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Re: andy's answer to all

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:

Iím 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 donít tolerate anti-depressants (when they work, they send me ballistic hypomanic).

Iíve 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 theyíll 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. Iím 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. Youíd 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.

Just last month, at .250 mg., I was so sedated and lethargic, I couldnít 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.

I read an article on reboxetine, the first noradrenaline drug (NARI), which put some perspective on things, with the comment that serotonin isnít necessarily the most important neurotransmitter for depression, itís just the first one that theyíve 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.

Grouch, thanks for clearing up the amisulpride pre-synaptic/post-synaptic, agonist/antagonist quagmire Iíve been wallowing in. Letís see if I got it right. My understanding is that amisulpride would work synergistically with Mirapex, in that the amisulprideís 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 Mirapexís 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?

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. Iím concerned that my seroquel (or the Zyprexa I was previously on) is counter-productive, in that theyíre 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. Iíve tried all the usual (ambien, halcyon quit after 5 days, and I donít tolerate the anti-depressants).

1-Switch from Dexedrine to Modafinil, as it is more dopaminergic, than just a CNS stimulant (anyone have references to modafinilís 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), thatís supposed to raise dopamine levels.




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