![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 30 to 54 of 70. Go back in thread:
Posted by not exactly on March 5, 2003, at 13:44:19
In reply to Re: Dopamine agonists, posted by Michael Bell on March 5, 2003, at 10:59:53
> Regarding upregulation - interestingly, in people with Parkinson's disease, studies have shown that as the number of dopamine cells gets lower, the brain upregulates the number of receptors to compensate. However, eventually the number of cells get so low (80% reduction) that even having a higher number of receptors doesn't help. So there is probably a way to increase the number of dopamine receptors, but safety is a big issue.
I sometimes worry about Parkinson's. I have no symptoms of the disease yet, but it concerns me that most of the meds that have dramatically helped me are in fact primarily for Parkinson's rather than depression or SP. Do I have the so-called "Parkinson personality" (the description fits like a glove, see http://www.parkinson.org/pr24.htm and http://www.geocities.com/parkinsonforum/hypothesis/overview.htm), and am I therefore at risk for an early onset of the disease itself? I wonder if drugs that are neuroprotective and reputedly slow the advance of Parkinson's, such as selegiline (low dosage), might have a long-term benefit.
The up/down regulation issue also reminds me of the triumphs and tragedies in the famous "Awakenings" story.
BTW, I responded well to Klonopin, but never tried it very long, or as a monotherapy. My pdoc switched me from Klonopin to Neurontin because he was concerned about the addiction potential of benzo's. Neurontin helped in much the same ways as Klonopin, but never as well, and with some subtle but worrisome long-tem effects. I've reported on my reaction to Neurontin in another thread [http://www.dr-bob.org/babble/20030125/msgs/137900.html].
- Bob
Posted by daizy on March 5, 2003, at 15:47:35
In reply to Re: Dopamine agonists » Michael Bell, posted by not exactly on March 5, 2003, at 13:44:19
I did a search on GABA, and found you can get capsules, Is this something totally different to the GABA we are talking about?
Posted by noa on March 5, 2003, at 16:52:43
In reply to Re: Dopamine agonists » Michael Bell, posted by not exactly on March 5, 2003, at 13:44:19
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: some possibilities, imho: poor people get less discerning health care and therefore are diagnosed way less, or diagnosed with alternative illnesses thought to be more prevalent in the poor; more economically successful people tend to live longer and are able to function in their jobs longer becuase jobs tend to be white collar, not physical labor; stress and strains and injuries from long years of labor could be mistaken for the causes of some Parkinsons symptoms, or of earlier aging, which can seem to mask P. symptoms; Drug and alcohol use can mask P. symtpoms, or get in the way of access to good health care, or prejudice health care professionals from diagnosing properly, etc. etc. etc.
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 sometimes think about Parkinsons. My grandmother essentially died of it. It was not diagnosed that readily. In fact, my dad and his siblings actually suspected my grandfather of abusing her becuase she had been falling a lot and getting bruised. He had developed a drinking problem in later years to self-medicate his depression. But abuse did not fit his m.o., in that he tended to be a quiet, withdrawn drunk, very depressed, and had more of a tendency to wander aimlessly than to have any kind of angry outbursts. After a while, they realized that my GM was falling because of something neurological and then she saw a specialist who diagnosed her. This was back in the 60's.
I don't even have a clue if P. is hereditary, but of course, I think about it from time to time.
Posted by Ed on March 5, 2003, at 16:59:43
In reply to Re: Dopamine agonists » Michael Bell, posted by not exactly on March 5, 2003, at 13:44:19
> BTW, I responded well to Klonopin, but never tried it very long, or as a monotherapy. . . . >
> - BobBob- have you tried/did you respond to, Nardil. You and I have very similar symptoms and I responded well to Nardil but couldn't bear the weight gain. I think dopamine is the culprit. --Ed
PS-- I had concluded that these symptoms we share are not so different from the negative symptoms of schizophrenia. I don't know if that has any relevance-- maybe it means nothing-- maybe there are only so many symptoms that can manifest from brain dysregulation, and entirely different problems can manifest entirely similar symptomology.
>
>
Posted by not exactly on March 5, 2003, at 18:18:54
In reply to Re: Dopamine agonists » not exactly, posted by Ed on March 5, 2003, at 16:59:43
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
Posted by zeugma on March 5, 2003, at 20:19:09
In reply to Re: Dopamine agonists, posted by Michael Bell on March 4, 2003, at 23:01:38
This is a very interesting discussion. I definitely have Social Phobia, but I have only become aware of it as a result of taking an AD for depression and overall dysfunction and malaise. The fear I used to feel was too constant to put a finger on what was causing it and why. Now I am aware that I am terribly uncomfortable interacting with others, and I mentally try to prepare myself, while waiting for the elevator, for the dreaded possibility that there might actually be someone in that elevator with whom I might have to interact. At least now I can try to prepare myself, but it's exhausting and extremely demoralizing when my preparations fail, which is often.
I used to drink alcohol to deal with this, and it worked but took a toll on my body. I basically dropped out of graduate school for a couple of years because I found I couldn't write papers without getting very drunk in the process. I suppose writing for me is too much of an
'interaction.' Also I have noticed a kind of 'cognitive stiffness' that alcohol, in particular, seemed to remedy. People said I seemed much more natural and normal when drunk than when sober. I do know that something happens in my brain when I drink that magnifies my problem-solving and creative capacities, and helps me pass for 'normal.' GABA release and dopamine transmission sound like likely reasons for this, especially the dopamine transmission. Dopamine governs movement, right? A lot of times I feel that life is a series of incredibly complicated movements, and I can only manage a few at a time until I trip myself up. It's that 'fluidity' that I value so much in alcohol. I'm wondering if I should think about taking Nardil. Right now I'm on 40 mg nortriptyline and 30 mg Buspar. I'm thinking I should push the dosages of these meds as much as possible- they've both helped a lot but have also made me aware of how far I still have to go. If I didn't practically live on soy products, curiousity, as well as a desire to solve these long-standing problems, would have asking for Nardil next time I see my doc.
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
Go forward in thread:
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.