Posted by PaulB on August 24, 2001, at 15:55:55
In reply to Re:SP Cocktail/Mechanisms of Action/Memory Culprit » PaulB, posted by Rick on August 23, 2001, at 21:54:54
>Rick:
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> >Its good to have your feedback. Just for the record I have no experience with Provigil or Serzone but take Klonopin and am interested in this drug.
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> I think it's worth remembering, though, that an understanding of social phobia in physiological terms is just now beginning.
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> >I think your probably right. Since SP has moved up the ranks to becoming the third largest mental health problem in the world inevitably drug companies are going to devote more time and resources to understanding SP and developing drugs that can be used for it.
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And from the research and expert postulating I've seen, it looks as if the etiology will prove to be extremely heterogeneous. Besides, treatments that shouldn't work in theory often end up working very well (and certainly vice versa, too). This led me back to Thomas Kramer's wonderful “jolt the system” article on “Mechanisms of Action” in Medscape. At the beginning of the essay, he wisely states:
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> “The question of putative mechanisms of action continues to haunt psychopharmacology. Put simply, we know these drugs work, but we have very little idea how. We make guesses based on the neurochemical effects of these compounds. We have very little proof, and sometimes very little data, about whether the neurochemical effects that we find have anything to do with the therapeutic effect of the medication.”
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> He then talks about a European serotonin reuptake *enhancer* (!) that defies all logic by working well for depression.
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> >Often it can be the case that drugs not indicated or being tested for a particular disorder may be effective for another. A classic example is the introduction of the first class of antidepressants, the MAOI's. They were originally given to people suffering from tuberculosis. Their original purpose was to kill the germ that causes this illness, but doctors soon found that it made depressed people-who were still very ill with TB-feel more cheerful. Research showed it was the drugs effect on the monoamines that caused this and thus the beginning of the monoamine antidepressant revolution followed. I have also read of that particular serotonin re-uptake enhancer that is only available in Europe, France, I believe. In this case I think there is a clear rationale why such a drug may be beneficial for depression. It may help kick-start the cycle that is disfunctional in depressives. It is interesting that one of the drawbacks of the SSRI's is that by blocking the re-uptake pump they prevent serotonin from floating back into the neuron from which it is released which is why, some say, people can relaspse on these drugs.>When you say, "I was less enthusiastic about Provigil," are you saying that you used it and was dissatified, or are you saying that its properties don't make sense for anxiety (or both)? Klonopin and Provigil work very nicely together for me, and regarding Serzone's potentiating effect, note that I'm taking about half as much Klonopin as I needed when my only other med was Celexa (and this was before Provigil was added with its stimulating effects). Who knows, concomitant Klonopin and Prvigil may not work for anyone besides Craig and I, but I am ever so grateful I hit on my combo.
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> >When I said I was less enthusiastic about Provigil I meant in reference to its use to eliminate or reduce the cognitive side-effects of Klonopin which is what, in this instance it was being suggested for and not as a concomitant medication for SP. I know there has been a lot written here at PB about the possibility that Provigil and its older analogue Adrafinil may be effective for SP. There was a really long list of postings not long ago debating whether dopamine was disfunctional in SP. Outside of PB I have yet to come across evidence or opinion that medicines that enhance dopamine are helpful for SP. There was one example though, in reference to Parnate, whose added 'noradrenergic and dopaminergic effects' make it superior to Nardil for SP. I know people will disagree here because there is no question that Nardil has similar effect and Nardil is often considered superior to Parnate?
NG-D 97-1 sounds extremely promising and exciting. AS for the bz anxiety-receptor specific alluded to, it sounds as if benzo originator Roche is in the early stages of working on something with such a proile (press release:
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> http://www.roche.com/med-corp-detail-2000?id=21).
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> >I agree with you that NGD 97-1 sounds extremely promising. Why, if newer anxiolytics are being developed that are selctive unlike Klonopin. Because Klonopin will probably always be one of the 'gold standard' drug treatments for SP due to it pharmacological profile-bz receptor binding tightness, half-life, possible serotonin properities and if we can eliminate those unwanted, troublesome side-effects then thats great.
>Other psycho-babblers suggested Xanax(Judy1) and Provigil(AndrewB). From my experience there is a difference in the level of cognitive impairment and memory problems induced by these two drugs. Xanax causes fewer problems and it is a marked difference.
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> Are you saying that Provigil causes more memory decline than Xanax?? Or are you indirectly referring back to Klonopin? Regardless, I was surprised to see some recent complaints about memory loss from Provigil, given that it's often viewed as a nootropic memory-enhancer. But I notice that the Provigil monograph does mention some incidence of memory impairment (subjective?) relative to placebo. (Don't know if it's significant.) Now THAT got me thinking...
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> > I was indirectly referring back to Klonopin.
Provigil may be an alpha1 adrenergic agonist. This particular norepinephrine receptor is coupled with vigilance, memory and attentiveness.
Playing around with it with Provigil should bring about positive changes but I suppose some degree of tolerance may occur or inital unresponsivness as seen with convnetional antidepressnats. I know less about Provigil so I dont know.It's well known that Klonopin can cause episodic amnesia, though not necessarily in everyone. And it's well known that Serzone and other AD's can cause this too, although some of that might be attributable to unresolved depression or inaccurate subjective assessment of memory. Sorry about jumping back and forth here...but since it's unlikely I have more Klonopin in my bloodstream than pre-Serzone (remember, I was taking more K then), wouldn't the amelioration of memory loss upon temporary Serzone discontinuation implicate Serzone as the source of my memory impairment, rather than Klonopin?
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> >I wouldnt think so. Discontinuing Serzone means stopping the inhibition of the CYP3A4 enzyme. This means Klonopin can be metabolised again and levels would decrease to much lower than combined Serzone-Klonopin. Even if you were taking more K before Serzone theres no way it would reach plasma levels that would be obtained by K+ Serzone at even high dosages because its extensively metabolised and INCREASINGLY metabolised dont forget.Related to that question, here's one thing I've long wondered. Perhaps that sole Klonopin user who has managed to get to this point in my rambling might be able to offer up some thoughts: Specifically, assuming X amount of Klonopin can lead to amnesic effects in someone, can it take a full year or more for this effect to surface? I had minimal memory deficit (it's still not huge, just inconvenient) for the full year that I took 2-3 mg Klonopin minus any AD.
> >I am not sure. But you mention that you took Klonopin for a full year at 2-3mgs with minimal memory deficits. If the releif in SP symptoms was satisfactory then wouldnt it be okay without further augmentation with another drug, esp one that causes drug-drug interaction with K?
Hope all is well and thanks for the links.
PaulB
poster:PaulB
thread:36517
URL: http://www.dr-bob.org/babble/20010822/msgs/76256.html