Posted by JLM on January 23, 2004, at 8:47:08
In reply to Re: What is so special about cymbalta? » jack smith, posted by maximum-doser on January 1, 2004, at 18:53:24
Once again, I feel I must reiterate a VERY important point:
According to Preskorn, who is well respected, ALL SSRI's have a flat dose response curve. So, that being the case, there is NO medically justifiable reason for anyone taking 320mgs a day. That is just plain excessive. However, the ADVERSE effects are dose dependant.
Are you seeing Ozzy Osbourne's doctor perhaps? ;0
"WHY DOES THE DROPOUT RATE FOR DRUGS WITH A SINGLE MECHANISM OF ACTION INCREASE WITH DOSE ESCALATION?
As a general rule of thumb, excessive engagement of any site of action will cause adverse effects mediated by that site of action without further increasing the magnitude of the desired effect. This appears to happen because the body can no longer compensate for the effect of the drug on that site of action and consequently adverse effects result. Take the SSIs as an example. All members of this class of antidepressants have a flat dose-antidepressant response curve. The usually effective minimum dose of each of these drugs produces 70%-80% inhibition of the serotonin uptake pump using the platelet as a surrogate marker for what is happening in the brain. Although these drugs have a flat dose-antidepressant curve, they have an ascending dose-adverse effects curve, meaning that the incidence and severity of adverse effects of these drugs increase with increasing doses even though antidepressant efficacy does not. These adverse effects include nausea, diarrhea, anxiety, and insomnia. These adverse effects appear to be produced by excessive inhibition of the same site of action that mediates the desired antidepressant response, the serotonin uptake pump."
There it is right there, from one of America's most respected psychopharmocologists.
http://www.preskorn.com/columns/9601.html?print=1
"As Preskorn pointed out, rigorous studies of the SSRIs to one another would be ideal and useful in comparing efficacy and side effects, but no such study exists or is likely to be undertaken. However, that doesn't mean these drugs' outcomes can't be compared.
In his opinion, there's a lot that can be determined based on the large number of SSRI studies that have been done. For example, he noted, the following features have generally been reported as similar across the class:
* Flat-dose antidepressant-response curves -- or the ability to produce the same average response rate at each dose above the effective, minimum dose over the dosing range;
* Equivalent antidepressant action at their usually effective therapeutic dose (however, data for fluvoxamine was not available for comparison);
* Similar efficacy when used on a maintenance basis to prevent relapse;
* The usually effective minimum dose of each produces 60 percent to 80 percent inhibition of seratonin uptake;
* All have benign adverse side effects when compared to drugs in the tricyclic class."I think the last point is starting to be something that is debated thou.
poster:JLM
thread:208072
URL: http://www.dr-bob.org/babble/20040122/msgs/304565.html