![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 41. This is the beginning of the thread.
Posted by andys on September 16, 2001, at 12:51:57
I had some questions on dopamine therapy:
1-I have had a remarkable response (both anti-depressant and mood stabilization) to the dopaminergic drugs phentermine and mirapex, but can’t tolerate the side effects (which is common for me, on any psych meds). As an alternative to prescription meds, has anyone had experience with the supplement NADH (coenzyme #1), which is supposed to raise dopamine levels?
2- I’d like to switch from seroquel (a dopamine antagonist) to amilsupride (a dopamine agonist), but my pdoc favors ziprasidone for a switch (I use seroquel for sleep, and mood stabilizer, I am untra-rapid-cycling bipolar). I found a chart that the two have equivalent D2 agonist action, but no mention of D3. Also, is amisulpride supposed to help sleep?
3-He also claims that mirapex is primarily a serotonin 5ht agonist, and dopamine is secondary, which I can find no research to support his supposition, any thoughts? (I need to resolve, to support my argument that it’s dopamine I respond to, and need to pursue in the future).
4-A Parkinson’s site says that although D2 helps the Parkinson’s symptoms, it’s the D3 that is responsible for the anti-depressant and mood elevating properties, and therefore, I should focus mostly on the D3 agonist drugs. Any thoughts on this, and which drugs have the most potent D3 agonist? By the way, there’s an interesting chart on dopamine agonists of different drugs at:
http://www.psychiatry-in-practice.com/html/resources/volume1gerlach.aspThanks,
Andy
Posted by Zo on September 16, 2001, at 17:10:04
In reply to dopamine drugs or supplements, posted by andys on September 16, 2001, at 12:51:57
What kind of side effects?
And, have you tried any just plain stimulants, Dexedrine or Adderall. . .
Or Weebutrin, to my knowledge the most dopaminergic (maybe the only) AD.
Zo
Posted by Grouch on September 16, 2001, at 22:38:45
In reply to dopamine drugs or supplements, posted by andys on September 16, 2001, at 12:51:57
> 2- I’d like to switch from seroquel (a dopamine antagonist) to amilsupride (a dopamine agonist),Hi Andy. Amisulpride is actually a D2/D3 antagonist (not agonist), but it works differently than seroquel and ziprasidone. While the latter block postsynaptic receptors, low doses of amisulpride block the presynaptic D2/D3 receptors which causes an increase of dopamine in the synapse. The generally results in an antidepressant effect (perhaps comparable to what you experience with Mirapex) rather than an antipsychotic or tranquilizing effect.
At high doses, amisulpride blocks post-synaptic D2/D3 receptors which results in an antipsychotic or tranquilizing effect (perhaps comparable to what you expereience with Seroquel).
>I found a chart that the two have equivalent D2 agonist action, but no mention of D3.
Interesting chart, though again, it is comparing the D2 antagonist (not agonist) actions of the different drugs.
> Also, is amisulpride supposed to help sleep?
Not usually at the low doses you would want to use it at.
> 3-He also claims that mirapex is primarily a serotonin 5ht agonist, and dopamine is secondary, which I can find no research to support his supposition, any thoughts?
I have never heard anything about Mirapex directly affecting 5HT. I would ask him where he got this information!
>(I need to resolve, to support my argument that it’s dopamine I respond to, and need to pursue in the future).
Yes, too many psychiatrists seem to think all depression revolves around serotonin. But my own experience, and what I've read from others on this board suggests that in many cases dopamine plays a critical role. Good luck.
Posted by Zo on September 16, 2001, at 22:50:09
In reply to Re: dopamine drugs or supplements » andys, posted by Grouch on September 16, 2001, at 22:38:45
> Yes, too many psychiatrists seem to think all depression revolves around serotonin. But my own experience, and what I've read from others on this board suggests that in many cases dopamine plays a critical role. Good luck.
The thing is, this wasn't the case until Prozac came out, hit the big time, and all the drug companies got on the serotonin bandwagon, and drummed into all the poor pdocs' brains. It's pretty much a story of Follow The Money. . which is rather sad.
Zo
Posted by ChrisK on September 17, 2001, at 4:29:38
In reply to dopamine drugs or supplements, posted by andys on September 16, 2001, at 12:51:57
Don't even think about Ziprasidone if it's sleep you want. I tried to switch from Zyprexa and gave it several months before giving up because I couldn't sleep anymore. Others have also written that it was too activating for them and caused manic episodes or increased anxiety.
I'm not much for the technical hows and whys things work but Mirapex was the final med in my long running battle with depression. It has been great for my anhedonia and I wouldn't give it up for anything.
Good Luck,
Chris
>
> 2- I’d like to switch from seroquel (a dopamine antagonist) to amilsupride (a dopamine agonist), but my pdoc favors ziprasidone for a switch (I use seroquel for sleep, and mood stabilizer, I am untra-rapid-cycling bipolar). I found a chart that the two have equivalent D2 agonist action, but no mention of D3. Also, is amisulpride supposed to help sleep?
>
Posted by Peter S. on September 17, 2001, at 12:12:18
In reply to Re: dopamine drugs or supplements, posted by ChrisK on September 17, 2001, at 4:29:38
After many, many, many med trials over many years, I've been on Mirapex for a couple of months plus Prozac. Prozac pooped out before, but the Mirapex really seems to help with my energy and possibly synergistically with the Prozac.
The jury is still out because I've been disapointed before, but so far I've been very impressed!
Peter
> Don't even think about Ziprasidone if it's sleep you want. I tried to switch from Zyprexa and gave it several months before giving up because I couldn't sleep anymore. Others have also written that it was too activating for them and caused manic episodes or increased anxiety.
>
> I'm not much for the technical hows and whys things work but Mirapex was the final med in my long running battle with depression. It has been great for my anhedonia and I wouldn't give it up for anything.
>
> Good Luck,
> Chris
> >
> > 2- I’d like to switch from seroquel (a dopamine antagonist) to amilsupride (a dopamine agonist), but my pdoc favors ziprasidone for a switch (I use seroquel for sleep, and mood stabilizer, I am untra-rapid-cycling bipolar). I found a chart that the two have equivalent D2 agonist action, but no mention of D3. Also, is amisulpride supposed to help sleep?
> >
Posted by andys on September 17, 2001, at 15:39:18
In reply to Re: dopamine drugs or supplements, posted by ChrisK on September 17, 2001, at 4:29:38
Thanks for all your help, and I thought it more organized to answer all (Zoe, Grouch, Peter, Chris) at once:
FIRST, THE FACTS:
I’m age 56, an ultra-rapid-cycling bipolar (up to 6 switches a day), symptoms for 15 years, unresponsive to drugs, and hyper-sensitive to side-effects. I now tolerate a low dose, and get some benefit from: 100 mg. Lamictal, .25 mg. Cytomel, .125 mg. Mirapex, 15 mg. Dexedrine, 75 mg. Seroquel (for sleep, and mood stabilizer), 1 mg. Klonopin (for sleep, and anxiety, works great). I don’t tolerate anti-depressants (when they work, they send me ballistic hypomanic).I’ve had two AMAZING (but paradoxical) experiences on dopaminergic drugs (both of them greatly stabilized my mood, both as an antidepressant, and to lessen hypomania and anxiety). I call this paradoxical, because most psychiatrists tell bipolars not to take dopamine drugs, as they’ll trigger mania. And yet, even with my inability to tolerate antidepressants due to triggered mania, the dopamine drugs work great). So here I sit, knowing that dopamine holds the key, but unable to tolerate these drugs. I’m hoping that the solution lies with combination therapy:
Phentermine: Twice, last year, I had this remarkable response from phentermine (a stimulant, somewhat-related to dexedrine), but only at very high dose. You’d expect me to be really wired at those dosages, but within 48 hours of starting the drug, I became calm, balanced, and in the best mood in 15 years. But by day 5, the insomnia became so severe, I had to quit (also, high blood pressure). I got no response at lower dose.
Mirapex:
Just last month, at .250 mg., I was so sedated and lethargic, I couldn’t take care of myself (cook, shower, etc.), and the side effects became worse over time. But 48 hours after quitting Mirapex, I got this same magical response as above, which faded after a week of being off the mirapex. (The theory being that the blood level of mirapex reduced immediately, removing the side effects, and letting the benefits show through, then the brain-level concentration diminished over the next week, as the benefits slowly went away). A new trial at the lower .125 mg. Gave me the same paralyzing lethargy, without any benefit, when I went off.
ZO’S COMMENT ON SEROTONIN OBSESSION:
I read an article on reboxetine, the first noradrenaline drug (NARI), which put some perspective on things, with the comment that serotonin isn’t necessarily the most important neurotransmitter for depression, it’s just the first one that they’ve developed the technology to successfully manipulate for depression. Which leaves it to intelligent (and usually desperate) people like in this newsgroup to be pioneers in alternate therapies.AMISULPRIDE
Grouch, thanks for clearing up the amisulpride pre-synaptic/post-synaptic, agonist/antagonist quagmire I’ve been wallowing in. Let’s see if I got it right. My understanding is that amisulpride would work synergistically with Mirapex, in that the amisulpride’s antagonism would block pre-synaptic dopamine (is this technically similar to a re-uptake inhibitor?). This would then leave more dopamine available for synapse. Then Mirapex’s post-synapse increase in D2/D3 leaves more dopamine available for the next synapse firing, so you use the two drugs to increase dopamine at both ends of the synapse.
Also, do you have any technical references on amisulpride benefits (say, as compared to ziprasidone, which my pdoc is big on), to justify him allowing me to switch?SEROQUEL
First, is seroquel a dopamine antagonist, and therefore counter-productive? And if so, any ideas on sleep meds? In anticipation of the possibility that amisulpride might not have the sleep benefits, I backed off on my seroquel from 75 mg. To 25 mg. For 3 nights, just to see if I could live without it (just slept on 5 mg. Klonopin), and it was hell. I’m concerned that my seroquel (or the Zyprexa I was previously on) is counter-productive, in that they’re dopamine antagonists. but I need something for sleep (hopefully, eventually, a successful dopamine therapy would handle sleep too, but I need something in the meantime. I’ve tried all the usual (ambien, halcyon quit after 5 days, and I don’t tolerate the anti-depressants).ANY COMMENTS ON MY STRATEGY TO USE COMBINATION THERAPY TO USE LOW-DOSE MIRAPEX (TO TOLERATE SIDE EFFECTS), AUGMENTED BY OTHER DOPAMINERGIC DRUGS?:
1-Switch from Dexedrine to Modafinil, as it is more dopaminergic, than just a CNS stimulant (anyone have references to modafinil’s dopamine benefits over Dexedrine?)
2-Try to tolerate higher dose lamictal, since I read several comments about it being a dopamine reuptake inhibitor. (any references to this?)
3-Add amisulpride (only if I can find a substitute for seroquel for sleep).
4-Add the supplement NADH (still up for debate), that’s supposed to raise dopamine levels.
Posted by SalArmy4me on September 17, 2001, at 16:07:35
In reply to Re: andy's answer to all, posted by andys on September 17, 2001, at 15:39:18
Modafinil does not work on dopamine at all: http://www.rxlist.com/cgi/generic2/modafinil_cp.htm It is useless in depression unless one has trouble with drowsiness.
I wonder if you have tried Neurontin or not.
Posted by Jane D on September 17, 2001, at 17:18:07
In reply to Re: andy's answer to all » andys, posted by SalArmy4me on September 17, 2001, at 16:07:35
> Modafinil does not work on dopamine at all: http://www.rxlist.com/cgi/generic2/modafinil_cp.htm It is useless in depression unless one has trouble with drowsiness.
Sal,
Could you elaborate. Do you mean Modafinil was useless for you? That it is useless for most people? That it has not been studied yet for this indication? I'm sure you don't mean that it will not work for anyone since that is something you can't possibly know.I looked at the web site you referred to and I wasn't sure that it really said this didn't affect dopamine at all. Also, while it was very interesting to read, I didn't see any author's name on that entry. I admit I didn't search the entire site. Do you know where I could find that information?
Finally I do know of one reference to Modafinil and depression. Check out
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10847314&dopt=Abstract
for a description of Modafinil as an augmenter. Personally, I don't take a case series of 7 all that seriously but you have listed similar articles many times in the past so I assume that you do think that these reports are important.
-Jane
Posted by Grouch on September 17, 2001, at 21:53:43
In reply to Re: andy's answer to all, posted by andys on September 17, 2001, at 15:39:18
> FIRST, THE FACTS:
>[...] I don’t tolerate anti-depressants (when they work, they send me ballistic hypomanic).May I ask which specific antidepressants?
> I’ve had two AMAZING (but paradoxical) experiences on dopaminergic drugs (both of them greatly stabilized my mood, both as an antidepressant, and to lessen hypomania and anxiety). I call this paradoxical, because most psychiatrists tell bipolars not to take dopamine drugs, as they’ll trigger mania.In addition you mentioned that you take dexedrine which is pro-dopaminergic and would tend to trigger mania. Do you mind if I ask what particular symptoms this seems to help with? Lamotrigine, though mood-stabilizing, is mildly dopaminergic as well.
> AMISULPRIDE
> [...] Let’s see if I got it right. My understanding is that amisulpride would work synergistically with Mirapex, in that the amisulpride’s antagonism would block pre-synaptic dopamine (is this technically similar to a re-uptake inhibitor?). This would then leave more dopamine available for synapse.The result is similar, the mechanism is a little different. In a dopaminergic neuron, the presynaptic D2/D3 autoreceptors form part of a feedback loop. When the neuron releases dopamine, eventually some of it comes back to the presynaptic autoreceptors which signal the neuron to stop releasing dopamine. When the presynaptic autoreceptors are blocked (as amisulpride would do)
the feedback loop is broken and more dopamine is released into the synapse. A reuptake inhibitor would keep the neurotransmitter in the synapse longer, so it would build up, but an [ideal] reuptake inhibitor doesn't stimulate neurotransmitter release.>Then Mirapex’s post-synapse increase in D2/D3 leaves more dopamine available for the next synapse firing, so you use the two drugs to increase dopamine at both ends of the synapse.
Well, in theory they could work synergistically to stimulate any post-synaptic dopamine receptors, especially D2 and D3. Just keep in mind that theory does not always hold true in practice. Also, this may be splitting hairs, but, as an agonist, Mirapex does not actually increase dopamine levels, rather it *acts* similarly to dopamine by stimulating D2 & D3 receptors.
> Also, do you have any technical references on amisulpride benefits (say, as compared to ziprasidone, which my pdoc is big on), to justify him allowing me to switch?
No comparisons to ziprasidone, but to other typical and atypical antipsychotics. The first link is the manufacturer's product monograph and has a *lot* of good information.
http://www.sanofi-synthelabo.com.ph/library/monographs/solian/index.shtml
http://www.priory.com/focus13.htm
> SEROQUEL
> First, is seroquel a dopamine antagonist,Yes. (D2)
> and therefore counter-productive?
Not necessarily. It may that you just need D3 stimulation. It is difficult to predict how they will interact in actual use.
> ANY COMMENTS ON MY STRATEGY TO USE COMBINATION THERAPY TO USE LOW-DOSE MIRAPEX (TO TOLERATE SIDE EFFECTS), AUGMENTED BY OTHER DOPAMINERGIC DRUGS?:
> 1-Switch from Dexedrine to Modafinil, as it is more dopaminergic, than just a CNS stimulant (anyone have references to modafinil’s dopamine benefits over Dexedrine?)I definitely don't think modafinil is more dopaminergic than dexedrine (as someone else also pointed out).
> 3-Add amisulpride (only if I can find a substitute for seroquel for sleep).
You could try them together, though you're stepping into uncharted territory. Mixing all these antipsychotics could increase potential for EPS or movement disorders.
Hope this helps. My brain's kind of fuzzy tonight, so I hope my explanations weren't too incoherent.
Posted by Mitch on September 17, 2001, at 23:49:57
In reply to Re: andy's answer to all, posted by andys on September 17, 2001, at 15:39:18
> FIRST, THE FACTS:
> I’m age 56, an ultra-rapid-cycling bipolar (up to 6 switches a day), symptoms for 15 years, unresponsive to drugs, and hyper-sensitive to side-effects. I now tolerate a low dose, and get some benefit from: 100 mg. Lamictal, .25 mg. Cytomel, .125 mg. Mirapex, 15 mg. Dexedrine, 75 mg. Seroquel (for sleep, and mood stabilizer), 1 mg. Klonopin (for sleep, and anxiety, works great). I don’t tolerate anti-depressants (when they work, they send me ballistic hypomanic).
>Hi, andys,
Hope you don't mind a couple of questions. I am 41 years old with BPII rapid-cycling (not ultra though), and noticed a mood stabilizing effect with Adderall (amphetamine/dextroamphetamine salts), but I got panicky with it. I am also hypersensitive to sfx, also tend to become hypomanic on AD's.
My questions are: How did the Cytomel come to be added to your drug regimen and how has it helped you (can you be detailed)??
Have you tried other psycho-stimulants besides Dexedrine and how did those affect you-for good or ill (methylphenidate, etc.)??Also, I responded better to Permax (pergolide) as a DA agonist rather than Mirapex. I had little drowsiness on the Permax (which favors D2 receptors more exclusively). The Mirapex made me much too groggy. Have you ever tried Permax??
Thanks for any info,
Mitch
Posted by andys on September 20, 2001, at 9:50:38
In reply to Re: dopamine drugs or supplements, posted by ChrisK on September 17, 2001, at 4:29:38
Again, thanks for all the great responses, here’s the answers to your questions:
RESPONSE TO GROUCH: WHICH ANTI-DEPRESSANTS TRIGGERED HYPOMANIA?
I have included other classes too, like calcium channel blockers)…
Serious hypomania: prozac, Zoloft, risperidone, SAMe (nutritional supplement),
Medium hypomania: paxil, Ritalin, tiagibine, verapimil, nimodipine, vivactil, wellbutrin, ECT (shock therapy), Neurontin (at high dose, very paradoxical).
No hypomania, but unsuccessful, due to side effects or no response:
Parnate, Nardil, effexor, buspar
Drugs that worked: desyrel (trazodone), but like mirapex, I only felt benefits AFTER I quit. I may consider Serzone, it’s supposed to be “a cleaner trazodone”. Moclobemide (helped for 6 months).GROUCH: AMISULPRIDE’S QUESTIONABLE SYNERGISM WITH MIRAPEX:
Man, you know your neurons! Sounds like I’ll skip amisulpride, too tricky. With your great input, I’m heading toward the conclusion that I should stick with a tolerable low dose of mirapex (especially for it’s D3 agonism), hoping to get synergism with my current drugs: stick with seroquel (for it’s D2 agonism, and wonderful sleep qualities), stick with Dexedrine, and raise my lamictal (which I intended to do anyway).GROUCH: DEXEDRINE SYMPTOMS:
Dexedrine gives me a mild mood lift (beyond that of just a CNS stimulant), and has pulled me out of a depression in the past. My pdoc (who is somewhat anti-dexedrine), insists it’s mood destabilizing, but it is NOT, and I get no crash from it (I tell my doc it’s an important piece of info. that I tolerate the stimulants (Dexedrine, phentermine) so well, but that antidepressants trigger mania. Someday, biopsychiatry will understand what that means). (An earlier brilliant pdoc started me on Dexedrine, to reduce coffee intake, which I agreed with him is VERY mood destabilizing for me). Although he told me Dexedrine was dopaminergic, I’ve never found anything in print.ANOTHER DOPAMINERGIC RESPONSE- THRILL SPORTS
The brilliant pdoc I mentioned above also said my mood lift from thrill sports also indicates I respond to dopamine. A true thrill sport (windsurfing, kitesurfing, skiing) gives me a BIG antidepressant hit (but very unstable, invariably transitions to hypo/anxiety, requiring klonopin). Normal exercising (bicycling, running, etc) doesn’t give this dramatic response, so it’s the thrill aspect that does it. (I offer this, in case others get this thrill response, it may be a marker for good response to dopamine).
MITCH: CYTOMEL AND STIMULANTS:
First, define rapid cycling. The PDR defines it as 4 switches a YEAR! (doesn’t seem very rapid to me). I ask, because a true rapid-cycler is considered to be a different “species”, with some different (but evolving) rules, like not treating with antidepressants, but with mood stabilizers (anti-convulsants and atypical antipsychotics). I’m not saying it’s universally true, but sure applies to me, and sounds like you need to think more in that direction too.
I ran a web site for 2 years, for ultra-rapid cycling, gathering info. on treatments that worked, and found no pattern (of any particular meds that worked). Oh, well…
The fact that we both tolerate stimulants without triggering mania is officially considered “paradoxical”, but may also be a function of rapid cyclers being a different “animal”.
Part of the evolving theory of rapid cyclers is that they are more likely to have “multiple malfunctions” going on (bipolar/endocrine/thyroid/hypoglycemia, etc), which would explain why they can be notoriously hard to treat. One theory is that rapid-cyclers may have sub-clinical thyroid disorder (or some other un-measurable thyroid disfunction). Therefore, they’re treated with thyroid meds, even if their thyroid test show normal. Thyroid is boosted with cytomel (increases T3), or synthroid (increases T4). I didn’t respond to synthroid, but get a definite activation from cytomel .25 mg.), taken with my wakeup meds (Dexedrine and lamictal). But a very successful therapy that is emerging is to take both synthroid and cytomel, to raise your overall thyroid level to the high-side of normal (even if it was originally normal). I have heard of great benefits from this, and intend to try it, after I exhaust the dopamine issues.
As far as stimulants, I’d say replace Adderall, if it makes you panicky. But my experience is limited, I tried Ritalin (didn’t like it for many reasons), and phentermine (a long explanation in my earlier message, but couldn’t tolerate, due to insomnia). Thanks for the great pergolide vs. mirapex comment, hopefully, others will add their comments too.
ANY COMMENTS ON PERGOLIDE VS. MIRAPEX?
Does anyone else have any comments on pergolide’s benefits over Mirapex? It’s definitely the sedation/lethargy side effect of Mirapex that’s in the way of getting a more dramatic response from Mirapex. I’ll go research it, but in the meantime, any comments on it’s benefits/ side effect tolerability/ preference for D3 agonism?
Posted by andys on September 20, 2001, at 10:20:47
In reply to dopamine drugs or supplements, posted by andys on September 16, 2001, at 12:51:57
I forgot to ask:
Mitch said he gets better response to pergolide, because of mirapex's sedation. My concern is that pergolide is primarily a D2 agonist, which is bad because
#1- D3 is reported to be more responsible for an antidepressant effect.
#2- since my seroquel is a D2 antagonist, it will cancel out any pergolide befefits.
Any comments?
Posted by Mitch on September 20, 2001, at 12:25:59
In reply to Re: andy's answer to all #2, posted by andys on September 20, 2001, at 9:50:38
> First, define rapid cycling. The PDR defines it as 4 switches a YEAR! (doesn’t seem very rapid to me). I ask, because a true rapid-cycler is considered to be a different “species”, with some different (but evolving) rules, like not treating with antidepressants, but with mood stabilizers (anti-convulsants and atypical antipsychotics). I’m not saying it’s universally true, but sure applies to me, and sounds like you need to think more in that direction too.
I think the DSM def. for rapid cycling is 4*plus* cycles/year. Ultra I think is cycles spanning less than 48 hrs.
Thanks for all of this info! Oh, I guess I should have been more specific. I have fairly "burned-in" chronic 3-week cycles for 25+ years now. They follow a DME pattern (depression/hypomania/euthymia). That is also coupled with seasonal major depressions twice a year.
> Part of the evolving theory of rapid cyclers is that they are more likely to have “multiple malfunctions” going on (bipolar/endocrine/thyroid/hypoglycemia, etc), which would explain why they can be notoriously hard to treat. One theory is that rapid-cyclers may have sub-clinical thyroid disorder (or some other un-measurable thyroid disfunction). Therefore, they’re treated with thyroid meds, even if their thyroid test show normal. Thyroid is boosted with cytomel (increases T3), or synthroid (increases T4). I didn’t respond to synthroid, but get a definite activation from cytomel .25 mg.), taken with my wakeup meds (Dexedrine and lamictal). But a very successful therapy that is emerging is to take both synthroid and cytomel, to raise your overall thyroid level to the high-side of normal (even if it was originally normal). I have heard of great benefits from this, and intend to try it, after I exhaust the dopamine issues.Interesting. Well, I had a thyroid tumor two years ago (during the time I had my last bout of panic attacks) and had a left thyroidectomy (it was a "cold" nodule-and it was growing FAST!). I know that T4 is used to shrink tumors.. perhaps a small dose of T4 could replace all antidepressant use for me-I would hope so, but my pdoc isn't going to play endocrinologist and my endocrinologist says he doesn't approve of it-wonderful. My Mom has epilepsy and had thyroid cancer. I had my first tumor at the same age she had her first tumor. She had her 2nd tumor 10 years later which was cancerous. So I have got to watch my half-thyroid very closely!
thanks again,
Mitch
Posted by Grouch on September 20, 2001, at 21:26:20
In reply to Re: andy's answer to all #2, posted by andys on September 20, 2001, at 9:50:38
Hi Andy. That's quite a list of ADs you've tried (mine is similarly long). Nothing really pops out at me in terms of trends or types of meds that might be helpful, though the fact that some drugs helped after quitting is interesting. Was this a brief or long-lasting response? There is a phenomenon called (I think) "withdrawal positive rebound" which I have experienced occasionally, though it generally only lasts for a few days.Good luck with raising the Lamictal... sounds like a reasonable choice.
Brief antidepressant responses to stimulants are fairly common, though it sounds like your response to Dexedrine is sustained. Excellent! Incidentally, I also find stimulants to have both calming AND anti-depressant effects simultaneously.
Regarding thrill sports - I imagine noradrenaline could also be involved with that as well as dopamine.
Don't know much about pergolide so I can't comment on that.
Posted by SLS on September 22, 2001, at 22:35:38
In reply to Re: andy's answer to all » andys, posted by SalArmy4me on September 17, 2001, at 16:07:35
> Modafinil does not work on dopamine at all: http://www.rxlist.com/cgi/generic2/modafinil_cp.htm It is useless in depression unless one has
trouble with drowsiness.
Sal.There are a few people here who have reported experiencing otherwise. Perhaps they forgot to read your citation. Some folks up at NYU must have as well. Or perhaps they all found it to be useless.
Have a nice day.
:-)
- Scott
Posted by andys on September 30, 2001, at 12:52:36
In reply to Re: andy's answer to all #2 » andys, posted by Grouch on September 20, 2001, at 21:26:20
I think I understand the phenomenon you referred to as “withdrawal positive rebound” (I figured it out myself, observing my own phenomena, for what it’s worth): When I quit a drug, the blood-level drops to the point where the side-effects go away, and the benefits (that were being masked by the side effects), show through. Because brain-levels are slower to clear out, you get the drug’s benefit for a short period, while the brain-level-concentration coasts down to a non-therapeutic level. (For me, the benefit lasts 4-5 days). Of course, if others have no side effects, my theory doesn’t hold water.
Also, for others who are very sensitive to side effects: Most pdocs will have you lower the dose, to better tolerate side effects over time, then titrate back up. I find it much more effective to completely quit the drug for 2-4 weeks. This seems to “re-set” my body, to better tolerate the drug for a second trial.
Regarding my anti-depressant response to Dexedrine, I really couldn’t characterize it as brief or sustained, since it’s just more of a “boost”, that will “nudge” me away from depression, in general. (I can “generally” say that I tend to be less depressed while on Dexedrine).
Posted by SLS on October 1, 2001, at 8:06:43
In reply to Re: grouch's rebound effect, posted by andys on September 30, 2001, at 12:52:36
> I think I understand the phenomenon you referred to as “withdrawal positive rebound” (I figured it out myself, observing my own phenomena, for what it’s worth): When I quit a drug, the blood-level drops to the point where the side-effects go away, and the benefits (that were being masked by the side effects), show through. Because brain-levels are slower to clear out, you get the drug’s benefit for a short period, while the brain-level-concentration coasts down to a non-therapeutic level. (For me, the benefit lasts 4-5 days). Of course, if others have no side effects, my theory doesn’t hold water.
> Also, for others who are very sensitive to side effects: Most pdocs will have you lower the dose, to better tolerate side effects over time, then titrate back up. I find it much more effective to completely quit the drug for 2-4 weeks. This seems to “re-set” my body, to better tolerate the drug for a second trial.
> Regarding my anti-depressant response to Dexedrine, I really couldn’t characterize it as brief or sustained, since it’s just more of a “boost”, that will “nudge” me away from depression, in general. (I can “generally” say that I tend to be less depressed while on Dexedrine).
Hi.The withdrawal rebound is most likely being produced by physiological processes in the brain that cause a shift in neural function in the direction of improvement. It might have something to do with the changes in receptor numbers or function that result from chronic exposure to the drug persisting for a few weeks after the drug is withdrawn. I am sure that it is not an illusion or unmasking due to the waning of side effects. It can be thought of as an "unspringing" of a coil spring resulting from the removal (withdrawal) of the physiological "weight" of the drug that had been compressing it. The spring ends up reaching a height greater than its initial ground state (baseline).
- Scott
Posted by andys on October 1, 2001, at 11:17:51
In reply to Re: grouch's rebound effect, posted by SLS on October 1, 2001, at 8:06:43
Scott,
To clarify my theory about feeling the benefits of a drug after it is stopped: The theory being that the benefit is actually happening, but because of serious side effects (like severe sedation), I can’t “feel” the benefit. Then when the side effect lifts (yet the brain-level of the drug is still high), I feel the benefits for 5-7 days.Can you tell me where I can read further about the “withdrawal rebound” effect? This is really important to me, because I plan on starting a painfully long trial on Mirapex, trying to overcome it’s sedation, thinking that I’ll get this wonderful response, if I ever am able to tolerate the sedation, over time. If your “unspringing” theory is true, then a long term trial isn’t necessarily going to get me the benefit I hope for, so I won’t bother with Mirapex.
-Andy
Posted by SLS on October 1, 2001, at 16:45:31
In reply to Re: Scott's rebound effect, posted by andys on October 1, 2001, at 11:17:51
> Scott,
> To clarify my theory about feeling the benefits of a drug after it is stopped: The theory being that the benefit is actually happening, but because of serious side effects (like severe sedation), I can’t “feel” the benefit. Then when the side effect lifts (yet the brain-level of the drug is still high), I feel the benefits for 5-7 days.
>
> Can you tell me where I can read further about the “withdrawal rebound” effect? This is really important to me, because I plan on starting a painfully long trial on Mirapex, trying to overcome it’s sedation, thinking that I’ll get this wonderful response, if I ever am able to tolerate the sedation, over time. If your “unspringing” theory is true, then a long term trial isn’t necessarily going to get me the benefit I hope for, so I won’t bother with Mirapex.
> -Andy
Hi Andy.At this point, I don't think it makes sense to draw any conclusions as to the effectiveness of Mirapex based upon hypotheses. If anything, there might be some predictive power behind the appearance of sedation. I don't know that there is any real evidence to substantiate that there is any, although some of us here were trying to establish an association. There may be none. However, I don't think I've seen anyone for whom sedation appeared early in treatment go on to respond well to Mirapex. Without anything definitive, though, I guess it makes sense to continue with it, especially if you have already failed to respond to many drugs.
A number of different drugs cause a rebound of one sort or another upon their discontinuation. For instance, when someone takes a benzodiazepine like Xanax or Klonopin to treat anxiety, the anxiety that appears upon the discontinuation of these drugs can be much higher than that which existed before treatment. Some sleeping pills can allow for rebound insomnia when they are discontinued. In fact, the shorter acting drugs like Halcion can produce a rebound awakening that same night as it leaves the blood stream.
If you find anything on the Internet regarding withdrawal rebound, I'd be interested to read it. Believe it or not, some people experience such a potent physiological rebound upon the discontinuation of antidepressants, that they actually become manic, even though they are not bipolar.
- Scott
Posted by Grouch on October 1, 2001, at 20:42:10
In reply to Re: grouch's rebound effect, posted by SLS on October 1, 2001, at 8:06:43
> Hi.
>
> The withdrawal rebound is most likely being produced by physiological processes in the brain that cause a shift in neural function in the direction of improvement. It might have something to do with the changes in receptor numbers or function that result from chronic exposure to the drug persisting for a few weeks after the drug is withdrawn. I am sure that it is not an illusion or unmasking due to the waning of side effects. It can be thought of as an "unspringing" of a coil spring resulting from the removal (withdrawal) of the physiological "weight" of the drug that had been compressing it. The spring ends up reaching a height greater than its initial ground state (baseline).
>
>
> - Scott
Hi Scott & Andy. I agree w/Scott on this one that improvements during withdrawal are more likely due to re-regulation of receptors rather than "brain/blood levels" or unmasking of side effects.
Posted by Zo on October 2, 2001, at 15:18:13
In reply to Re: Scott's rebound effect » andys, posted by SLS on October 1, 2001, at 16:45:31
This whole thread does bring up the interesting quanundrum (sp?) of long, painful drug trials.
And upon what basis to accept them.Zo
Posted by andys on October 2, 2001, at 18:54:36
In reply to Re: Scott's rebound effect, posted by Zo on October 2, 2001, at 15:18:13
Zo, since you brought up painful drug trials, a few thoughts:
I have done about 30-40 drug trials over the last 15 years, suffering through long periods of painful, debilitating side effects, to the point where I dread any new drug trial, and get increasingly pessimistic about being able to tolerate a therapeutic dose of anything. (Except for my precious few : klonopin, seroquel, and low-dose lamictal).It’s safe to say that I generally don’t tolerate prescription psych meds, so I have supplemented the ones I do take with nutritional supplements. I take a full array of vitamins, “just in case”. And 4 months ago, started high-dose fish oil, because a clinical trial showed it to be helpful for bipolars.
Anyway, this isn’t an introduction to a success story. I haven’t experienced any real benefits from the fish oil, but figure it is at least giving any other drugs a better chance of working.
But here’s what MAY be interesting:
I just started (and am still researching) the supplement NADH, which is supposed to raise brain dopamine, with no side effects. I’ve been on it for only 10 days, and maybe am experiencing a little benefit, but it’s too soon to say.
I emailed Dr. Birkmeyer (the “guru” of NADH, and whose father did the research of L-dopa for Parkinson’s), and did get a brief email back, although he normally doesn’t respond to emails.
He claimed that NADH was highly effective and without Mirapex’s side effects (claiming Mirapex has been taken off the market in Germany, due to it’s side effects).There’s some good info., and a pretty impressive bio of Dr. Brinkmayer at www.nadhinfo.com. But anyone that doesn’t want to baother researching it, I’m continuing the trial, and will keep you posted….
-Andy
Posted by Zo on October 3, 2001, at 15:50:38
In reply to Re: NADH for dopamine, posted by andys on October 2, 2001, at 18:54:36
Please do. Thus far, I don't know of any precursor that works. Interesting research news yesterday re: Alzheimer's and medicating the shrinking dopamne levels earlier. I'm waiting til the two uses clinically connect.. . I mean, I think they will. How can they nopt.
Zo
Posted by Zo on October 3, 2001, at 15:51:46
In reply to Re: NADH for dopamine, posted by andys on October 2, 2001, at 18:54:36
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