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Re: RLS, Akathisia + Dopamine D-2 receptors? Larry Hoover

Posted by cache-monkey on April 14, 2007, at 17:14:00

In reply to Re: RLS, Akathisia + Dopamine D-2 receptors? cache-monkey, posted by Larry Hoover on April 13, 2007, at 7:03:23

Wow. Larry, thank you so much for all of the thought you put into your response. It is very much appreciated

<< The important thing to conclude is that you do ot have a definitive answer, IMHO. Your bodily response, from an observational perspective, is ambiguous. Your desire to have it understood may not be satisfied. >>

You've kind of hit the nail on the head here. I guess on some level I realize that this isn't something that can be fully reasoned out. But, given the state of constant anxiety and agitation I'm in, I head toward the obsessional. And also, it's becoming really frustrating not having such non-specific symptoms (especially the physical ones that include pain flares and allergies to multiple meds). I don't have a functional diagnosis other than BP-NOS, which has become a catch-all for "well, we really don't know what's wrong with you so we'll call it BP". It's getting quite scary not to have a well-defined set of treatment options ahead of me.

<< The functional import part I think you're fully prepared for: management. Above all, for you, med trials should include very slow dose titration, starting well below normal therapeutic doses. You are especially sensitive. >>

Yeah, that's about right. This only adds to the frustration. I suppose this is something that I can concentrate on with my therapist.

<< I'm an empiricist. Seeman is seeking a mechanistic "proof" of a fully-observed phenomenon, the empirical evidence. What isn't known, and can't be proven from his work, is the time course of that conversion reaction. Does it remit? Who knows. >>

I'm not sure that I agree with you here. One could argue that the work that he's been doing on dopamine supersensitivity (DA-SS) is that it elucidates a common mechanism in a number of psychotic/activated states. This could potentially lead to treatments for DA-SS (e.g. one paper by Seeman on reversing it through general anaesthesia). That being said, his research line right now isn't really geared toward clincal treatment.

<< That doesn't make it unmanageable, in any case. Doing management experiments (including slow/low dose titrations) will obtain further empirical evidence. No amount of thinking will provide similar "proof". >>

Again, thanks for bringing this point home. It's frustrating for me to hear, but you're absolutely right in that I can't think my way out of this. In fact, trying to do so is probably ultimately unproductive. However, I think some amount of deductive reasoning is valuable in trying to narrow down the set of medications a bit.

FWIW, my current trajectory is to first switch from Klonpin to Valium, as I seem to have become mildly allergic to the former. (Or maybe I always have been and this has led to my other allerrgic responses.) And then the following meds are in the bullpen...

1) Memantine (possibly useful for agitation, might prevent further DA-SS)

2 An SSRI. I've only tried Celexa and Lexapro so far. And out of all med combinations I only felt close to stable on Celexa+Wellbutrin, and on more recently on Tegretol before I went allergic. Common mechanisms between the Celexa and Tegretol are blocking of L-type calcium channels and (probably) an increase in allopregnanolone. I'm debating between retrialing Celexa or trying Zoloft. The latter doesn't seem to have the calcium channel actions, but likely has stronger effects on allopregnanolone and hasn't been explictly been shown to increase the expression of D-2 receptors. But, with some sort of BP diagnosis, any SSRI is a little dangerous. So low and slow here regardless.

3) Dynacirc/isradipine. I actually benefitted a little bit from 120 mg / day of IR verapamil, but went allergic. L-type calcium channel blocking seems to be a common element in my few positive med experiences. So hopefully after a switch off of klonopin, I'll actually not go allergic.

Anyway, I think I'm writing this list for my own benefit. Clearly it's a bit more overthinking on my part. Hopefully with it written down somewhere (and maybe printed out to look at) I can obsess a little bit less. But, if anyone happens to want to chime in, that's fine too.

Thanks again, Larry.




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