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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by rgb on May 25, 2008, at 5:42:24
"(...) In other instances, clinically sig-
nificant apathy may not be evident until dysphoric and
vegetative symptoms have improved with antidepres-
sant treatment. Residual symptoms of motivational loss,
such as anergy, lack of drive, or lack of initiative, may
prevent return of full function after treatment of de-
pression. It is well recognized that patients with such
symptoms may benefit decisively from adding methyl-
phenidate or dextroamphetamine.31,32 (...)"Source: http://neuro.psychiatryonline.org/cgi/content/abstract/7/1/23
This utterly hits the nail on the head for me. Depression has improved with the AD, apathy and lack of real goals is still here. Ironically enough, I don't feel like jumping through the hoops and trying to find someone who would be willing to try the treatments proposed in above citation.Guess I shouldn't let this put me into the "it's the dopamine, I can't do anything" mode of thinking again since that's harmful whether it's true or not...
Posted by rgb on May 25, 2008, at 5:45:16
In reply to Interesting excerpt from this paper about apathy, posted by rgb on May 25, 2008, at 5:42:24
... but I guess it's somewhat on-topic here too ;)
Posted by undopaminergic on May 28, 2008, at 6:51:18
In reply to Interesting excerpt from this paper about apathy, posted by rgb on May 25, 2008, at 5:42:24
I've been free from the dysphoric symptoms of depression for a very long time, but the apathy has been really challenging to treat. A major problem is that it's rather difficult for an apathetic person to take the all the actions that may be needed to find effective treatment.
Posted by SLS on May 28, 2008, at 7:40:06
In reply to Re: Interesting excerpt from this paper about apathy, posted by undopaminergic on May 28, 2008, at 6:51:18
> I've been free from the dysphoric symptoms of depression for a very long time, but the apathy has been really challenging to treat. A major problem is that it's rather difficult for an apathetic person to take the all the actions that may be needed to find effective treatment.
How might Abilify affect your apathy? I was thinking that stimulating postsynaptic DA receptors plus blocking 5-HT2a receptors might offer some benefit. From what other people have told me, they become more motivated on Abilify. This is true with me as well.
- Scott
Posted by undopaminergic on May 28, 2008, at 11:05:19
In reply to Re: Interesting excerpt from this paper about apat » undopaminergic, posted by SLS on May 28, 2008, at 7:40:06
> > I've been free from the dysphoric symptoms of depression for a very long time, but the apathy has been really challenging to treat. A major problem is that it's rather difficult for an apathetic person to take the all the actions that may be needed to find effective treatment.
>
> How might Abilify affect your apathy? I was thinking that stimulating postsynaptic DA receptors plus blocking 5-HT2a receptors might offer some benefit. From what other people have told me, they become more motivated on Abilify. This is true with me as well.
>I had some really great, but intermittent, results with pramipexole, and it did improve motivation among other things. However, I had some rather dramatic side-effects too that were also intermittent: blacking out and almost losing consciousness, probably due to hypotensive attacks. Within a couple of weeks or so, all benefits were lost to tolerance, as usual. Pramipexole is probably the most anti-anhedonic agent I've ever tried, and occasionally effected a state of well-being, which was far from euphoria, but greatly enhanced enjoyment of life.
For motivation, I think sulpiride had the most powerful effect of anything I've tried, although it is rivalled by amantadine, which was effective only in one of many trials. Needless to say, tolerance eliminated most - or all (in the case of amantadine) - effects of these drugs as well.
My impression from drugs that block serotonin 5-HT2A receptors - including at least risperidone, mirtazapine and cyproheptadine - is that the results are not particularly impressive. Unfortunately, all 5-HT2A antagonists currently available clinically are very dirty drugs - it would be interesting to try some of the more selective research chemicals to better elucidate the role of this recepor.
5-HT2C-receptor antagonists, on the other hand, may be of somewhat greater interest. At some point, I may try agomelatine, or alternatively, one or more of several research compunds that are highly selective for 5-HT2C, and which have been shown to enhance VTA - but not SN - DA firing in animals.
Fortunately, my current motivational situation looks brighter than it has for a long time due to the addition of buprenorphine, and as long as its efficacy is sustained (or enhanced), the quest for new treatments to try is of diminished urgency.
Posted by iforgotmypassword on June 2, 2008, at 8:30:03
In reply to Re: Interesting excerpt from this paper about apat, posted by undopaminergic on May 28, 2008, at 11:05:19
there is a case report, or some other acedemic like documentation, detailing a male with OCD who treats his condition with psilocybe mushrooms.
the sudden 5HT2a (and 2c?) agonism of the psilocin was presumed to cause re-regulation of the receptors (down regulation?)
WHILE apparently plain 5HT2a antagonism gives some people OCD symptoms. i actually worried that i was starting to suffer from this when i was taking risperidone. i think my preexisting dyskentic and akathitic issues "evolved" to cause painful "obsession"-linked tics.
so downregulation of 5HT2a receptors is different from straight 5HT2a antagonism? (obviously i have no actual familiarity with the word "downregulation" beyond seeing it around a lot.)
---
NOW! (IMPORTANT):
i was also under the impression that 5HT2a antogonism, while techically catecolaminergic, was believed to *add* to schizophrenic cognitive difficulty, and that not just presynaptic preference but the lack of 5HT2a affinity of amisulpride that gives it's advantages in treating negative symptoms.
so what would this say about apathy specifically?
how is the syndrome of apathy defined?
Posted by rgb on June 2, 2008, at 17:44:35
In reply to 5HT2a stuff » undopaminergic, posted by iforgotmypassword on June 2, 2008, at 8:30:03
Sorry, I don't have a direct answer, but note that the psychedelic 5-HT2A agonists affect the receptor in a different way than other agonists; IIRC it's something about different conformational changes and activation of different second messengers (BTW, of which kind is serotonin? Presumably non-psychedelic, but OTOH this would be odd considering the structural similarity of serotonin and psilocin/DMT/and so on)
On a related note, I'm not sure I agree with the general idea here that 5-HT2A is bad for motivation. Psilocybin tended to induce feelings of child-like genuine fascination and meaningfulness in me. This "higher-level" effect might actually be more important than the catecholamines, don't know. Sub-psychedelic doses could possibly be useful against my current apathy, but getting this done would be such a hassle.
Posted by iforgotmypassword on June 2, 2008, at 18:28:34
In reply to Re: 5HT2a stuff » iforgotmypassword, posted by rgb on June 2, 2008, at 17:44:35
> On a related note, I'm not sure I agree with the general idea here that 5-HT2A is bad for motivation.
i meant 5HT2a *antagonism* being bad for motivation and negative symptoms, psilocin is a ("partial") agonist. i also find mushroom use emotionally rewarding. i imagine that an 5HT2a antagonist like risperidone would block the effects of psilocin.
i want to experiment further with mushrooms i have the concentration and executive drive to grow them. i am interested in both the acute effects, an the sensitization that lasts some while afterward. if the way they can help me organize inside can orient me long term (and improve my executive functioning and/or other aspects of my functioning or just in general.)
Posted by Sigismund on June 2, 2008, at 21:09:38
In reply to Re: 5HT2a stuff » rgb, posted by iforgotmypassword on June 2, 2008, at 18:28:34
There seems to be an incompatibilty between the effect of psiloscybin and OCD.
As I recall it, under the pressure of the experience, OCD type concerns are neccessarily dispensed with.
Posted by BrightEyed+Blueberry on July 4, 2008, at 13:51:32
In reply to Re: Interesting excerpt from this paper about apat, posted by undopaminergic on May 28, 2008, at 11:05:19
Can anyone send me the actual text or pdf of the full journal article, or is that a "no-no"?
Are we not allowed to post journal articles that otherwise people who don't have access to (other than the abstract) would have to pay for? Do you know? Expensive and I'm not a doctor/scientist....
Thanks,
Bright
------Interesting excerpt from this paper about apathy
Posted by rgb on May 25, 2008, at 5:42:24
Interesting excerpt from this paper about apathyPosted by rgb on May 25, 2008, at 5:42:24
"(...) In other instances, clinically sig-
nificant apathy may not be evident until dysphoric and
vegetative symptoms have improved with antidepres-
sant treatment. Residual symptoms of motivational loss,
such as anergy, lack of drive, or lack of initiative, may
prevent return of full function after treatment of de-
pression. It is well recognized that patients with such
symptoms may benefit decisively from adding methyl-
phenidate or dextroamphetamine.31,32 (...)"Source: http://neuro.psychiatryonline.org/cgi/content/abstract/7/1/23
--------------------------------------------------
> > > I've been free from the dysphoric symptoms of depression for a very long time, but the apathy has been really challenging to treat. A major problem is that it's rather difficult for an apathetic person to take the all the actions that may be needed to find effective treatment.
> >
> > How might Abilify affect your apathy? I was thinking that stimulating postsynaptic DA receptors plus blocking 5-HT2a receptors might offer some benefit. From what other people have told me, they become more motivated on Abilify. This is true with me as well.
> >
>
> I had some really great, but intermittent, results with pramipexole, and it did improve motivation among other things. However, I had some rather dramatic side-effects too that were also intermittent: blacking out and almost losing consciousness, probably due to hypotensive attacks. Within a couple of weeks or so, all benefits were lost to tolerance, as usual. Pramipexole is probably the most anti-anhedonic agent I've ever tried, and occasionally effected a state of well-being, which was far from euphoria, but greatly enhanced enjoyment of life.
>
> For motivation, I think sulpiride had the most powerful effect of anything I've tried, although it is rivalled by amantadine, which was effective only in one of many trials. Needless to say, tolerance eliminated most - or all (in the case of amantadine) - effects of these drugs as well.
>
> My impression from drugs that block serotonin 5-HT2A receptors - including at least risperidone, mirtazapine and cyproheptadine - is that the results are not particularly impressive. Unfortunately, all 5-HT2A antagonists currently available clinically are very dirty drugs - it would be interesting to try some of the more selective research chemicals to better elucidate the role of this recepor.
>
> 5-HT2C-receptor antagonists, on the other hand, may be of somewhat greater interest. At some point, I may try agomelatine, or alternatively, one or more of several research compunds that are highly selective for 5-HT2C, and which have been shown to enhance VTA - but not SN - DA firing in animals.
>
> Fortunately, my current motivational situation looks brighter than it has for a long time due to the addition of buprenorphine, and as long as its efficacy is sustained (or enhanced), the quest for new treatments to try is of diminished urgency.Interesting excerpt from this paper about apathy
Posted by rgb on May 25, 2008, at 5:42:24
"(...) In other instances, clinically sig-
nificant apathy may not be evident until dysphoric and
vegetative symptoms have improved with antidepres-
sant treatment. Residual symptoms of motivational loss,
such as anergy, lack of drive, or lack of initiative, may
prevent return of full function after treatment of de-
pression. It is well recognized that patients with such
symptoms may benefit decisively from adding methyl-
phenidate or dextroamphetamine.31,32 (...)"Source: http://neuro.psychiatryonline.org/cgi/content/abstract/7/1/23
Posted by Questionmark on August 7, 2008, at 1:02:00
In reply to Re: 5HT2a stuff, posted by Sigismund on June 2, 2008, at 21:09:38
I hope getting too off topic, but this is something i've been confused and wondering about for a good while. ...
> There seems to be an incompatibilty between the effect of psiloscybin and OCD.
>
> As I recall it, under the pressure of the experience, OCD type concerns are neccessarily dispensed with.See this was not my experience at all. If anything i feel like it was the opposite. I've only had two real experiences, but both times they were incredibly stressful and, at times, depressing because it felt like every single obsessive concern and worry i can have was going through my head one after another after another, with virtually no rest. And, although maybe much less surprising or uncommon, many things were capable of sending me into an abyss of depression and loneliness.
I'm very curious as to your thoughts on this.
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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