Posted by Adam on April 8, 2002, at 20:25:08
In reply to Re: Selegiline MAOI patch rejected by FDA » Adam, posted by Elizabeth on April 7, 2002, at 21:11:14
Hi, Elizabeth,
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>I thought that high-dose selegiline was about as effective as the other nonselective, irreversible MAOIs...That's just the point I was making. In Bodkin's Phase II study, I think the STS looks more impressive still (http://www.mhsource.com/pt/p010525.html).
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> Do you know what the ratio of oral dose to equivalent transdermal dose is?
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All the references I have seen point to a big difference. In this study, they say it's about 1:50, for instance: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9089426&dopt=Abstract
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> The rapid effect is the part that has me interested. About how fast did it work, typically? And how long did the trial last?
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I don't have any concrete numbers. The time oft quoted to me has been as little as a week for full remission. Bodkin mentions rapid onset of effect in this hearbreakingly optimistic article: http://www.news.harvard.edu/gazette/1998/12.10/depression.html
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> Why would (higher doses of transdermal selegiline lead to loss of MAO-A protection in the gut)?
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I don't know, that's just what I was told. In reality, nobody really knows how MAO-A in the gut is protected in the first place, which makes it hard to know what would cause the loss of protection at higher doses with any certainty. My guess (and this is only a guess) is that active drug exclusion (maybe P-glycoprotein or some similar culprit) keeps circulating selegiline out of the gut lining. I mean, there's obviously a directionally-selective membrane somewhere in there or lots of stuff would just leak out of you by simple osmosis. Maybe at higher doses this barrier is overwhelmed.
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> AFAIK, *no* antidepressant performs any better than any other antidepressant (overall, that is). The point of offering different options -- really different ones, not Just Another SSRI -- is to give a few more people the chance of finding something that works and is tolerable, IMO.
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Well, that's what sucks about this. I don't think selegiline is on an even footing with other AD's though, for the reasons I mentioned.
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>(The FDA is) also very corrupt, of course.
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I'm not at all disputing this, I just wonder if you know of some specific examples of this corruption, for my own curiosity.
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>I'd expect (MAOIs) to have higher success rates than the other ADs.
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The way some doctors talk, they do. However, when I read about them, I inevitably come across the statement "MAOIs are no more effective than other antidepressants..." yadda, yadda. I guess it's safest to be agnostic on that point. One might use the logic that since they seem to work for some people who are refractory to all other drugs, AND they are also likely to work for a good portion of the people who aren't so refractory, hence they are better overall. This line of thinking can't be completely right; however, I don't know how wrong it is.>There's really no reason to avoid MAOIs so desperately...unless you're addicted to banana peels.
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Well, I found my own banana-peel addiction difficult to overcome, and would hate to trivialize the plight of the banana-peel addict. However, as a recovering banana-peelaholic, I can personally say giving them up made me a better man.
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> That's not a very representative sample! I'm surprised they set it up that way -- if all the subjects are people who deliberately sought out a clinical trial, a lot of them are bound to be "treatment-resistant." The designers of the study must have known this.
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I'm speculating wildly here. However, from my own experience, and from posts I've seen on this board, it's clear that some people who entered an STS study did so because they had exhausted many other options and it was time to give an MAOI a try (the STS being a relatively pain-free way to do this). I think it's generally true that a good percentage of the people who want to get into a clinical trial do so because they've not found success with the proven options and are willing to take some risks. I imagine after Phase I and Phase II studies, when good safety info. is available, and efficacy is already demonstrated, risk aversion is diminished; a wider pool of candidates presents. Perhaps this is also a less "self-selecting" pool. Plus your n is bigger, and that certainly can lead to changes in the numbers.
poster:Adam
thread:100963
URL: http://www.dr-bob.org/babble/20020408/msgs/102437.html