Posted by Adam on March 17, 2001, at 22:24:14
In reply to Re: Report of success: Selegiline: alernate MAOI, posted by Mr. Scott on March 16, 2001, at 17:14:17
> Do you think there is a "SAFE" dosage to take selegeline WITH an SSRI?
In theory, there shouldn't be a problem with doses where there is no inhibition of MAO-A, which one would think is 10mg or lower. From what I've read, there is complete or near-complete inhibition of MAO-B at doses around 5mg/day, and once you are up in the 10mg/day range, you've got complete inhibition of MAO-B, and a small amount of inhibition of MAO-A. You have to be mindful of the fact that the "specificity" of selegiline is really just a differential affinity for each isoform of MAO. Most dose-response curves for drugs are typically "sigmoidal", or S-shaped (and can be fit "parametrically" pretty well, in most cases, to the "Hill equation", though there are usually better models for specific drugs). You have a long range on the low and high ends of the curve where there is little or no added effect for an increase in dose, and then somewhere in between the effect shoots up, and in this dose range, you get a near linear increase of effect per increase in dose. So you want to know, what's the real EC50 (the dose where 50% of inhibition occurs) for MAO-A? That dose is one you want to stay away from, because anything close to that (within about a log or half a log), or much higher, could give you a pretty significant inhibition of MAO-A. The trouble is, I'm not sure if the answer to that is known. If someone has done a dose response curve for MAO-A in people, I'm not aware of it, and there's little real information for someone to work with to inform such a decision (to augment an SSRI with selegiline or visa versa), if there is no such info. And, unfortunately, that value (EC50 for MAO-A) could vary quite a lot from person to person, perhaps because they are taking a drug that inhibits selegiline metabolism, or they are deficient in a drug-metabolizing enzyme (neither of which may be easy to ascertain).
I was once under the impression that, at 5mg/day selegiline, one should have no problem taking an SSRI concurrently, and you would still see complete or near-complete inhibition of MAO-B. I've revised my thinking, especially since I've been experimenting with small-molecule drugs a lot a work, and seen some of the variation that can occur in dosing, even among inbred animals. It may be entirely possible (and I know some people do it, as there are a few papers from Europe describing the practice) to take low-dose selegiline and an SSRI concurrently, and suffer no ill effects. However, there may be real risk, which is impossible, as far as I can see, to assess beforehand, of serotonin syndrome, which, as we all know, could be deadly. Given even remote odds, I seriously doubt you will find a physician on American soil who would go along with the experiment. Maybe I'm wrong, but, given the risks, I don't think this is a viable approach, for both health and legal reasons.
poster:Adam
thread:56408
URL: http://www.dr-bob.org/babble/20010310/msgs/56813.html