increases in synaptic >serotonin concentration, e.g. Ecstacy or >powerful agonists e.g. LSD, stand in somewhat >stark contrast from the serotonergic >antidepressants, which take weeks for most of >the effects to appear. (There are exceptions, >but I'm just wanting to make a simple point.) >So, serotonin receptor mediated events that lead >to changes in regulatory behaviour in the neuron >are most likely what makes an antidepressant an >antidepressant.
You are mixing two aguments. I am familliar with the proposed mechanisms of SSRI's, and I still contend that the observed cases of SSRI related visual disturbances are related to a LSD like serotonin agonism. SSRI's can act as potent agonists at all serotonin receptors.
>I once posted an overview of changes in RNA >concentration following antidepressant exposure. >There were many dozens of significant changes, >up to 20-fold. Just looking at permutation, >we're already being forced to consider something >like 10^17 possible meaningful interactions of >those changes. I wish I could think of what the >paper was called.
I don't see where you are going.
>That's why I go back to empirics. We put this >drug into a mysterious processor, and we observe >these common outputs. How, why, why not.....I'll >never pretend to know.
>But they don't affect the system one way.
They affect the serotonin transporter in one way.
>Commercials. They ought to make them stop direct >marketing drugs.
Agreed
>But, Tracy falls in the same level of scientific >truth. That's the problem with her.That statement needs to be applied to her various arguments separately.
>Saying what happens is one thing. That is data >collection, and description. That's empiricism. >Of course poop out occurs, but if anyone tries >to explain why, that's over the line.
You are waiting for empiracal proof that a drug may have faults, you may have waited too long.
>No, those data are available. Post-marketing >surveillance puts the rate at about 3 times >that, off the top of my head. Clinical trials of >efficacy are not designed to collect information >that might be personal or embarassing. I may not >mention my erectile dysfunction, but I'd surely >mention hallucinations.The point is that the data can oftentimes be inacurate.
>Maybe. Placebo response is the bugbear of mood >disorder treatment. Placebo response in e.g. >positive symptom schizophrenia is estimated at < >3%. Here is an excellent article about the >difficulties in interpretation that arise >because of the clinical trial system for >medication being inappropiate for mood disorder >treatments.
When you have a drug that is oftentimes performing no better than placebo, you'd better make sure it is safe. Thats what sparks this contoversy, the combination of questionable efficacy, and questionable safety.
>Exactly. Perhaps I did. It certainly took place. >The role of Luvox is not clearly defined.I believe you know yourself well enough to distinguish. For me it is simple, sinusoidal head movements, head twisting sensations, severe ballance problems, and a whole host of co-ordination problems usually resolve within 4 hours of taking zoloft or celexa.
>You've confused me again, with your >parenthetical remark. Nothing was proven, but it >would be prudent for me to avoid that drug, in >future.I would argue that it is information that could proove to be more usefull than for you simply avoiding the drug again. If you were my mother, you would probably have been subsequently persuaded that you have bipolar disorder, and have to suffer a life of lithium carbonate treatment. I don't think you have bipolar disorder, do you ?
That's why they did these studies. Healy's an author on the first one.>A meta-analysis of 702 clinical trials....
>http://bmj.bmjjournals.com/cgi/content/full/330/7>488/396"Discussion Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials."
>And, another, of 477 more....
>http://bmj.bmjjournals.com/cgi/content/full/330/7>488/385"Increased risks of suicide and self harm caused by SSRIs cannot be ruled out"
Thanks, that saves me the trouble.
Linkadge
Posted by Larry Hoover on December 16, 2005, at 20:34:41
In reply to Re: Dr. Tracy on SSRIs.., posted by linkadge on December 16, 2005, at 19:08:13
> I am not arguing that isn't a testabe hypothesis. I am aruging that it hasn't been tested sufficantly.
Those weren't small studies, and the null hypothesis was accepted. The alternate was rejected. Not by opinion, but by hypothesis testing (statistical analysis).
> >OBJECTIVE: To test the hypothesis that selective >serotonin reuptake inhibitor (SSRI) >antidepressants may have a suicide...
> This type of study is great, although this type of research is preliminary.
It was a retrospective study of existing information. I don't know what could be more informative.
> >Psychotropics and suicide prevention. >Implications from toxicological screening of >5281 suicides in Sweden 1992-1994.
> There is another problem with these studies. They are testing levels of antidepressants within the blood of suicide victoms. This type of study is not geared to reveal any great association because you have a large group of untreated people pooled in which may downplay an association. There needs to be a double blind trial comparing suicidal tendancies induced by placebo vs. active SSRI.
Did you read the full-text studies I linked with? The third one answers that question.
> >Increasing homicide rates and linoleic acid >consumption among five Western countries, 1961->2000.> Thats great. This points to the idea that dietary deficiancy or functional deficiancy of n-3 polyunsaturated fats may lead to increased suicide.
No, it shows that excess omega-6 leads to homicidal violence.
> I don't know, does Tracy recommend elminating omega 3 in favor of O-6 ?
> Linkadge
Dude, Tracy recommends these oils:
http://www.essentialoiltherapies.com/prodInfo_blends.html
Refer back to my first post in this thread, and go to the quotations numbered 16 and 18. Her treatment is called aromatherapy. These are not dietary fats.
Nothing against aromatherapy, but it isn't going to heal serious mental illness.
And, by the way, sesquiterpene oils rubbed on the feet do not clear that gummy gooey stuff out of the brain, as she claims.
I'm done with this thread.
Posted by Larry Hoover on December 16, 2005, at 21:13:48
In reply to Re: Dr. Tracy on SSRIs.., posted by linkadge on December 16, 2005, at 20:06:15
> >Maybe. Placebo response is the bugbear of mood >disorder treatment. Placebo response in e.g. >positive symptom schizophrenia is estimated at < >3%. Here is an excellent article about the >difficulties in interpretation that arise >because of the clinical trial system for >medication being inappropiate for mood disorder >treatments.
> When you have a drug that is oftentimes performing no better than placebo, you'd better make sure it is safe. Thats what sparks this contoversy, the combination of questionable efficacy, and questionable safety.
Fine. Let's just keep using tricyclics, which on every measure, come up worse than SSRIs.
> I don't think you have bipolar disorder, do you ?No, I do not. Unless you accept other nosologies, where AD-induced mania is a form of bipolar.
>>That's why they did these studies. Healy's an author on the first one.>>A meta-analysis of 702 clinical trials....
>>http://bmj.bmjjournals.com/cgi/content/full/330/7>488/396>"Discussion Our systematic review, which included a total of 87 650 patients, documented an association between suicide > attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials."
> >And, another, of 477 more....
>> http://bmj.bmjjournals.com/cgi/content/full/330/7>488/385> "Increased risks of suicide and self harm caused by SSRIs cannot be ruled out"
> Thanks, that saves me the trouble.What, of reading them?
From the first of those two:
"In comparing fatal suicide attempts, we did not detect any differences between SSRIs and placebo (0.95, 0.24 to 3.78). "From the second one:
"The pooled odds ratio (with 95% credible intervals) for all SSRIs compared with placebo treated subjects in relation to suicide was 0.85 (0.20 to 3.40)."Considering that a clinical trial seldom exceeds 10 weeks, and the critical danger period for suicidal act is most definitely within these ten weeks, the failure to discover any evidence for an increase in suicide would tend to fail to support your/Tracy's hypothesis. One could fairly argue that the SSRIs were modestly protective against suicide.
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