Posted by Adam on April 11, 2002, at 18:58:44
In reply to Re: Selegiline MAOI patch rejected by FDA » Adam, posted by Elizabeth on April 10, 2002, at 11:18:01
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>(I'm not convinced that there's anything useful about the L-amphetamine metabolites of selegiline.)
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I think the possibility that they have a clinically significant effect must be allowed. There's about zero information addressing this possibility, though. However, from what I've read, it's not 100% correct to say that "l-methamphetamine is ten times less potent than d-meth" or whatever. L-meth is actually a pretty good potentiator of norepinephrine, but less so for dopamine. For this reason, it's used instead of d-meth in Vick's inhaler decongestants. However, apparently, you can get high on enough l-meth, if the anti-drug literature is any guide. I think either isoform of meth is also a weak MAOI-inhibitor. Since it's known that drugs like desipramine and reboxatine, which are pretty specific for NE-reuptake inhibition, have antidepressant effects, it's not that much of a stretch to think that l-meth couldn't have mood altering effects as well at the relevant doses.However, just as you suggest, l-meth is a mixed bag, as far as pros and cons go. Because of the reduction in metabolites when using the STS, selegiline may have significantly altered pharmacodynamics. Does this mean that it has reduced efficacy, pound for pound? I don't know. Nothing about the trials leads me to believe that, though. I always thought the changes were ultimately a plus.
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> Not off the top of my head, no. It's basically a revolving door, though: the FDA employs people who have ties to the drug industry, and people working for the FDA often move on to work in the drug industry.
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The whole drug-approval process is rife with conflicts of interest. A very significant number of trials are run by investigators who have a financial stake in the companies producing the drug or other therapy. I wonder if a corrupt investigator running a trial would be cancelled out by a corrupt regulator on a competator's meal ticket. It would be nice to get rid of all these conflicts of interest. I'm not sure there would be anyone left to do the work, though.
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> I don't doubt it. Of course, I've been in that situation and I was never willing to take the risk! (The risk I was worried about was the risk of being stuck in the placebo arm, not the risk of adverse effects. Also, a lot of the time, the researchers require you to be off all other medications in order to participate in a clinical trial.)
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The thing that hooked me into the STS trial was the promise, after completing the six-week blinded portion, of six months on the 20mg patch. It was a suprisingly tough six weeks, but I could see how such a promise kept others like myself going. I have wondered quite often what such an incentive might do to the "placebo effect". There's been recent work published suggesting a good portion of the placebo effect can be chalked up to the patient's willingness to please the doctor. Is one more or less willing when the promise of the real thing awaits? And do people who know they are now getting the real thing suddenly respond, even when they were getting the real thing all along?I'm very interested in seeing the results of all the studies. I'll be waiting with interest.
poster:Adam
thread:100963
URL: http://www.dr-bob.org/babble/20020408/msgs/102803.html