![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 37 to 61 of 61. Go back in thread:
Posted by PaulB on August 23, 2001, at 15:29:35
In reply to Re: SP Cocktail - Your Questions+Surprise Enhancer (?) » rick_number1001@yahoo.com, posted by Rick on August 19, 2001, at 16:26:43
> This post was far too long I though for me to try and continue it and for others to then make sense of it so I decided to reflect on it instead and all the issues, and there are alot which I thought were very interesting.
The issue of Klonopin and memory impairment came up again. It can certainly be a problem. I raised the issue myself a while back and at the time Mr Richelson was answering questions at PB.[ http://www.dr-bob.org/babble/20010411/msgs/59594.html ] I wondered if there were any selctive GABA antogonists that could be used to eliminate not only the memory impairment induced by Klonopin but also the annoying cognitive impairment. Looking back I realise I should have asked whether there were any selective bz 'omega' antagonists. His response was that he was not aware of any such drugs available or in clinical trials but there were drugs that were specific only for the bz receptor that regulates anxiety. Pagoclone is a forerunner. However, there is actually an 'inverse agonist', selective for the bz receptor that regulates memory and cogntive function! It is being developed by Neurogen, has just entered phase 2 trials, is indicated for Alzheimers disease and is curreently referred to as NGD 97-1. Neurogen really has their finger on the pulse when it comes to the understanding of and development of new GABA drugs. A trip to their website will reveal more.
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. I was less enthusiastic about Provigil for two reasons. Firstly it seemed an approach that would attempt to correct the problem by stimulating the brain with increased catecholamine activity. I didnt think this was very practical and secondly Provigil has potent effect on Glutamate. I thought this may interfere with the effectiveness of Klonopin or Klonopin's activity.
It was mentioned that discontinuation of Serzone seemed to attenuate the memory impairment of Klonopin. This doesnt surprise me. I believe Serzone would have a much greater impact on plasma levels of Klonopin than Klonopin alone, if you take in mind that Klonopin is metabolised by the isoenzyme CYP3A4 and Serzone potently inhibits this enzyme in the liver.
On Klonopin and serotonin, I agree that it could increase or decrease its levels. One metabolite of Klonopin is serotenergic but then Klonopin, via its enhancment of GABAA activity suppresses serotonin activity, although this is probably regionally specific. This is why I believe Klonopin shouldnt be viewed as a drug that is always likely to cause a depression.
PaulB
Posted by Rick on August 23, 2001, at 21:54:54
In reply to Re: SP Cocktail - Your Questions+Surprise Enhancer (?), posted by PaulB on August 23, 2001, at 15:29:35
Paul -
Interesting thoughts.
I think it's worth remembering, though, that an understanding of social phobia in physiological terms is just now beginning. 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:
“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.”
He then talks about a European serotonin reuptake *enhancer* (!) that defies all logic by working well for depression.
If you’d like to read the whole article – highly recommeded – go to:
http://www.medscape.com/medscape/psychiatry/journal/2001/v06.n01/mh0116.kram/226620.html
(Free but requires simple registation; medical credential NOT required.)But I will include his conclusion here:
“The crucial point in any discussion of mechanisms of action of psychotropic medication is to maintain a healthy respect for our ignorance. Fundamentally, we have no idea how these medications work. It is the nature of high-quality scientific discourse to postulate plausible theories and try to prove or disprove them. When any currently accepted theory no longer explains all of the data, it must be either modified or discarded. Psychopharmacology has had its share of discarded theories. We once thought that schizophrenia was exclusively a disease of dopamine and that depression was exclusively a disease of deficit of either serotonin or norepinephrine. Lately, we have been focused on the idea that "less is more" as far as the mechanisms of action of our medications. It is certainly true that as we have developed medications with less side effects, patients are more likely to take them regularly and stay on them, and, as such, these newer medications have more effectiveness than older ones. We must always remember, however, that until we figure out exactly what psychiatric illness is on a neurochemical level and what medications that seem to make it better actually do, all mechanisms of action for any effective medication may have potential benefit.” (Not surprisingly, Kramer also wrote an insightful defense of polypharmacy: http://www.medscape.com/medscape/psychiatry/journal/2000/v05.n03/mh0509.kram/mh0509.kram.html )
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.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:
http://www.roche.com/med-corp-detail-2000?id=21).
> 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.
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...
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?
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.
Thanks for the great food for thought.
Rick
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:
>
> >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.
>
> I think it's worth remembering, though, that an understanding of social phobia in physiological terms is just now beginning.
>
> >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.
>
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:
>
> “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.”
>
> He then talks about a European serotonin reuptake *enhancer* (!) that defies all logic by working well for depression.
>
> >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.
>
> >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:
>
> http://www.roche.com/med-corp-detail-2000?id=21).
>
> >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.
>
> 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...
>
> > 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?
>
> >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
Posted by Lorraine on August 25, 2001, at 17:01:55
In reply to Re:SP Cocktail/Mechanisms of Action/Memory Culprit » PaulB, posted by Rick on August 23, 2001, at 21:54:54
> > >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:
>
> “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.”
>
> He then talks about a European serotonin reuptake *enhancer* (!) that defies all logic by working well for depression.
>
> If you’d like to read the whole article – highly recommeded – go to:
> http://www.medscape.com/medscape/psychiatry/journal/2001/v06.n01/mh0116.kram/226620.html
> (Free but requires simple registation; medical credential NOT required.)
>
> But I will include his conclusion here:
>
> “The crucial point in any discussion of mechanisms of action of psychotropic medication is to maintain a healthy respect for our ignorance. Fundamentally, we have no idea how these medications work. It is the nature of high-quality scientific discourse to postulate plausible theories and try to prove or disprove them. When any currently accepted theory no longer explains all of the data, it must be either modified or discarded. Psychopharmacology has had its share of discarded theories. We once thought that schizophrenia was exclusively a disease of dopamine and that depression was exclusively a disease of deficit of either serotonin or norepinephrine. Lately, we have been focused on the idea that "less is more" as far as the mechanisms of action of our medications. It is certainly true that as we have developed medications with less side effects, patients are more likely to take them regularly and stay on them, and, as such, these newer medications have more effectiveness than older ones. We must always remember, however, that until we figure out exactly what psychiatric illness is on a neurochemical level and what medications that seem to make it better actually do, all mechanisms of action for any effective medication may have potential benefit.” (Not surprisingly, Kramer also wrote an insightful defense of polypharmacy: http://www.medscape.com/medscape/psychiatry/journal/2000/v05.n03/mh0509.kram/mh0509.kram.html )I think we should all print these two paragraphs out and post them on our computers. They are humbling. And, everytime, I think we know a thing or two, I try to remember how little we know.
Lorraine
Posted by Rick on August 28, 2001, at 20:35:45
In reply to Re:SP Cocktail/Mechanisms of Action/Memory Culprit » Rick, posted by Lorraine on August 25, 2001, at 17:01:55
>I think we should all print these two paragraphs out and post them on our computers.
Well, maybe on my *home* computer. My med cocktail for social phobia hasn't eliminated THAT much inhibition :)
Seriously, I'm glad you found Kramer's thoughts as wise and relevant as I did.
Rick
Posted by Rick on August 28, 2001, at 20:37:13
In reply to Re:SP Cocktail/Mechanisms of Action/Memory Culprit, posted by PaulB on August 24, 2001, at 15:55:55
Paul:
Once again, you’ve provided some interesting reading and insightful thoughts, although I have a different perspective on some of the subtopics.
>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?
If anyone can vouch for the fact that dopaminergic agents can be problematic in social phobia rather than helpful, it’s me! My experiences with with dopamine-based treatments and augmentors have ranged from bad to awful (the latter represented by solo seligiline at 10-15 mg – yikes!) No one really has a solid handle on Provigil’s pharmacology. The manufacturer flatly states that it posseses little in the way of either dopaminergic OR adrenergic activity. That may be overstated. I’ve seen conflicting studies. But one thing that does NOT seem to be controversial is the conclusion that Provigil’s effects appear to be mediated in very limited areas of the brain -- quite unlike Ritalin or amphetamines, which have widespread activity. This assertion, plus the related positioning as a "more gentle" kind of stimulant, drove my interest in trying Provigil as an augmentor after other stimulating meds made me nervous. And – at least combined with Serzone and 1 mg Klonopin – I got the non-wired stimulation effect I was looking for...plus wonderful and unanticipated psychic benefits (further reduction in anxiety – as long as the dose is optimized -- plus enhanced confidence, enthusiasm, and sociability).
> >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?
>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.
Interestingly, I found some information indicating that Provigil/modafinil is an inducer of CYP3A4, which should reverse at least some of Serzone’s CYP3A4 inhibition, shouldn’t it? Wouldn’t this mean that Serzone’s potentiation of Klonopin is then reduced as well? On a side note, Provigil is actually metabolized in part by CYP3A4, which means it can induce its own metabolism to some degree. Even though this supposedly happens only at higher doses, I sometimes wonder if that’s why every so often Provigil seems to lose it’s “oomph”, which is quickly remedied by a day or two at double-dose. Now, to complicate things even more, if Serzone is a stronger inhibitor of CYP3A4 than Provigil is as an inducer, does this mean that Serzone could potentiate Provigil, too? This is all very circular and confusing to me, but whatever interactions are going on seem to be beneficial for my Social Phobia treatment...although there could still be some negative impact cognitively, I suppose. Regardless, it works for me, and my liver enzymes remain right where they should be. (I wonder if the same would be true of adrafinil, whose manufacturer recommends quarterly hepatic function tests even when used as monotherapy?)
> >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?
I’m not inclined to head back to the Klonopin monotherapy that gave me a (completely subjective ) 65-70% improvement, when the current cocktail gives me 90% with a more multidimensional effect. And for whatever reasons, my vital physical signs like blood pressure and fasting glucose have gone from adequate to excellent since I started the combo – while, as I mentioned, hepatic function remains unaffected by the putative drug interactions.
Now, if the memory effects were to go from moderately bothersome to worse, I could reconsider. I do understand your reasoning on this topic, but I have a strong sense that, for me, the Serzone in and of itself is *at least* as much a culprit as the low-dose Klonopin (even if the K IS extensively potentiated). Maybe I have an attention bias towards anecdotal reports that talk about meds I personally use, but Serzone seems to receive a lot more than its fair share of cognitive-impairment complaints.
Thanks again for the helpful and interesting thoughts.
Rick
Posted by kregpark@yahoo.com on September 3, 2001, at 2:43:13
In reply to Re:SP Cocktail/Mechanisms of Action/Memory Culprit » PaulB, posted by Rick on August 28, 2001, at 20:37:13
On dopamine: (Finally Bill I *think* I might disagree with you on something here !! :)
> 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?
>I believe that in many moderate to severe cases of SP dopamine plays a role:
Studies:
Nardil boosts serotonin and dopamine (granted dopamine to a lesser extent).
Klonopin tends to "stablize dopamine levels" as it is often used as a 2nd liner for bipolar swings.
Klonopin tends to induce depression with antiserotonin effects, possibly suggestive of enhanced dopamine function in certain brain regions (Davidson - 1992?)
2 studies show low D2 function in social phobics.Personal experiences:
*Good drugs for me at least short term*
1) On acute basis, Dexedrine very prosocial. (never tried chrnoically)
2) On actue short term Ritalin very prosocial (less than dexedrine, far shorter lasting prosocial effect, no 5ht increase).
3) *Amineptine* *very* prosocial and prosexual on acute basis (where it acts primarily as selective D2 dopamine enhancer), unfortunately becomes large noradrengeric in chronic use.
4) Nardil of course
5) Parnate when add low dose Xanax.
6) Eldepryl low dose with Remeron and add low dose Xanax.
7) PROVIGIL GOOD ANYTIME ALL THE TIME !!!*Not so good dopaminergics for me:*
1) amantadine - reduction of Nardil benefit (but proenergy, prosexual)
2) mirapex (pramipexole) - depressive somewhat - is d3 selective which is not a good predictor of success based on research )* in between *
1)Wellbutrin (depends what I took it with)
With Xanax or tramadol very effective.
With SSRI's not effective (anti-sp)
With Nardil in low dose *EFFECTIVE* - MUCH LIKE PROVIGIL IF DOSE LOW.have been prosocial in my case.
Also amineptine *very* prosocial prosexual on acute basis (where it primary action is very selective dopamine enhancement)
Unfortunetly on chronic basis amineptine becomes much more noradrenergic.
Posted by kregpark@yahoo.com on September 3, 2001, at 3:00:15
In reply to Re:SP Cocktail/Mechanisms of Action/Memory Culprit » Rick, posted by kregpark@yahoo.com on September 3, 2001, at 2:43:13
Provigil and dopamine:
1) If provigil is NOT dopaminergic, I believe
it would be the only potent wakeful agent
that does not enhance dopamine function.
(gaba inhibitor would do this but would
of course enhance dopamine and other
neurotransmitter function)Dopamine studies in rats:
1) "Social leaders" among rats have highest dopamine levels.
2) "Most passive" rats have lowest dopamine levels
3) Rats general socialability directly linked to dopamine levels.
4) Rats sexual activity and "success" positively correlated to dopamine levels.
Dopamine and rejection sensivity:Atypical Depression has a key feature of high sensitivity to rejection.
(Social phobia also has this as a key feature).
BOTH condition respond VERY WELL to Nardil, BUT
do NOT respond (especially SP) to tricyclics.
The known difference is a lack of dopaminergic
effect in tricylics (Liebowitz)I will add a few links later at http://socialfear.com
There is a nice abstact quite recent called suggesting
that serotonin, dopamine, and gaba probably all play a
role in a substantial number of SP cases.
Posted by kregpark@yahoo.com on September 3, 2001, at 3:13:03
In reply to Re:SP Cocktail/Mechanisms of Action/Memory Culprit » Rick, posted by kregpark@yahoo.com on September 3, 2001, at 2:43:13
More on dopamine and SP:
ECSTACY (MDMA) VERSUS COCAINE.
Both Ecstacy and cocaine potently enhance dopamine function.
After the very short term:
1) Cocaine becomes DA++, NE++, and axiogenic.
2) Ecstacy becomes 5ht++, DA++, and PROSOCIAL.(I have used neither agent BTW:
Probably not a good mix with Nardil!!! :)Anyway, I don't believe there is any drug known
to more predictably prosocializing than Ecstacy.
And to reiterate, it's potent action is quite
specific to potent DOPAMINE + SEROTONIN enhancement.
Posted by Rick on September 3, 2001, at 4:18:29
In reply to Dopamine and SP: a bit more, posted by kregpark@yahoo.com on September 3, 2001, at 3:00:15
Lots of interesting observations in your two posts on dopamine and social phobia/meds!
There IS one area where my viewpoint differs strongly from yours. Ironically, the disagreement stems from something we *agree* on, namely that Klonopin is very effective for Social Phobia. Before going on, please understand that I'm not actually disagreeing with *you* per se, but with something you briefly praised in a post earlier in this thread. (OK, I'm probably confusing you and any other readers thus far ...just read on and you'll understand.)
The disagreement surrounds your thanking Dr. Bob for including the Brazilian study on Klonopin in Social Phobia on his site. In my view, the fact that this article remains here is perhaps my major "beef" with Dr. Bob's site, for a number of reasons.
First of all, the article is becoming dated. Nothing wrong with that in and of itself, but it seems as if the "Social Phobia" link is just languishing there with no real attention given to it. It's basically an anecdotal report, not a rigorous study of any kind, when in fact several excellent and even pivotal studies on Klonopin for SP -- some of them placebo-controlled -- do exist. Heck, the Brazilian write-up even ends by saying their approach is under review! So, what did the review conclude??
Secondly, it does a disservice by dwelling on supposed Klonopin-driven disinhibtion episodes that I'm sure are not very typical. Some uninformed people who take that article at face value will probably stay away from Klonopin because they fear a personality change that will turn them into gun-toting gangsters like that one social phobic-turned-thug the authors cite.
Worst of all is the article's claiming 3-6 mg/day as the typical effective dosage range for Klonopin in Social Phobia. Frankly, I find it bordering on irresponsible to leave an article on the site that cites a MUCH higher than typical range as "average". Certainly , there are more than a few people who do better on a higher dose (I believe you said you take about 4 mg yourself -- which is still a lot less than 6), but any cursory review of posts on this board or others, or discussions with medical professionals, will tell you that most people do best on 3mg or less, and that a great many do just fine on 1 mg/day or less. And yes, I realize that body weight can make a difference, and that perhaps Brazilian clonazepam is less potent as a poster once suggested (although I tend to doubt that's the case).
I myself quickly ramped to 3 mg/day based on Dr. Davidson's 1994 placebo-controlled study of Klonopin, and fortunately discovered that I actually did a lot better-- and with virtually no sedation -- on 1.75-2.00. (Dr. Davidson's follow-ups showed that people tended to reduce their doses after awhile -- quite contrary to the popular "tolerance" beliefs -- and my own personal experience over two years mirrors that finding).
I wonder how many people ended up latching onto that article and ended up either unnecessarily over-medicating themselves or, worse yet, rejecting the very med (Klonopin) that could have helped them so much, simply because they felt doped up on a "typical dose" recommended by the authors. (Interestingly, Roche, maker of Klonopin, says that going from 2mg/day to 3mg does not generally confer additional benefit in Panic Disorder, one of Klonopin's two FDA-approved indications.)
I guess the fact that the article may have led some Social Phobics to that wonderfully-helpful med is a good thing, but I wish it could be done in a more enlightened fashion.
In summary, *some* people do need the 3-6 mg rangeof daily Klonopin given in the article, but citing a "low-end" dose that's too HIGH for *most* Social Phobics is doing a disservice!
I've posted about this several times over the last few years, and I'm dismayed to see that the "Social Phobia" link on this site still leads to that misleading and almost sensationalistic article. Better to remove the SP link altogether.
OK, I'm off my soapbox now.
Rick
Posted by Mitch on September 3, 2001, at 9:47:44
In reply to Re: (Dopamine and SP... and) a *Complaint* » kregpark@yahoo.com, posted by Rick on September 3, 2001, at 4:18:29
What about a combination of
1) Klonopin
2) low dose SSRI
3) low dose pergolide (D2 agonist)?
Posted by Rick on September 3, 2001, at 12:10:33
In reply to Re: (Dopamine and SP) » Rick, posted by Mitch on September 3, 2001, at 9:47:44
> What about a combination of
> 1) Klonopin
> 2) low dose SSRI
> 3) low dose pergolide (D2 agonist)?
Well, I'm just guessing here and the usual inter-person unpredictability applies. But 1+2 sounds good, although -- contrary to the typical doc-prescribed regimen, I'd start the K first.I once tried pergolide (Permax) as an augmentor to Klonpin (with no AD). A friend had tried it for periodic limb movements of sleep, and it it turns out simply increasing her [nighttime-only] Neurontin dose worked a lot better, and without the nasal congestion and other side effects of pergolide.)
So I tried adding some to my Klonopin. Maybe I popped too much pergolide on the first trial (I know you're supposed to ramp up slowly, but I wasn't all THAT much higher than recco'd amount. That was dumb, nonehelsess.) Anyway, it was a disaster, and I dumped it very quickly. (The movie I saw immediately after taking my first and only dose of Pergolide was punishment enough, without having to feel like I had sudden-onset flu at the same time!)
Given this experience, I wasn't at all to find a new study that showed Pergolide so ineffective in Social Phobics that the study was promptly killed. Here's the Medline listing in case you want to order the short article or search for more info. (There's no abstract).
Depress Anxiety 2000;11(1):45-47 Related Articles, Books, LinkOut
Treatment of social phobia with the dopamine agonist pergolide.Villarreal G, Johnson MR, Rubey R, Lydiard RB, Ballanger JC.
Publication Types:
Clinical trial
Letter
Posted by Rick on September 3, 2001, at 13:44:37
In reply to Re: (Dopamine and SP), posted by Rick on September 3, 2001, at 12:10:33
Posted by Mitch on September 3, 2001, at 15:48:33
In reply to Re: (Dopamine and SP), posted by Rick on September 3, 2001, at 12:10:33
> > What about a combination of
> > 1) Klonopin
> > 2) low dose SSRI
> > 3) low dose pergolide (D2 agonist)?
>
>
> Well, I'm just guessing here and the usual inter-person unpredictability applies. But 1+2 sounds good, although -- contrary to the typical doc-prescribed regimen, I'd start the K first.
>
> I once tried pergolide (Permax) as an augmentor to Klonpin (with no AD). A friend had tried it for periodic limb movements of sleep, and it it turns out simply increasing her [nighttime-only] Neurontin dose worked a lot better, and without the nasal congestion and other side effects of pergolide.)
>
> So I tried adding some to my Klonopin. Maybe I popped too much pergolide on the first trial (I know you're supposed to ramp up slowly, but I wasn't all THAT much higher than recco'd amount. That was dumb, nonehelsess.) Anyway, it was a disaster, and I dumped it very quickly. (The movie I saw immediately after taking my first and only dose of Pergolide was punishment enough, without having to feel like I had sudden-onset flu at the same time!)
>
> Given this experience, I wasn't at all to find a new study that showed Pergolide so ineffective in Social Phobics that the study was promptly killed. Here's the Medline listing in case you want to order the short article or search for more info. (There's no abstract).
>
> Depress Anxiety 2000;11(1):45-47 Related Articles, Books, LinkOut
>
>
> Treatment of social phobia with the dopamine agonist pergolide.
>
> Villarreal G, Johnson MR, Rubey R, Lydiard RB, Ballanger JC.
>
> Publication Types:
> Clinical trial
> Letter
>
>
>
>
That's interesting that a study was even considered! My pdoc actually tried some of that a year ago not really for SP, but to help relieve dystonia from the SSri I was already taking and see if my ADHD would improve (without pstims). It *did* relieve the dystonia AND improved my ADHD symptoms, but it aggravated the nausea I was having with Sri so much it didn't turn out to be worth bothering with. I guess what I am curious about now would be what if I took Pergolide with a little *Remeron* and an SSRi? Given that Remeron is a 5HT-2 and 5HT-3 antagonist perhaps I wouldn't get the nausea from the Pergolide, I wouldn't get the dystonia from the Ssri and ADHD and SP symptoms would be improved. (?)
Posted by kregpark@yahoo.com on September 5, 2001, at 1:44:34
In reply to Re: (Dopamine and SP... and) a *Complaint* » kregpark@yahoo.com, posted by Rick on September 3, 2001, at 4:18:29
Interesting post Rick!
I see your points. I agree with some and I also
kind of still like the Versiani article.
I guess I still like the
article simply because it seems to me a "classic"
and I think still mostly accurate. I think the
upper range of 6mg is ok (I took 5 at times without
problem with Zoloft + Serzone) - but the low end
could probably be 1 or 2.Some points like "disinhibition" I definitely
experinced myself. Even Gorman's classic book
points out disinhibition citing examples such
as "arguing with the boss" and "driving recklessly"
I myself have done the former (a few times during
washouts of MAOI's!!! while on Klonopin alone!!)
and once did drive a bit recklessly when out a long
time at night and taking a bit too much Klonopin
early in my fantastic discovery of it.I think panic disorder patients probably use less
with good results than SP - different disorders.Also, I think that those taking *solely* Klonopin
alone will get by with a bit of a lower dose. Mine
didn't vary more than about 20% though alone versus
in combos.I think in my case that some drugs either "add"
to the effective Klonopin effect. Examples for
me coming to mind are Provigil or Prov+Serzone, and
Gabapentin. Tramadol also comes to mind.Provigil seems unique to me that it has stimulant
effects and seems to boost the effect of a given
Klonopin dose without the expected side effects
of that dose.I have experienced it before though - in the short
run, with Ritalin and Dexedrine, both strongly
dopaminergic.Craig
> First of all, the article is becoming dated. Nothing wrong with that in and of itself, but it seems as if the "Social Phobia" link is just languishing there with no real attention given to it. It's basically an anecdotal report, not a rigorous study of any kind, when in fact several excellent and even pivotal studies on Klonopin for SP -- some of them placebo-controlled -- do exist. Heck, the Brazilian write-up even ends by saying their approach is under review! So, what did the review conclude??
>
> Secondly, it does a disservice by dwelling on supposed Klonopin-driven disinhibtion episodes that I'm sure are not very typical. Some uninformed people who take that article at face value will probably stay away from Klonopin because they fear a personality change that will turn them into gun-toting gangsters like that one social phobic-turned-thug the authors cite.
>
> Worst of all is the article's claiming 3-6 mg/day as the typical effective dosage range for Klonopin in Social Phobia. Frankly, I find it bordering on irresponsible to leave an article on the site that cites a MUCH higher than typical range as "average". Certainly , there are more than a few people who do better on a higher dose (I believe you said you take about 4 mg yourself -- which is still a lot less than 6), but any cursory review of posts on this board or others, or discussions with medical professionals, will tell you that most people do best on 3mg or less, and that a great many do just fine on 1 mg/day or less. And yes, I realize that body weight can make a difference, and that perhaps Brazilian clonazepam is less potent as a poster once suggested (although I tend to doubt that's the case).
.... >
> Rick
Posted by kregpark@yahoo.com on September 5, 2001, at 1:57:55
In reply to Re: (Dopamine and SP) » Rick, posted by Mitch on September 3, 2001, at 9:47:44
> What about a combination of
> 1) Klonopin
> 2) low dose SSRI
> 3) low dose pergolide (D2 agonist)?Mitch:
If I think pergolide is Cylert?
If so I understand it is 2nd to Ritalin in popularity
for ADD in children.Assuming we're talking about Cylert, my understanding
is it has advantages to Ritalin in a longer half life.
There is one side effect concering some doctors,
I think its to do with liver, I don't know much there.I think the combination sounds possibly very good,
though I agree with Rick. For myself I would start with
SSRI first, then add Klonopin.After evaultating that I'd consider the Cyclert.
I find dopaminergics tricky. A good doctor
is hard to find. Especially stimulants tend to
be "up and downers". The longer half life might help.A definitely believe they can be used though!!
Sometime I might want to try something like
Wellbutrin (it is similar to a stimulant) with
something to blunt NE and enhance serotonin, like
Xanax, or tramadol, or Serzone + sertonergic.
Posted by kregpark@yahoo.com on September 5, 2001, at 2:08:30
In reply to Re: (Dopamine and SP) » Mitch, posted by kregpark@yahoo.com on September 5, 2001, at 1:57:55
One more on DOPAMINE:
More evidence linking SP with low DOPAMINE:
Those with SP are 5 times more likely to
get Parkinson's in later life, according to
at least one large well done study I saw.Two studies looking at brains (Couldn't say how
the 2nd but first was MRI I think) showed SP
folks had dysufnctional (causing low dopamine)
D2 receptors in striatum in 1 study and don't
recall the other study exactly.SMOKING: 5 times lower rate of Parkinson's in
heavy smokers (lung cancer get them instead!!!)
This is well established in AMA books etc.CAFFIENE: Recent studies (made Newsweek cover or
was it US NW Report?) show more coffee each
day lower Parkinson's risk with heaviest coffee
drinkers 5 times LESS likely to get Parksinson's.
(I've always LOVED LOTS of caffiene - am I
self medicating low dopamine levels?)(Rick: I recall that you don't benefit much or
maybe negatively from caffiene? I thought you
mentioned some panic type symtoms occasionally
also? Anyway my comment was just that studies
show than PANIC DISORDER patients respond with
ANXIETY TO CAFFIENE and SOCIAL PHOBIA patients
(no panic disorder) DO NOT normally get anxiety.Also Panic Disorder responds to imipramine
(no DOPAMINE++, SP does not), but BOTH respond
to Nardil very well (similar to imipramine but
with DOPAMINE ++ ).KregPark
Posted by Mitch on September 5, 2001, at 11:28:09
In reply to DOPAMINE - SP and Parkinsons Disease, posted by kregpark@yahoo.com on September 5, 2001, at 2:08:30
> One more on DOPAMINE:
>
> More evidence linking SP with low DOPAMINE:
>
> Those with SP are 5 times more likely to
> get Parkinson's in later life, according to
> at least one large well done study I saw.
>
> Two studies looking at brains (Couldn't say how
> the 2nd but first was MRI I think) showed SP
> folks had dysufnctional (causing low dopamine)
> D2 receptors in striatum in 1 study and don't
> recall the other study exactly.
>I have heard something about that before. Given I have SP and ADHD, the dopamine connection makes a lot of sense to me. When I was taking Adderall (5mg/day), the ability to focus, SIT STILL, and *LISTEN* to other people was dramatic. I also was more interested in being around other people, but I felt edier and then I got panic attacks and it got stopped. Some say it had to do with the non-verbal contextual information coming off of others that probably set off the panic. It was just too overwhelming. That is akin to my difficulty understanding what a song is about or even most of the words in a song being garbled, or having to reread paragraphs because I just forgot what was going on, or having to ask somebody to repeat themselves 2 or 3 times. It is frustrating, I know (and my pdoc believes) I have ADHD, but I can't treat it with a firstline med because it makes my SP worse, although it flattened my mood cycling out. Maybe if I had been treated as a child I wouldn't be having these problems. I don't want to get Parkinsons, but I don't want to be miserable either.
Posted by Rick on September 6, 2001, at 1:29:47
In reply to DOPAMINE - SP and Parkinsons Disease, posted by kregpark@yahoo.com on September 5, 2001, at 2:08:30
> CAFFIENE: Recent studies (made Newsweek cover or
> was it US NW Report?) show more coffee each
> day lower Parkinson's risk with heaviest coffee
> drinkers 5 times LESS likely to get Parksinson's.
> (I've always LOVED LOTS of caffiene - am I
> self medicating low dopamine levels?)
>
> (Rick: I recall that you don't benefit much or
> maybe negatively from caffiene? I thought you
> mentioned some panic type symtoms occasionally
> also? Anyway my comment was just that studies
> show than PANIC DISORDER patients respond with
> ANXIETY TO CAFFIENE and SOCIAL PHOBIA patients
> (no panic disorder) DO NOT normally get anxiety.
>Craig -
Caffeine can make lots of people nervous, whether they suffer from a clincal anxiety disorder or not. So it only stands to reason that in a *caffeine-sensitive* person with Social Phobia, caffeine-induced jitters will aggravate somatic SP-driven symptoms. I've learned that I *am* prone to jitteriness when I ingest a substantial amount of caffeine, so cutting back helped improve the consistency of my SP treatment a moderate but noticeable amount. I do miss my caffeinated coffee on weekdays, but I don't like it that much without cream and sugar anyway -- which I try to avoid to keep my weight down (losing weight helped me lose anxiety). But I'm a lifelong Coke-a-holic, and still drink lots of regular Coke and plenty of caffeinated coffee on weekends. (That's how I motivate myself to eat well during the week..."just a few more days and then you can eat and drink whatever you want all weekend.")
But yes, from what I've read and heard, caffeine is a powerful anxiety-inducer in most people with Panic. In fact, I think the caffeine reaction is sometimes used as part of a differential for diagnosis between PD and other anxiety disorders.
Rick
Posted by kregpark@yahoo.com on September 6, 2001, at 1:29:54
In reply to Re: DOPAMINE - SP and Parkinsons Disease, posted by Mitch on September 5, 2001, at 11:28:09
Mitch:
Thanks for your input.
You are the first I've come across on the Internet
with both the SP and ADHD, but I wouldn't be
surprised if many people have both. You mentioned
mood swings and Cyclert helping that. Do you have
bipolar also? I saw an abstract suggesting some
possible strong similarities between bipolar
and SP. Would make sense to me, both are very
chronic disorders with the former clearly involving
dopamine dysfunction and SP with strong evidence
so far.Anyway, you mentioned the panic later on with
classic stimulants like Ritalin and Dexedrine
increase norepineprine dramatically,
(as does the stimulant like antidepressant Wellbutrin)Have you tried PROVIGIL yet??
I saw at least 1 study for AHDH which was positive
but it probably was a smaller initial type of
study. Also Parkinsons' patients respond well
to it for treatment related sedation, and it may
be useful in it's own right for Parkinsons.It is highly likely that you will have much less
panic symtoms with PROVIGIL than Ritalin, Dexedrine
or (I think) Cylert as I believe that's very similar
to Ritalin.kregpark
http://socialfear.com/
(sorry for the shameless plugs, I'm just trying
to see if my website will show up on a search
one day... :)
> I have heard something about that before. Given I have SP and ADHD, the dopamine connection makes a lot of sense to me. When I was taking Adderall (5mg/day), the ability to focus, SIT STILL, and *LISTEN* to other people was dramatic. I also was more interested in being around other people, but I felt edier and then I got panic attacks and it got stopped. Some say it had to do with the non-verbal contextual information coming off of others that probably set off the panic. It was just too overwhelming. That is akin to my difficulty understanding what a song is about or even most of the words in a song being garbled, or having to reread paragraphs because I just forgot what was going on, or having to ask somebody to repeat themselves 2 or 3 times. It is frustrating, I know (and my pdoc believes) I have ADHD, but I can't treat it with a firstline med because it makes my SP worse, although it flattened my mood cycling out. Maybe if I had been treated as a child I wouldn't be having these problems. I don't want to get Parkinsons, but I don't want to be miserable either.
Posted by Mitch on September 6, 2001, at 10:38:49
In reply to Re: DOPAMINE - SP and Parkinsons Disease » Mitch, posted by kregpark@yahoo.com on September 6, 2001, at 1:29:54
> Mitch:
>
> Thanks for your input.
> You are the first I've come across on the Internet
> with both the SP and ADHD, but I wouldn't be
> surprised if many people have both. You mentioned
> mood swings and Cyclert helping that. Do you have
> bipolar also? I saw an abstract suggesting some
> possible strong similarities between bipolar
> and SP. Would make sense to me, both are very
> chronic disorders with the former clearly involving
> dopamine dysfunction and SP with strong evidence
> so far.
>Yes, bipolarII was my first diagnosis 20 years ago, rapid cycling (there wasn't any distinction back then I think-but that best describes it now). The SP/panic became prominent a few years later. I have always had ADHD problems all the way back to 2nd grade. Anyhow, the BPII was the *official* dx, until I started changing pdocs around in the last 3 or 4 years. Then it got changed to ADHD. That is when I tried Adderall 5mg AM with Neurontin (100mg 3xdaily)-nothing else. My cycling interestingly flattened out and *disappeared*. I got rather quiet and attentive. I slept a very regular 7 hours at nite. I couldn't get over how well I could *listen* and I suddenly had this ability to plan things out and execute them in a stepwise fashion and be patient with the process. Interestingly, I *lost* the ability to juggle 3 or 4 things simultaneously (albeit in a half-ass fashion). But I was always somewhat edgy on the pstim and complained about anxiety, I was also a little "cold" towards others as well. We tried adding a tiny dose (.5mg/day) of Risperdal to the mix and I got dystonia and gait disturbances and it got stopped, about that time also I started to panic and I couldn't tolerate being around anybody I was so uptight. Then I got a thyroid tumor-so the Adderall got stopped and I was put on big doses of benzos to quell the panic and my dx was changed to SP. The thyroid tumor might have been just coincidental-since I have a family history of thyroid cancer. Strange, but writing this just now I realize the first panic attack I had was right after my pdoc (18 years ago)gave me 25mg/day of thorazine to help with some anger I was having. I had been taking it for a few weeks, then I had to change shifts-my sleep schedule got interrupted and the panic got triggered. The last big bout of panic (2 years ago) also occurred within 2-3 weeks on a low dose of a dopamine antagonist(!) Sorry for rambling on, but there is definitely a connection there.
Mitch
Posted by Rick on September 6, 2001, at 16:13:17
In reply to Re: DOPAMINE - SP and Parkinsons Disease » kregpark@yahoo.com, posted by Mitch on September 6, 2001, at 10:38:49
> > Mitch:
> >
> > Thanks for your input.
> > You are the first I've come across on the Internet
> > with both the SP and ADHD, but I wouldn't be
> > surprised if many people have both. You mentioned
> > mood swings and Cyclert helping that. Do you have
> > bipolar also? I saw an abstract suggesting some
> > possible strong similarities between bipolar
> > and SP. Would make sense to me, both are very
> > chronic disorders with the former clearly involving
> > dopamine dysfunction and SP with strong evidence
> > so far.
> >
>
> Yes, bipolarII was my first diagnosis 20 years ago, rapid cycling (there wasn't any distinction back then I think-but that best describes it now). The SP/panic became prominent a few years later. I have always had ADHD problems all the way back to 2nd grade. Anyhow, the BPII was the *official* dx, until I started changing pdocs around in the last 3 or 4 years. Then it got changed to ADHD. That is when I tried Adderall 5mg AM with Neurontin (100mg 3xdaily)-nothing else. My cycling interestingly flattened out and *disappeared*. I got rather quiet and attentive. I slept a very regular 7 hours at nite. I couldn't get over how well I could *listen* and I suddenly had this ability to plan things out and execute them in a stepwise fashion and be patient with the process. Interestingly, I *lost* the ability to juggle 3 or 4 things simultaneously (albeit in a half-ass fashion). But I was always somewhat edgy on the pstim and complained about anxiety, I was also a little "cold" towards others as well. We tried adding a tiny dose (.5mg/day) of Risperdal to the mix and I got dystonia and gait disturbances and it got stopped, about that time also I started to panic and I couldn't tolerate being around anybody I was so uptight. Then I got a thyroid tumor-so the Adderall got stopped and I was put on big doses of benzos to quell the panic and my dx was changed to SP. The thyroid tumor might have been just coincidental-since I have a family history of thyroid cancer. Strange, but writing this just now I realize the first panic attack I had was right after my pdoc (18 years ago)gave me 25mg/day of thorazine to help with some anger I was having. I had been taking it for a few weeks, then I had to change shifts-my sleep schedule got interrupted and the panic got triggered. The last big bout of panic (2 years ago) also occurred within 2-3 weeks on a low dose of a dopamine antagonist(!) Sorry for rambling on, but there is definitely a connection there.
>
> MitchMitch -
It doesn't work for everybody (lukewarm reception on this board, anyway), but based on all you've indicated, it sounds as if you might want to try low-dose Provigil as part of a cocktail with more trad'l SP meds. Even if it doesn't turn out to be a potent for ADD, it:
-- Has much less of a dopaminergic profile than
traditional stims, and has much more
localized activity in the brain.
-- Except at higher doses, it doesn't usually
cause anxiety. For me, it in fact adds a
whole new -- and very welcome -- dimension
to my Social Phobia treatment. As you know,
Craig can also attest to Provigil's benefits
in SP.
-- As Craig mentioned, some animal studies have
shown that Provigil may potentially
*prevent* or help treat Parkinson's
-- To the extent that BP really applies to you,
note that about half the patients in the small
study that showed Provigil as a powerful
AD-augmentor were BP.Have you by any chance already tried Provigil or its overseas cousin adrafinil?
BTW, I once saw an abstract where a doctor (or group of doctors) claimed to have determined that having a tremore side effect on an SSRI indicates that the patient is someone who will probably develop Parkinsons at some point (I think it WAS worded that strongly, can't swear to it). I'm a bit skeptical about this, at least in terms of the *degree* of correlation claimed.
Rick
Posted by Mitch on September 7, 2001, at 1:37:20
In reply to Re: DOPAMINE - SP and Parkinsons Disease » Mitch, posted by Rick on September 6, 2001, at 16:13:17
>
> Have you by any chance already tried Provigil or its overseas cousin adrafinil?No, I haven't. I have tried Permax and Mirapex. Liked the Permax better. May be retrying that one sometime soon. I will read up on the Provigil/Adrafinil
>
> BTW, I once saw an abstract where a doctor (or group of doctors) claimed to have determined that having a tremore side effect on an SSRI indicates that the patient is someone who will probably develop Parkinsons at some point (I think it WAS worded that strongly, can't swear to it). I'm a bit skeptical about this, at least in terms of the *degree* of correlation claimed.
>
> RickGee, say it isn't so, but I wouldn't be too surprised. Haven't got PD in the family, which is a plus. Just epilepsy, thyroid, ADHD, and bipolar though.
Posted by kregpark@yahoo.com on September 7, 2001, at 2:36:01
In reply to Re: DOPAMINE - SP and Parkinsons Disease » Rick, posted by Mitch on September 7, 2001, at 1:37:20
General comment: It is a pleasure to read these
posts! I've not looked at Internet group exchange
on SP for a couple years, and never before was a
big fan, but I am really learning a lot here on this
board! Very interesting and informative and
sharing posts. Thanks to everybody and I suppose
especially Dr. Bob for setting up (and even
monitering for rude comments like one I made!! :)
to help keep the board clean.)I'm tired but wanted to comment briefly on the
last posts...Mitch:
I have tried Mirapex also, those I'm never heard
of Permex ... Although my symtoms obviously are
much different overall from yours, I wanted to just
throw in my reaction to Mirapex. To me I did not
feel good when taking it in a starting very low
dose even (as recommended). Hard to describe; it
was sort of alerting and sedating at the same time
which makes no sense probably. Maybe something like
mentally alert and physically sedated or something.
Also queasy feeling which some dopaminergics can
cause. I was enthusiastic about trying it but
quickly lost interest and threw it away.Of course for lots of people it will be useful but
that was just my own experience as one with
primarily (if untreated) severe SP and probably dysthmia.I agree with Rick about the Provigil.
Rick's comment about the Provigil antidepressant
augmentation and particularly positive response in bipolar low
patients is right on. I recall that now after he
mentioned it. (I just happened to read that article
a few days ago.. it is one of the 10 or so journal
articles I have kept a copy of ... ) I would never
have thought of that though until Rick mentioned it.Very sleepy for a change ... (Nardil + Provigil
leads to 5.5 hours sleep for me on average),
so will stop here...kregpark
> >
> > Have you by any chance already tried Provigil or its overseas cousin adrafinil?
>
> No, I haven't. I have tried Permax and Mirapex. Liked the Permax better. May be retrying that one sometime soon. I will read up on the Provigil/Adrafinil
>
> >
> > BTW, I once saw an abstract where a doctor (or group of doctors) claimed to have determined that having a tremore side effect on an SSRI indicates that the patient is someone who will probably develop Parkinsons at some point (I think it WAS worded that strongly, can't swear to it). I'm a bit skeptical about this, at least in terms of the *degree* of correlation claimed.
> >
> > Rick
>
> Gee, say it isn't so, but I wouldn't be too surprised. Haven't got PD in the family, which is a plus. Just epilepsy, thyroid, ADHD, and bipolar though.
Posted by Marty on March 7, 2008, at 10:57:03
In reply to Re: DOPAMINE - SP and Parkinsons Disease » Mitch, posted by kregpark@yahoo.com on September 7, 2001, at 2:36:01
Hi guys,
Very interesting thread ! .. even in 2008. Would you care to give us an update of what you've learned since that 2001 thread ? The things you tried since 2001 and what you're looking for in the future ? .. Is there anything interesting in the pipelines for us SP sufferers ?
/\/\arty
This is the end of the thread.
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