Posted by bleauberry on January 20, 2010, at 18:50:06
In reply to Surplus of SSRI receptors may lead to TRD, posted by Phillipa on January 19, 2010, at 19:07:07
Interesting find! It kind of confirms personal ideas I've had for a while.
You know how some people here, including myself, say they experience a short time of feeling really well shortly after stopping an SSRI? In my theory, it is during that time that the 5ht1 autoreceptors sense a declining serotonin presence and send signals to step up serotonin production and firing. That feels good. But then, as the feedback loops catch up, they again slow down to predetermined genetic commands. They only sped up temporarily during the serotonin drop to maintain balance.
Some of us experience feeling good the first few days on an AD, and then either get nothing or feel worse after that. In my hypothesis, it takes 3 to 4 days for the feedback loops (the autoreceptors they talked about) to sense that things have changed, and they then send commands to slow down serotonin production. So it doesn't matter that the AD is increasing serotonin, because less of it is being made...the body's genetic command to keep balance...it doesn't know that we feel bad, it is just following its genetic code.
The assumption with ADs is that they need several weeks to work. The receptors will initially shut down during the massive increase of serotonin. But, as they become adjusted to that, they will resume production and firing. In nonresponders, that probably doesn't happen...they stay shut down the whole time.
There are few drugs that have impact on the 5ht1 receptors. The ones I am aware of are:
Pindolol
Buspar
Abilify
SavellaMaybe that's why the first three have been found to be helpful in augmenting or speeding AD response.
Savella is too new for most people to know about, but several studies at pubmed have looked at its rapid action on 5ht1a as the thing that makes it unique amongst ADs. My own personal experience, I would have to agree.
As the article pointed out, norepinephrine meds can in a roundabout way accomplish the same thing. Maybe that's why I found Savella to be more potent than ECT or any previous meds...it had both NE and 5ht1 stuff going on at the same time?
Anyway, nice find Phillipa! I am in the camp that believes 5ht1 and feedback loops are big players. Merely increasing neurotransmitters in the assumption that everything else will continue working as normal is a big and flawed assumption as I see it.
poster:bleauberry
thread:934392
URL: http://www.dr-bob.org/babble/20100113/msgs/934486.html