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.
poster:undopaminergic
thread:831008
URL: http://www.dr-bob.org/babble/neuro/20080418/msgs/831632.html