Posted by jrbecker on May 11, 2003, at 10:35:28
In reply to Re: Remeron rocks for treatment-resistant unipolar » jrbecker, posted by SLS on May 11, 2003, at 9:24:35
Remeron made me feel terrible at first. The sedation was so overwhelming, that depsite an underlying sense of mood lift, the sedation itself was almost too much to take. Thankfully, this passes relatively quickly in the first couple of days and continues to decrese longitudinally over time. There is some irritability at first as well, probably due the activity at the 5HT2 receptors. This passes relatively soon as well. Longterm, anybody that has the fortitude to try and stay on it more than two months will find that most of the sedation vanishes. This is probably a fairly subjective thing though.
As for alpha-2 antagonism as a possible depressant mechanism, you might have something there. Since having a great experience with effexor as my first NE drug, I've been trying to find a comfortable fit with a drug that modulates NE, but in a more "soft" way. It is my belief that NE reuptake (or 5HT reuptake for that matter) is a pretty rough way to increase NE. Those familiar with effexor and strattera can attest to that. It's my belief that alpha-2 antagonism is a much more fine-tuned way to modulate NE release (and you get a little dopamine out of it to boot). Consequently, I've experimented with a lot of supplements (pregnenolone, dhea, etc) that modulate alpha-2 antagonism. Tx success has had mixed results from this. Take DHEA for example, although it definitely helps my mood, motivation, and energy level, I walk a fine line before it makes me irritability, anxious, and rageful -- and this is at 1-5 mg doses. Could the alpha-2 antagonism be the culprit? Quite possibly. Experiments like this have lead me to believe that I have minor bipolar tendencies and that an acute sensitivity to dopamine is an important factor in my anhedonic depression (trials with stimulants, nicotine and other supplements seem to corroborate this).
What does this mean for taking remeron? Absolutely nothing. I have had really no issues at all with anger or anxiousness or a decrease in mood for that matter. And since remeron is doing so many things biochemically at once, it's really impossible to attribute any effect to just one thing its modulating. I just know it works.
As for bipolars trying remeron, my doc said that remeron can induce mania. But in reality, this is probably a more stable drug than the SSRIs to be on. I feel very focused and calm on it. Maybe it's b/c of the 5HT2A and C antagonism -- the latter being implicated in bipolarity and the former having some sort of weak antipsychotic effect. At high doses, it's possible that the alpha-2 antagonism could trigger mania, but I believe that this is somehow being kept in check at lower doses by the 5HT 2 & 3 antagonism (and possibly by the decrese in cortisol levels). Just my own speculation though.
Back to the alpha-2 discussion. I think it's only a matter of time before they figure out an even more specific mechanism to hit for more NE modulation. For instance, I've read about one company concetrating on alpha-2c antagonism for depression. Eventually, they're gonna provide a better roadmap for these subreceptors and we'll be all the better for it.
last thing on remeron. If you're going to try it, i think you really have to be ready to spend a month ready to acclimate to it. It can be a tough go and no picnic at first. That should definitely factor into your decision.
JB
poster:jrbecker
thread:225645
URL: http://www.dr-bob.org/babble/20030505/msgs/225800.html