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
poster:linkadge
thread:587690
URL: http://www.dr-bob.org/babble/20051211/msgs/589586.html