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Dr. Bob is Robert Hsiung, MD,
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Posted by cache-monkey on December 20, 2004, at 13:27:59
Hey folks,
I started BuSpar a while ago and I've never been quite clear as to what it's doing for me. I feel like certain cognitive aspects of my anxiety/depression have been a little diminished, although my response to low doses of Lamictal so far trump even that.
But I feel that BuSpar might also be increasing other aspects of my anxiety. Particularly the physical ones (e.g. heart palpatations, tightness in my head/chest, etc.). Anyone else experience this?
Also, I'm wondering if this has anything to do with the alpha-2 andrenoreceptor antagonism of 1-PP, the primary buspirone metabolite. I don't really know what alpha-2 antagonism does, but I'm pretty sure that I don't react well to things that mess with my NE system. Also, I'm an intermediate to poor in my CYP-2D6 metabolism. Since 2D6 is responsible for clearance of 1-PP, maybe I've got too much of the 1-PP in my system. Any thoughts on this idea?
Thanks,
cache-monkey
Posted by linkadge on December 20, 2004, at 14:09:52
In reply to BuSpar = increased anxiety? (alpha-2 antag.?), posted by cache-monkey on December 20, 2004, at 13:27:59
the alpa-2 antagonistm will increase overall norepenephrine release. This could increase anxiety in the same way that mirtazapine and yohimbine can increase anxiety (ie phyiscal symptoms) It might also increase anticipatory anxiety.
Linkadge
Posted by olysi79 on December 20, 2004, at 16:57:34
In reply to Re: BuSpar = increased anxiety? (alpha-2 antag.?), posted by linkadge on December 20, 2004, at 14:09:52
Buspar is a frustrating medication. It can ause anxiety for two reasons, the first being exactly what Linkadge said. Second is that is can block Dopamine and cause akathisia. I had something wierd happen to me when I tried Buspar for a second time... I went into an episode of agitation and depression... at first I thought that it was typical old akathisia, but my pdoc thinks otherwise. No one is really sure how this med works, and on top of that, it doesn't work very well. Perhaps you should ask to try something different.
> the alpa-2 antagonistm will increase overall norepenephrine release. This could increase anxiety in the same way that mirtazapine and yohimbine can increase anxiety (ie phyiscal symptoms) It might also increase anticipatory anxiety.
>
> Linkadge
Posted by cache-monkey on December 20, 2004, at 18:23:06
In reply to Re: BuSpar = increased anxiety? (alpha-2 antag.?), posted by linkadge on December 20, 2004, at 14:09:52
" the alpa-2 antagonistm will increase overall norepenephrine release. This could increase anxiety in the same way that mirtazapine and yohimbine can increase anxiety (ie phyiscal symptoms) It might also increase anticipatory anxiety. "
Thanks, Linkadge. Is this because blocking the alpha-2 receptors means more free-floating NE? Or does it trigger additional synthesis?
cache-monkey
Posted by cache-monkey on December 20, 2004, at 18:29:32
In reply to Re: BuSpar = increased anxiety? (alpha-2 antag.?), posted by olysi79 on December 20, 2004, at 16:57:34
"Buspar is a frustrating medication. It can ause anxiety for two reasons, the first being exactly what Linkadge said. Second is that is can block Dopamine and cause akathisia. I had something wierd happen to me when I tried Buspar for a second time... I went into an episode of agitation and depression... at first I thought that it was typical old akathisia, but my pdoc thinks otherwise. No one is really sure how this med works, and on top of that, it doesn't work very well. Perhaps you should ask to try something different."
Hmm. I didn't think that BuSpar typically reduced dopamine; I remember reading somewhere that it acutally increases DA somehow... But, I did experience quite a bit of jitteriness when I first started it. That went away, but nowadays my physical and mental tension/anxiety seems to come creeping up about half and hour after dosing BuSpar and then slowly dminish.
I agree that it's probably not the best drug for me. My pdoc (for a variety of reasons) started me on a trial of Lamictal that seems to be actually working right now. Hopefully it continues to do so. As far as the BuSpar, I'm on a small dose (7.5 mg/day having reduced from 10 mg), but my pdoc wants me to keep it constant so we can sort out what the Lamictal's doing. I'm actually tempted to reduce a tad further (to 5 mg/day), anyway...
Anyway, I'm just rambling now. Sorry to hear that your second round with BuSpar was so bad. If it wasn't akathisia, what does your pdoc think it was?
Best,
cache-monkey
Posted by linkadge on December 20, 2004, at 20:05:13
In reply to Re: BuSpar = increased anxiety? (alpha-2 antag.?) » olysi79, posted by cache-monkey on December 20, 2004, at 18:29:32
Buspar acts as a bit of an antagonist at the dopamine d2 receptors. But on the other hand it will increase DA in the frontal cortex via activation of the 5-ht1a receptors.
The alpha-2 autoreceptors act as an inhibitory thermostat on NE release. Ie when the receptors get activated, they turn down the firing rate of norepinephrine.
Linkadge
Posted by PeterJ on December 21, 2004, at 23:45:44
In reply to BuSpar = increased anxiety? (alpha-2 antag.?), posted by cache-monkey on December 20, 2004, at 13:27:59
> But I feel that BuSpar might also be increasing other aspects of my anxiety. Particularly the physical ones (e.g. heart palpatations, tightness in my head/chest, etc.). Anyone else experience this?
I experienced something similar using Buspirone about 15 years ago.
> Also, I'm wondering if this has anything to do with the alpha-2 andrenoreceptor antagonism of 1-PP, the primary buspirone metabolite. I don't really know what alpha-2 antagonism does, but I'm pretty sure that I don't react well to things that mess with my NE system. Also, I'm an intermediate to poor in my CYP-2D6 metabolism. Since 2D6 is responsible for clearance of 1-PP, maybe I've got too much of the 1-PP in my system. Any thoughts on this idea?
Your idea makes sense to me. I had the same idea at the time I took buspirone. It could be a combination of a higher level of CYP-3A4 (producing the 1-PP) and/or lower levels of CYP-2D6 (metabolizing the 1-PP) and/or a greater sensitivity to alpha-2 antaogonists.
Based on this hypothesis, I tried clonidine (an alpha-2 agonist) combined with buspirone and got very good anxiolytic results. After a few months the effects faded but it was good while it lasted. How much of the benefit was the direct anxiolytic effect of the clondine and how much was the clonidine preventing buspirone side effects is something I can't be sure about. But I know the buspirone was very anxiogenic until the clonidine was added.
Some other observations: The anxiety I experience with buspirone was delayed in onset by a few days and gradually worsened the longer I took buspirone alone, consistent with the effect of a metabolite. On another occassion I experienced side effects from mCPP which is a similar metabolite of trazodone. I also experienced anxiety from mirtazepine, which is also an alpha-2 antagonist.
By the way, I was interested enough in the effects of these metabolites that I did some research on a metabolite of risperidone (which I had not taken) and got it published in a medical journal.
PeterJ
Posted by ed_uk on December 22, 2004, at 5:36:19
In reply to Re: BuSpar = increased anxiety? (alpha-2 antag.?), posted by PeterJ on December 21, 2004, at 23:45:44
Hi!
>By the way, I was interested enough in the effects of these metabolites that I did some research on a metabolite of risperidone (which I had not taken) and got it published in a medical journal.
I am impressed! Are you a pharmacologist?
Ed.
Posted by ed_uk on December 22, 2004, at 5:37:43
In reply to Re: BuSpar = increased anxiety? (alpha-2 antag.?), posted by PeterJ on December 21, 2004, at 23:45:44
Has anyone else obtained a good anxiolytic effect by combining buspirone with clonidine?
Ed.
Posted by PeterJ on December 22, 2004, at 20:36:39
In reply to Re: BuSpar = increased anxiety? (alpha-2 antag.?) » PeterJ, posted by ed_uk on December 22, 2004, at 5:36:19
> I am impressed! Are you a pharmacologist?
I have a degree in Biochemistry. I've had so many unusual medical problems myself that I'm running about even in the number of articles about me in the medical literature vs the number of articles by me. I'd prefer it was more of the latter. I'm sure you know the Chinese curse, "may you live in interesting times." The Psycho-Babbble equivalent could be "may you be an interesting case."
PeterJ
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