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Posted by Stan on March 6, 2003, at 1:37:19
In reply to Re: Dopamine agonists » Ed, posted by not exactly on March 5, 2003, at 18:18:54
> Ed,
>
> > have you tried/did you respond to, Nardil.
>
> Not yet, but it's high on my list of things to try if/when my current AD (Desipramine augmented w/ Buspar) proves disappointing. The only MAOI I've ever tried was the Selegiline Patch, which was very effective for me.
>
> > I had concluded that these symptoms we share are not so different from the negative symptoms of schizophrenia.
>
> Atypical antipyschotics (which I haven't tried yet either) might help also, especially in low dosage as an adjunct to an AD.
>
> - Bob>>>>>>>>>>>>>>>>>>>>>>>>>>>
hi bob -- last i heard, you were in the process of phasing out neurontin -- have you reduced that to zero now and replaced it with buspar? if so, what do you think of the change? thanks
Stan
Posted by not exactly on March 6, 2003, at 4:48:01
In reply to Re: Dopamine agonists » not exactly, posted by Stan on March 6, 2003, at 1:37:19
> last i heard, you were in the process of phasing out neurontin -- have you reduced that to zero now and replaced it with buspar? if so, what do you think of the change?
Stan,
It's only been a week since I started the Buspar, and the effect is still ramping up. I'm going to wait until the Buspar benefits plateau out before trying to wean myself off the Neurontin completely. Being a scientist at heart, I like to control my variables - change only one thing at a time. Otherwise, I won't know what med change is responsible for what symptom change. Of course, there are so many subtle variables that I can't control (or even be aware of) so I may never really be sure. For now, the Buspar is helping with anxiety, but it's too soon to tell if it will provide the same benefits that Neurontin has.
- Bob
Posted by Michael Bell on March 6, 2003, at 12:24:45
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 5, 2003, at 7:47:36
> >
> > So to sum it up, it seems to me that GABA dysfunction is the main reason for SP, with poor dopamine transmission due to chronically excess levels in brain as a result of low GABA"
>
>
> So does this mean that to combat SP and anxiety, you need a drug that primarily increases GABA, and then adding an SSRI or SNRI to increase the levels of others?
>
> I think I have understood!
>
Since Klonopin and a few others seem to be very effective for SP with little or no direct effect on serotonin or norepinephrine, I guess what I was saying is people with SP need to attack the GABA system primarily, then add a little something to increase Dopamine transmission.
>
Posted by Michael Bell on March 6, 2003, at 12:35:26
In reply to Re: Dopamine agonists » Michael Bell, posted by jumpy on March 5, 2003, at 11:38:17
>
> Hey Michael,
>
> Very interesting. So with nardil, is the benefits solely in the increase in GABA levels and the increases in dopamine/serotonin/norepi are actually detrimental? I am on nardil and klonopin ... should I just taper off the nardil and increase the klonopin if increasing GABA is the sole goal (and nardil might be hurting with the serotonin/dopamine/norepi effects)?
>
> Thanks.
>
> JumpyJumpy, I think the creators of Nardil "stumbled" on a highly effective med for Social Phobia when they came up with Nardil. I'm not sure of the exact date, but Nardil has been around for at least a couple decades. Social Phobia wasn't even recognized as a separate illness until very recently, long after Nardil was on the market. What probably happened (and I'm guessing here" is that it was intended primarily as an antidepressant, but over the years they started getting reports that it worked really well for agoraphobia/SP. So now its marketed as a SP med as well. I don't know if the effects on DA, NE and SE are detrimental, but I'm positive that GABA is the reason for its supreme effectiveness. Parnate, Selegiline (high doses), Moclobemide, etc. don't work nearly as well for SP.
Also, I wouldn't want to recommend any changes in your med cocktail. I'm just working on theory here, with no medical background. Try and figure out how you felt with each med, and the effects that adding them to your regimen had. Then talk to your psych and see what he thinks. Good luck!
Posted by not exactly on March 6, 2003, at 15:02:04
In reply to Re: Dopamine agonists (daizy), posted by Michael Bell on March 6, 2003, at 12:24:45
> ... people with SP need to attack the GABA system primarily, then add a little something to increase Dopamine transmission.
This sounds like a good plan, but what do you think that "little something" should be? What med (or class of meds) might have a long-term beneficial effect on Dopamine transmission? I would think that anything which increases the amount of DA present (or otherwise stimulates DA receptors, such as a direct DA agonist) runs the risk of eventual dowregulation (a.k.a. "poop-out").
- Bob
Posted by jumpy on March 6, 2003, at 16:09:14
In reply to Re: Dopamine agonists jumpy, posted by Michael Bell on March 6, 2003, at 12:35:26
Posted by daizy on March 6, 2003, at 16:34:11
In reply to Thanks a million Michael! (nm) » Michael Bell, posted by jumpy on March 6, 2003, at 16:09:14
Yes I should also say THANK YOU! ;-)
Posted by djmmm on March 6, 2003, at 17:56:47
In reply to Re: Dopamine agonists (daizy) » Michael Bell, posted by not exactly on March 6, 2003, at 15:02:04
Nardil, Zonegran and GHB are the only meds that I know of that specifically target GABA and Dopamine...
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8991786&dopt=Abstract
Posted by Ilene on March 9, 2003, at 21:28:29
In reply to Re: Dopamine agonists, posted by Michael Bell on March 3, 2003, at 19:26:29
> Daizy, an agonist potentiates increases dopamine/effects of dopamine, whereas antagonist would inhibit dopamine. In my situation, and in most situations I've read about (this board included), drugs that primarily increase dopamine (or effectiveness of dopamine) make anxiety symptoms worse in people with SP. The reason I'm trying to get an idea of the effectiveneness of these types of drugs on SP is because I'm convinced dopamine levels/transmission has a role in SP, but I can't put my finger on it. By the way, If you're looking to for calmness, try a drug that works on GABA, if your doc is cool with it.
>
> Also, I have a theory on neurochemical cause of Social Phobia, but it's quite long. Let me know if you want to hear it, and I'll post it. Thanks.*I'm* interested. I don't know if I have SP. I don't know if it matters; depression and inability to socialize go hand in hand for me.
I've been wondering--are there any drugs that amp up dopamine (or keep it from being taken up) that don't affect other neurotransmitters? Would Parkinson's drugs do it? If so, why aren't they prescribed more often for people w/ mood disorders? Is it because of side effects or some other deeply biochemical reason? Should I palm some Sinemet the next time I see my dad?
How much of the pleasure of "drugs of abuse" is due to dopamine? Is part of it from the adrenalin boost?
Life is *full* of mysteries.
--I.
Posted by Ilene on March 9, 2003, at 23:47:01
In reply to Re: Parkinsons, posted by noa on March 5, 2003, at 16:52:43
> The second site you linked is very interesting! I like the way the info is organized, too.
>
> But when I read the first link, I was somewhat skeptical of a Parkinsons personality, because there, it is described as:
>
> "...appear to be highly intelligent, successful, responsible, conscientious, hard-working, less likely to smoke or drink, law abiding individuals."
>
> Obviously, this is too broad to be useful. And,possibly spurious. One could easily imagine several ways that one could get the impression that patients diagnosed with Parkinsons have these traits vs. their opposites:
>
> The second link talks more about compulsive tendencies. I will have to go back and look at the research they based this on, but that sounds more promising to me than the above characteristics.
>I wonder how useful it is to evaluate personality *after* someone has been diagnosed, and I wonder if the disease affects personality long before other symptoms become apparent. Or is it supposed to be the other way around? Uptight folks get Parkinson's? Assuming it affects personality at all. There are a zillion hard-working, conscientious, non-smokers who *don't* get Parkinson's.
> I sometimes think about Parkinsons. My grandmother essentially died of it. It was not diagnosed that readily.
>
> I don't even have a clue if P. is hereditary, but of course, I think about it from time to time.Supposed to be *not* hereditary. My dad has it.
--I.
Posted by not exactly on March 12, 2003, at 5:51:20
In reply to Re: Dopamine agonists (daizy) » Michael Bell, posted by not exactly on March 6, 2003, at 15:02:04
> ... people with SP need to attack the GABA system primarily, then add a little something to increase Dopamine transmission.
Well, I've tried to apply what I've learned from following this thread, and I'm happy to report some dramatic success. I'm now on Klonopin plus Buspar, and I'm finally experiencing virtually complete remission from my long-standing Social Phobia and comorbid treatment-resistant Atypical Depression (anhedonia, mood reactivity, hypersomnia).
Previously, I had been on Desipramine plus Neurontin. After giving the Desipramine a fair trial (5 weeks) and obtaining only slight relief from my depression, I augmented it with Buspar. This yielded a modest improvement, but overall it was still an unsatisfying solution.
Inspired by the enlightening posts in this thread, I decided to make some radical changes. First, I dumped the Neurontin and substituted Klonopin. This gave improved relief from SP and GAD, and eliminated the "dulled" feeling that Neurontin had produced. I then dropped the Desipramine (but kept the "augmenting" Buspar). Wow. Within a few days, I felt much more upbeat, motivated, and "present". This is one of the best states I've ever been in. Not manic, just functional and happy to be alive. And NO SIDE EFFECTS.
I've noticed some amazing changes. Earlier this evening, I attended a meeting with some friends, and there were 3 new members in the group. I had enjoyable conversations with all 3 of them, and I remember their names. Maybe this doesn't seem unusual to you, but it's a BIG change for me. It used to be that the presence of "strangers" would make me so uncomfortable that I wouldn't say anything at all, even to my old friends. It would take me weeks to warm up to new acquaintances enough to make relaxed conversation possible. And months before I had a chance of remembering their names.
I've been feeling this good for several days. I sure hope this state is sustainable. Don't know if this combo would work this well for anyone else, but it's been a miracle cure for me.
- Bob
Posted by Krissy P on March 12, 2003, at 8:59:21
In reply to SUCCESS!, posted by not exactly on March 12, 2003, at 5:51:20
Posted by daizy on March 12, 2003, at 9:04:45
In reply to SUCCESS!, posted by not exactly on March 12, 2003, at 5:51:20
> > ... people with SP need to attack the GABA system primarily, then add a little something to increase Dopamine transmission.
>
> Well, I've tried to apply what I've learned from following this thread, and I'm happy to report some dramatic success. I'm now on Klonopin plus Buspar, and I'm finally experiencing virtually complete remission from my long-standing Social Phobia and comorbid treatment-resistant Atypical Depression (anhedonia, mood reactivity, hypersomnia).
>
> Previously, I had been on Desipramine plus Neurontin. After giving the Desipramine a fair trial (5 weeks) and obtaining only slight relief from my depression, I augmented it with Buspar. This yielded a modest improvement, but overall it was still an unsatisfying solution.
>
> Inspired by the enlightening posts in this thread, I decided to make some radical changes. First, I dumped the Neurontin and substituted Klonopin. This gave improved relief from SP and GAD, and eliminated the "dulled" feeling that Neurontin had produced. I then dropped the Desipramine (but kept the "augmenting" Buspar). Wow. Within a few days, I felt much more upbeat, motivated, and "present". This is one of the best states I've ever been in. Not manic, just functional and happy to be alive. And NO SIDE EFFECTS.
>
> I've noticed some amazing changes. Earlier this evening, I attended a meeting with some friends, and there were 3 new members in the group. I had enjoyable conversations with all 3 of them, and I remember their names. Maybe this doesn't seem unusual to you, but it's a BIG change for me. It used to be that the presence of "strangers" would make me so uncomfortable that I wouldn't say anything at all, even to my old friends. It would take me weeks to warm up to new acquaintances enough to make relaxed conversation possible. And months before I had a chance of remembering their names.
>
> I've been feeling this good for several days. I sure hope this state is sustainable. Don't know if this combo would work this well for anyone else, but it's been a miracle cure for me.
>
> - Bob
>WOW! this is great news. I think Michael's come up with a great theory, with proof it works! I had heard Buspar was good for anxiety. And no side effects you say?... May I ask did you do this with the advise of your doctor? How long has it taken for the effects to kick in? Good Luck........ Daizy
Posted by Ed on March 12, 2003, at 9:36:17
In reply to SUCCESS!, posted by not exactly on March 12, 2003, at 5:51:20
Bob- do you think the Klonopin and the Buspar create a synergistic effect for you? Or do you think each addresses a different symptom cluster?
Posted by Ilene on March 12, 2003, at 9:59:06
In reply to SUCCESS!, posted by not exactly on March 12, 2003, at 5:51:20
>
> Well, I've tried to apply what I've learned from following this thread, and I'm happy to report some dramatic success. I'm now on Klonopin plus Buspar, and I'm finally experiencing virtually complete remission from my long-standing Social Phobia and comorbid treatment-resistant Atypical Depression (anhedonia, mood reactivity, hypersomnia).
>
>
> I've been feeling this good for several days. I sure hope this state is sustainable. Don't know if this combo would work this well for anyone else, but it's been a miracle cure for me.
>
> - Bob
>I wonder if there is a way to compile the experiences of PBers to correlate symptions/diagnosis with meds that work or don't work.
It would be so valuable to people who are constantly experimenting with all the possible med combinations.
I've read papers that claim X kind of med works best for Y condition, but I don't know rigorous they are. It seems so *obvious* that someone *must* have done it. Although I can see the difficulties,
My database mind is ticking away.
--I.
Posted by not exactly on March 12, 2003, at 19:22:15
In reply to Re: SUCCESS!, posted by daizy on March 12, 2003, at 9:04:45
> WOW! this is great news. I think Michael's come up with a great theory, with proof it works!
If a single datapoint can be considered "proof". YMMV, but I'm a believer now!
> I had heard Buspar was good for anxiety.
Of course, that's its only approved use. The big surprise to me was that it was such an effective antidepressant, at least for my kind of depression.
> And no side effects you say?
None of any significance. Occasional very slight headache, but it's hard to say if it is "caused" by the meds. The wonderful thing is that I don't feel like I'm on medication at all.
> May I ask did you do this with the advise of your doctor?
Yes and no. The meds I'm now taking are current prescriptions from him at the recommended dosages. The choice to stop taking the other 2 prescribed meds was unilateral. He's on vacation now, and I plan to discuss this with him when he returns. In the past, he's never expressed any concern about my choices to discontinue meds when I became convinced that they weren't helping. He knows that I do careful reasearch, understand the chemical/medical implications, and wouldn't do anything rash.
> How long has it taken for the effects to kick in?
The beneficial effects that I'm attributing to the Buspar took about a week to fully manifest. For the first few days, it made me drowsy, foggy, and anxious, but after a while, the effects became just the reverse - I'm now feeling energized, alert, and unstressed.
The Klonopin kicked in almost immediately. The initial sedation disappeared after a day or 2, leaving me feeling self-confident instead of hypersensitive. An instant cure for SP.
Of course, we don't know what (if any) effect the other (now discontinued) meds may have had on the timing or overall result.
- Bob
Posted by not exactly on March 12, 2003, at 19:28:09
In reply to Re: SUCCESS! » not exactly, posted by Ed on March 12, 2003, at 9:36:17
> do you think the Klonopin and the Buspar create a synergistic effect for you? Or do you think each addresses a different symptom cluster?
Hard to say. I'm convinced of the latter, but can't rule out synergy. I've never tried either med as a monotherapy, and I'm not about to try the controlled experiment of discontinuing either of them now.
- Bob
Posted by Ron Hill on March 13, 2003, at 2:57:23
In reply to SUCCESS!, posted by not exactly on March 12, 2003, at 5:51:20
Bob,
Thanks for posting your initial success with Klonopin and Buspar. Because of your post I added Buspar to my list of meds to investigate if my current cocktail poops out.
Thanks, and please keep us informed as to how this trial unfolds.
-- Ron
Posted by not exactly on March 13, 2003, at 4:47:36
In reply to Is the above Dr. BOB?????? (nm), posted by Krissy P on March 12, 2003, at 8:59:21
Posted by not exactly on March 13, 2003, at 5:20:27
In reply to Re: SUCCESS! » not exactly, posted by Ilene on March 12, 2003, at 9:59:06
> I wonder if there is a way to compile the experiences of PBers to correlate symptions/diagnosis with meds that work or don't work.
There are some broad generalities that yield useful guidelines for starting points [e.g. http://www.biopsychiatry.com/depressiontypes.htm] but people's reactions to meds are so ideosyncratic that a simplistic "Rx for every Dx" is unfortunately not possible. If you actually attempted to compile the sort of database you suggest, you'd find so much contradictory evidence that the information would be virtually useless. The most promising approach may be the "flowchart" model [e.g. http://www.mhc.com/Algorithms/Depression/flowchar.htm].
- Bob
Posted by not exactly on March 13, 2003, at 6:24:52
In reply to Re: SUCCESS! » not exactly, posted by Ron Hill on March 13, 2003, at 2:57:23
> I added Buspar to my list of meds to investigate if my current cocktail poops out.
I'm curious - what is your current successful cocktail, and what symptoms does it address?
> please keep us informed as to how this trial unfolds.
Will do.
- Bob
Posted by Ilene on March 13, 2003, at 9:27:35
In reply to Re: SUCCESS! » Ilene, posted by not exactly on March 13, 2003, at 5:20:27
> > I wonder if there is a way to compile the experiences of PBers to correlate symptions/diagnosis with meds that work or don't work.
>
> There are some broad generalities that yield useful guidelines for starting points [e.g. http://www.biopsychiatry.com/depressiontypes.htm] but people's reactions to meds are so ideosyncratic that a simplistic "Rx for every Dx" is unfortunately not possible. If you actually attempted to compile the sort of database you suggest, you'd find so much contradictory evidence that the information would be virtually useless. The most promising approach may be the "flowchart" model [e.g. http://www.mhc.com/Algorithms/Depression/flowchar.htm].
>
> - Bob
>As I said, there would be difficulties...I'm just noodling around. To do it right would be beyond the capacity of a mere mortal. But it's an interesting source of raw data.
(I constructed a little database as a class project that tried to match patients to clinical trials. My biggest problem was the translation of natural language into yes/no criteria. I also discovered that people who were doing this kind of thing at NIH and elsewhere were doing it *wrong*.)
The algorithms aren't much help when you've gone through 5 or 6 drug trials and combinations. Some of the recommendations seem like they are based on a show of hands. When you get all excited about a trial of chromium picolinate using 15 people, something is awry.
There's a real difference between physicians who work with patients and those who design research studies. I was astonished when I read that evidence-based medicine was controversial. (That was a few years ago. Maybe it's different now.) What is the practice of medicine supposed to be based on? The Tarot?
When you see your friendly neighborhood psychiatrist, s/he usually bases decisions on personal experience. The "art" of medicine. It's hard to discern patterns when you're not getting a statistically valid sample.
I'm starting to rant. I'd better stop before I feel the need to provide footnotes.
--I.
Posted by jflange on March 13, 2003, at 18:37:29
In reply to SUCCESS!, posted by not exactly on March 12, 2003, at 5:51:20
not exactly:
I am really excited to hear of your success, especially since I too have experienced such a huge remission of social phobic responses since adding Buspar that sometimes I also surprise myself. I too attribute it to B's influence on dopamine but I do not have a real answer for the whys or hows of its mechanism.
You might remember that I take B with Zoloft for their combined dopaminergic and serotonergic effects, but I have been thinking lately that I really do not need the Zoloft (or not as much as I take), since it seems to feel at times like speed.
So I am FASCINATED to hear of your success with Klonopin. K has been in the back of my mind, and I would LOVE to hear you say exactly what you think is going on with this drug combo to make it work for you. I know a good drug combo sometimes feels like magic dust that you'd rather not analyze, but since you say you are a (lay?) med researcher, I would like to hear what your hypothesis is.
congrats!
jflange
Posted by not exactly on March 13, 2003, at 23:48:14
In reply to Re: SUCCESS with K and Buspar, posted by jflange on March 13, 2003, at 18:37:29
> I would LOVE to hear you say exactly what you think is going on with this drug combo to make it work for you. I know a good drug combo sometimes feels like magic dust that you'd rather not analyze, but since you say you are a (lay?) med researcher, I would like to hear what your hypothesis is.
Generally, I'm attributing the SP relief to the Klonopin (GABA transmission enhancement), and the antidepressant action to the Buspar (5-HT1A & D2 effects). But it's also possible that the Klonopin is helping with the depression and the Buspar is helping with the SP. As I've mentioned earlier, I've never tried either of these drugs by themselves, so I'm not sure which one is doing exactly what, or how significant the synergy might be.
I got most of my information /theories on SP/GABA/Klonopin from Michael Bell's previous posts to this thread:
http://www.dr-bob.org/babble/20030301/msgs/206003.html
http://www.dr-bob.org/babble/20030306/msgs/206478.htmlI got most of my information /theories on Buspar from other Psycho-Babble threads:
http://www.dr-bob.org/babble/20010522/msgs/63954.html
http://www.dr-bob.org/babble/20000112/msgs/19512.htmlThe most encouraging part is that the improvement came on slowly, which makes me believe that it was a secondary effect of accomodation/downregulation. In my experience, instant good results tend to fade as my body chemistry manages to compensate for the temporary "imbalance". My hope is that the compensation has already taken place, producing the benefits rather than cancelling them out.
- Bob
Posted by Geoffrey Ruch on April 12, 2004, at 1:39:26
In reply to Re: Dopamine agonists, posted by Michael Bell on March 4, 2003, at 23:01:38
Michael,
I have not read any of the responses to your message, but I have a few questions eating at me and I was hoping you might be able to help me understand.
First of all, I read on the internet, on a site written by a doctor specializing in Social Phobia and Avoidant Personality Disorder, that Parnate is superior to Nardil in treating these disorders. So I'm confused by your assertion that Nardil is superior. Can you tell me where you got this information from. I just started on Parnate a few weeks ago and I'm curious as to why I'm hearing conflicting information.
Next, and most puzzling to me is in regards to Norepinephrine. I am aware that it acts both as a neurotransmitter (in the brain) as well as a hormone from the adrenal cortex. Now, many hypotheses about the cause of depression relate to the belief that Norepinephrine levels are low in the brains of depressives, and thus increasing levels of this neurotransmitter could help in the treatment of depression. Obviously there are numerous drugs out, including Tricyclics, MAO inhibitors, and newer drugs like Effexor, etc. that do just that. Additionally, naturopathic doctors recommend such supplements like the amino acid precursors L-Tyrosine and Phenylalanine (in part) because they can increase Norepinephrine levels in the brain (as well as Dopamine levels). And I've even read that L-Tyrosine has anti-stress qualities (ie. helping people cope with stress). For instance, in a book called "Prescription for Nutritional Healing," Tyrosine is at the top of the list of recommended supplements to deal with stress.
Now with all this said, Norepinephrine as a hormone is involved in the "fight or flight" stress response, and it seems, therefore, that it would increase stress and not HELP with dealing with it; and it would seem that this would impact negatively on depression (ie. increased stress can cause depression). So I'm incredibly confused! I mean, what's the deal? Is Norepinephrine, as a neurotransmitter, a completely different substance from the hormone? Or are some people with depression lacking in this hormone in addition to the neurotransmitter?
If you-- or anybody else-- could help me understand this (or direct me to where I could find help in understanding it) I would be GREATLY appreciative!!! I mean, if a depressed person under constant inner stress could benefit from increased levels of the NE neurotransmitter but be negatively impacted because of higher NE hormone levels, then what is one to do in such a case??? I'm sure the situation is very complex and it's not as simple as I have laid it out to be. Still, though, there has to be some kind of way to understand it. It's a shame I never asked my psychiatrist to explain it. Now I see a county doctor (in L.A.) who I see for about 20 minutes a session every month and a half, and I really haven't had the time to ask for an explanation.
Anyway, thank you all for allowing me into this discussion!!! I hope it is not too "off-topic." But I think it is relevant nevertheless.
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