Posted by psychobot5000 on January 18, 2009, at 17:06:25
In reply to Re: Atypical APs with lowest SRI - for AD augment » psychobot5000, posted by SLS on January 18, 2009, at 14:35:14
> Hi.
>
> > For my purposes (I'm looking for 5ht-2c blockade with few side-effects)
>
> How do you think that 5-HT2c blockade would be helpful?
>
> Thanks.Hi Scott,
Let me explain: I was lead here by Agomelatine. It seems to have some considerable antidepressant efficacy, which I attribute to its 5ht2c antagonism. I've taken Rozerem/ramelteon previously, which as far as I know mimics its Melatonergic effects without the 5ht2c antagonism, and not had any such positive results--and so I figure, well, maybe the 5ht2c effects are the difference.
So that's a large part of it, right there. As for the rest, Agomelatine has a short half-life. Possibly for this reason, it causes me substantial anxiety in the middle of the day (I take it once per day at bedtime). Luckily, I've found I can correct this anxiety with another drug, nefazodone (100mg), which, not concidentally, also has substantial 5ht2c antagonism. This leads me further down the path of suspecting 5ht2c as a primary mechanism of action, though I'm aware nefazodone also has other actions that complicate the picture, particularly 5ht2a antagonism. To summarize, I strongly suspect that the anxiety relief I feel from nefazodone is at least partly due to its providing supplementary 5ht2c antagonism for me, during the point in the day when Agomelatine's blood-levels are almost nonexistent. Without this supplementary medication, I feel at unpleasant degree of anxiety during this part of the day. With it, everything works out pretty well.
This idea of mine seems to be supported also by my experience with another (messy) 5ht2c antagonist, Remeron: when on that drug my mood was lowest, and anxiety highest, during the point in the day when my blood-levels of the drug were lowest. Of course, Remeron also has lots of mechanisms of action. But it does fit in.
So that's what I'm working with, and what's gotten me interested. I think 5ht2c is probably a large part of my story, especially since I don't think my low dose of nefazodone, once a day, is adequate to act very forcefully on its other targets. It seems like a solid enough hypothesis that I can work off of it, and maybe try to fine-tune it into something that works a little better, side-effect wise, etc.
Hope that answers your question. Incidentally, so far agomelatine + nefazodone = pretty awesome antidepressant combination so far. Worth a try.
Psychbot
PS: And Philippa, yes, I do like the nefazodone, at least as a low-dose augmentor--it hasn't been too sedating for me so far.
poster:psychobot5000
thread:874727
URL: http://www.dr-bob.org/babble/20090104/msgs/874803.html